SYSTEMS NEUROBIOLOGY

Winter/Spring Term 2015

MSNBIO 2102 (NROSCI 2102)

BLOCK 1

GENERAL NERVOUS SYSTEM ORGANIZATION

and

Course Information

2

Systems Neurobiology MSNBIO 2102 (NROSCI 2102)

Course Information

General Information Systems Neurobiology is a graduate course that is designed to introduce the student to structure-function relationships in the central and peripheral nervous system. The course emphasizes the anatomical organization of neural systems and draws information from texts and original scientific literature. Information relevant to humans and to experimental animals will be covered. The course is divided into four blocks: General Nervous System Organization, Sensory Systems, Motor Systems and Integration of Behavioral, Autonomic and Endocrine Functions. The course has an overall director and four block leaders who are responsible for the organization and implementation of the lectures, laboratories, conferences and exams. Students should contact Dr. Simons if they have particular questions or problems regarding overall course organization. Individual block leaders should be contacted if problems arise that are specifically related to lectures, laboratories, conferences or exams of a particular block. Course Director: Dr. Daniel Simons Dept. Neurobiology 648-9442 BST E1452

cortex@pitt.edu Block 1 Leader: Dr. Simons Block 2 Leader: Dr. Simons Block 3 Leader: Dr. Robert Turner Dept Neurobiology, BST3 4074 rturner@pitt.edu Block 4 Leader: Dr. Linda Rinaman Dept. Neuroscience 624-6994 CRWFRD 446

rinaman@pitt.edu Teaching assistant: Greg Wojaczynski gjw13@pitt.edu

3

Exams and Grading Policy

There will be four exams, each covering material from a specific block. Each exam in Blocks II-IV is worth 100 points. For Block I, there is an exam (85 points) and one quiz (15) points. It is important to understand that the nervous system functions as an integrated organ; organization and function build upon basic concepts that are taught during all blocks of the course. Thus, you should expect that material taught in one block may be covered at a different level in other blocks and would appear on the exams. Exams are designed to be completed in two hours. Brain material will be used in the laboratory; for exams, slides and photocopies of slides will be used in the lecture rooms for anatomy questions. Both short answer and short essay questions will be used to a varying extent for each exam. Each block counts towards 25% of the final grade.

Students who perform poorly on exams, and thus may be in danger of receiving a low grade for the course, will be notified by the course director. Appropriate interventions to help students who are having difficulties with the material will be discussed.

The exams will include questions that test knowledge of information provided by each lecturer, including material described in the handouts. When there is conflicting information between information provided by the lecturer and a suggested reading, students are encouraged to contact the lecturer for clarification. At a minimum, you should assume that the information provided by the lecturer is accurate and will be used for exams.

Students are expected to take the exam at the scheduled time. If unanticipated circumstances (illness of student or family member) arise, please contact the Block Director or Dr. Simons as soon as possible so that an examination time can be rescheduled. Students will receive a zero for the exam if the appropriate faculty director is not contacted before the exam. Students must take all exams and the quizz.

University of Pittsburgh policies regarding add/drop, withdraw and incompletes will be followed. Students with Disabilities Students with special needs regarding lectures, laboratories or exams should meet with Dr. Simons to discuss their particular situation and needs. If you have a disability for which you are or may be requesting accommodation,

4

you are also encouraged to contact Disability Resources and Services, 216 William Pitt Union, (412) 648-7890/(412) 383-7355 (TTY), as early as possible in the term. DRS ill verify your disability and determine reasonable accommodations for this course. A comprehensive description of the services of that office can be obtained at www.drs.pitt.edu. Course Materials: Textbooks Required: DeArmond, Fusco, Dewey: Structure of the Human Brain: 3rd Ed. Oxford

University Press, 1989. NOTE: THIS IS A DIFFERENT ATLAS THAN USED PREVIOUSLY Optional : Zigmond, Bloom, Landis, Roberts, Squire: Fundamental Neuroscience, 1st

or 2nd edition, Academic Press, 1998

Kandel, Schwartz, Jessell: Principles of Neural Science, 4th edition, McGraw-Hill, 1999

Texts can be purchased at the University book store. Also, two copies of each text book are on reserve in Falk and Langley libraries. The atlas is not on reserve and therefore should be purchased; the atlas is the only required text for the course. Suggested Readings: Faculty lecturers have provided suggested readings that may help you gain the background that is necessary to follow lectures. These readings also may help you consolidate and review the material covered in different lectures. Exam questions will be based on the information provided by the lecturers and the handouts, not the suggested readings unless specifically noted by the lecturer. Course Website All lecture handouts and Powerpoint presentations are posted on the course website: http://simonslab.neurobio.pitt.edu/snc/. Materials from last year's course are stored there for your use. The material will be updated just prior to or shortly after each lecture.

5

Grey Matter on My Mind Dr. George Carvell of the Department of Physical Therapy has created an excellent computer-based instruction program for neuroscientists. It can be accessed free of charge by anyone with a University of Pittsburgh computer account. Using your Web browser, go to https://www.gmomm.pitt.edu (make sure you enter the “s” after http). When prompted, enter your Pitt email userid and password, the same as you use for your Pitt email account. For non-Pitt students, please contact Dr. Carvell at gcarvell@pitt.edu to set up an account.

You need ShockWave Player, FlashPlayer, QuickTime and Adobe Reader. Set

Internet Explorer (or other Web browser) to Aallow pop-ups from this source@ (note: you

may have to re-boot your computer to set this up). For viewing movies, if you click on the option in the movie player to view the movie using Windows Media, you can set the preference for looping (continually replaying) the movie clip; this is quite useful. Note that the program prevents you from printing any of the material. Also, the QuickTime Virtual Reality movies won’t run from the web.

At the start of GMOMM, you can choose to either start the program or go directly

to a searchable index (GMMOMWEBwssearch.pdf). The index is also accessible from the Home page at program start-up. Note that you can skip the introductory movie clip on the home page by moving the mouse to the lower left.

GMOMM is quite comprehensive and good fun, too. The Study Buddies are

particularly helpful as tests of your knowledge. Enjoy!

Self-Study Exercises

Each student will be provided with a collection of self-study exercises that are intended to facilitate learning details of the anatomical organization of functional systems. These are provided as material for each student to utilize outside of the laboratory. Self-study exercises will not be graded or tested. Laboratories

Laboratory exercises are designed to supplement the information you gain from lectures, handouts and readings. Neuroanatomy is a visual science, and the exercise of visualizing structures in three dimensions helps integrate organizing principles of the functional systems. Unless specified, all laboratories will take place in Scaife Hall, 3rd floor teaching laboratories. Each student will receive a coded card for access to the laboratory. All cards must be returned to Dr. Simons at the time of the Block IV exam or before final grade rosters are completed.

6

Specific laboratory rules will be strictly enforced. Dr. Simons will review laboratory procedures at the beginning of the course. Failure to comply may result in expulsion from the course.

1. Under no circumstances should any material be removed from the laboratory.

2. Gloves must always be worn when examining wet brain specimens. This applies to material that is enclosed in plastic bags; bags are known to leak! .

3. Specimens should not be moved from their designated stations on the laboratory bench.

4. Specimens are used in subsequent years. Consequently, extreme care should be exercised when handling each specimen. 'Scrap' specimens are available from the teaching assistants for dissection.

5.Keep all wet tissue specimens moist with paper towels during the laboratories and return them to their designated container when you have completed the laboratory exercise. 6. YOU MUST CLEAN UP AFTER YOU ARE FINISHED. WIPE UP ANY SPILLS AND THROW AWAY DISPOSABLES IN APPROPRIATE CONTAINERS. 7. No food or drink is allowed in the laboratory

7

Course Schedule

MSNBIO/NROSCI 2102 Systems Neurobiology Course 2015

Monday, Wednesday,: 9-10:20 am Friday: 9-11:50 am Lectures/Exams in Victoria 230. BLOCK I: General Nervous System Organization WEEK 1

Monday January 5 Intro. Brain Structure Dr. Simons Wednesday January 7 Gross Brain Laboratory 3rd Fl Scaife Lab Friday January 9 Gross Brain Lab (cont) 3rd Fl Scaife Lab

WEEK 2

Monday January 12 Neural Circuits Dr. Simons Wednesday January 14 Thalamocortical Relations Dr. Simons Friday January 16 Vascular System and Spinal Cord Laboratories 3rd Fl Scaife Lab

WEEK 3

Monday January 19 > Martin Luther King, Jr. Day: No Classes > Wednesday January 22 Monoaminergic Systems Dr. Sesack Friday January 24 LAB QUIZ & SC/Brainstem Lecture Dr. Simons 3rd Fl Scaife Lab WEEK 4 Monday January 27 Imaging & Functional Anatomy Dr. Halquist Wednesday January 29 Brainstem Lab (cont.) 3rd Fl Scaife Lab Friday January 31 Forebrain Laboratory 3rd Fl Scaife Lab BLOCK 2: Sensory Systems

WEEK 5 Monday February 2 Taste and Olfaction Dr. Kandler Wednesday February 4 Vision 1 Dr. Simons Friday February 6 Block 1 Exam (9:00-11:00 am)

WEEK 6

Monday February 9 Vision 2 Dr. Simons Wednesday February 11 Visuomotor/Spatial Cognition Dr. Olson Friday February 12 Vestibular System Dr. Yates

WEEK 7

Monday February 16 Auditory System 1 Dr. Kandler

8

Wednesday February 18 Auditory System 2 Dr. Kandler Friday February 20 Systems Plasticity Dr. Kandler

WEEK 8

Monday February 23 Somatosensory 1 Dr. Simons Wednesday February 25 Somatosensory 2 Dr. Simons

Friday February 27 Motor Units &Muscle Receptor* Dr. Yates * 1st lecture for Motor Block BLOCK 3: Motor System WEEK 9

Monday March 2 Somatosensory 3* Dr. Simons * Last lecture for Sensory Block

Wednesday March 5 Spinal/Brainstem Control Mech.1 Dr. Yates Friday March 7 BLOCK 2 EXAM

>>>>>>>>>>>>>>> Spring Recess <<<<<<<<<<<<<<<<< WEEK 10

Monday March 16 Elements of Motor Behavior Dr. Strick

Wednesday March 18 Cortical Control of Movement Dr. Strick

Friday March 20 Cerebellum Dr. Strick

WEEK 11

Monday March 23 Basal Ganglia Dr. Strick

Wednesday March 25 Central Pattern Generation and Descending Pathways Dr. Turner

Friday March 27 Oculomotor system Dr. Gandhi BLOCK 4: Integration of Behavioral, Autonomic, and Endocrine Functions WEEK 12

Monday March 30 Hypothalamus Dr. Card Wednesday April 1 Behavioral State Dr.Card

Friday April 3 BLOCK 3 EXAM WEEK 13

Monday April 6 Neuroendocrine System Dr. Sved Wednesday April 8 Autonomic Nervous System Dr. Rinaman

Friday April 10 Limbic system, reward Dr. Dong WEEK 14

Monday April 13 Stress/emotional learning Dr. Rinaman Wednesday April 15 Hippocampus Dr. Barrionuevo

Friday April 17 PFC and Executive Control Dr. Sesack Wednesday April 22 BLOCK 4 EXAM

9

LABORATORY EXERCISE 1

Neuroembryology and Major Structures of the Central Nervous System INTRODUCTION

There are several segments to this laboratory exercise. The first portion will

introduce you to the overall structure of the nervous system, some general principles underlying its organization, and some basic nomenclature which will allow you to "find your way around" the brain throughout the rest of the course. Begin by familiarizing yourself with the terminology of anatomical relationships from lecture. Chapter 2 in the Zigmond et al. textbook provides a brief but useful introduction to the major structural organization of the brain and illustrations of standard section planes and terminology.

In this and subsequent laboratory exercises, you should make full use of the gross brain specimens available to each laboratory group. At the end of today's exercise, you should be able to:

1) identify the major parts of the brain and match them with the embryonic brain vesicle from which they were derived 2) delineate on a gross specimen the approximate boundaries of the five lobes of the cerebral cortex and provide a brief description of their functions 3) describe the relationship between the meninges and components of the blood supply including arteries, veins and venous sinuses 4) identify important subdivisions of the brain including the thalamus, hypothalamus, basal ganglia, and cerebellum. 5) identify the cranial nerves and their functions (columns 1 and 4 in Table at end of exercise).

NEUROEMBRYOLOGY

The nervous system has its origins in a thickening of tissue along the dorsal surface

of the embryonic ectoderm called the neural plate. A midline groove develops in the neural plate, and tissue on either side expands dorsally to fuse and form an embryonic neural tube. By the 24th day of gestation, a fundamental organizational plan is already evident: Cells destined to form the peripheral nervous system have become segregated as the neural crest; the closure of the neural folds to form a longitudinal tube is virtually complete; and the rostral end of the neural tube, which will form the future brain, is beginning to exhibit a number of bulges and flexures. Within the neural tube itself the proliferative zone in the tube's ependymal lining has become demarcated into two regions by the sulcus limitans; these are a dorsal alar plate and a ventral basal plate, from which respectively the sensory and motor components of the spinal cord and brainstem will be derived.

10

By the fifth week of gestation in humans, the embryonic nervous system has differentiated into four major parts, the forebrain or prosencephalon, the midbrain or mesencephalon, the hindbrain or rhombencephalon and the embryonic spinal cord (see Introductory Lecture). The prosencephalon is separated from the mesencephalon by the cephalic flexure. More caudally, the rhombencephalon has formed, and this will further differentiate into two brain vesicles, the myelencephalon (later to become the medulla) and the metencephalon (the embryonic pons). The remainder of the neural tube constitutes the embryonic spinal cord. Because the rate of growth of the neural tube is so much greater than that of other embryonic structures, as the brain continues to develop, additional flexures will further modify the original tubular structure of the neural tube, though the basic organization described here will be retained. Similarly, the lumen of the embryonic neural tube will expand and change shape to form large spaces, called ventricles, filled with cerebral spinal fluid. What is the ventral, motor component of the embryonic spinal cord called? _____________________ ____________(1) What sulcus separates it from the sensory part? __________________________________(2)

THE PROSENCEPHALON

The prosencephalon, the rostral-most part of the neural tube, will undergo a tremendous expansion and differentiation during the remainder of gestation and into infancy. You can get some idea of the extensiveness of this expansive growth by locating the lamina terminalis in the hemisected brain, using Atlas Figure 4 as a guide. This represents the rostral limits of the original neural tube, and the great mass of tissue rostral to it in the adult brain was formed during the growth of the embryonic prosencephalon. As you will see in later exercises, many telencephalic structures are "arc" shaped in the adult brain. This characteristic shape results from the anterior, posterior and inferior expansion of the cerebral hemispheres during ontogeny. The prosencephalon's principle homologue in the adult nervous system is the telencephalon and the diencephalon. The Telencephalon

Important tissue masses derived from the telencephalon are the cerebral hemispheres. These structures reach their greatest functional development in higher mammals and are usually the brain's most striking component, enveloping virtually the entire dorsal and lateral surfaces as well as a significant amount of the brain's ventral aspect. The hemispheres are paired structures separated from one another on the midline by the longitudinal fissure.

The visible part of the cerebral hemisphere is called the cerebral cortex, which

consists of a thin (approximately 1.5 to 2.5mm) sheet of neurons and underlying axons. The cerebral hemispheres of the adult brain exhibit numerous rounded convolutions or gyri separated by fissures or sulci. During early stages of neurogenesis the surface of the hemispheres is smooth and only later becomes convoluted. This infolding greatly

11

increases the surface area of the cortical sheet within the limited confines of the cranial vault. Some of the first sulci to develop will later attain significance in the adult brain as landmarks dividing the cerebral cortex into large regions called lobes. Examination of a brain at 6 months reveals a central or Rolandic sulcus which demarcates the frontal lobe anteriorly from the parietal lobe, a parieto-occipital sulcus which divides the parietal lobe from the occipital lobe posteriorly, and a large lateral sulcus or Sylvian fissure which separates the temporal lobe ventrally from the rest of the cerebral cortex. Using Atlas Figures 1 and 2 as a guide, identify these important sulci and the approximate boundaries of the frontal, parietal, occipital and temporal lobes on a gross brain specimen. Buried within the lateral sulcus is a fifth major lobe called the Insula. An illustration of how the insula is "overgrown" by the other, hemispheric lobes can be found in horizontal brain sections (for example, Atlas Figures 10-16). Finally, examine the ventral surface of the brain (Atlas Figure 3) and observe how the cortex of the frontal and temporal lobes cover a good deal of the brain's ventral surface. What lobe is anterior to the central sulcus? ____________________________(3) What lobe is posterior to the parieto-occipital sulcus? ________________(4)

The Cerebral Cortex. Functionally, the cerebral cortex can be divided into three kinds of areas. First, neurons in what are known as primary sensory areas receive information from visual, auditory, vestibular, somatosensory, gustatory and olfactory receptors in the periphery. Second, there are areas of motor control which are involved with the initiation of movements. Third, there are associative or integrative areas of cortex which are involved in so-called "higher" processes such as language, learning and memory, and sensorimotor integration. One (or a few) general functions are ascribed to each of the five lobes of the cerebral cortex (frontal, parietal, occipital, temporal and insular). For example, the frontal lobe has a major role in initiating voluntary movements, whereas the occipital lobe is important for processing visual information. Nevertheless, each lobe can be partitioned into a number of anatomical subdivisions, each having its own functional attributes, so that the association of a single function with an anatomically defined lobe is at best only a useful rule of thumb.

Within a cortical hemisphere, short and long fiber tracts interconnect areas performing interrelated functions, for example vision (occipital lobe) and eye movement (frontal lobe). Also regions within the left and right hemisphere are connected by a thick band of horizontally running axons called the corpus callosum. Locate the corpus callosum by gently separating the hemispheres of a whole gross brain and looking down into the longitudinal fissure. Identify it also in horizontal brain sections and in a hemisected brain (see also Atlas Figure 4)

The frontal lobe. The frontal lobe is the part of the cerebral cortex which lies anterior to the central sulcus. Use Atlas Figures 1 and 2 to locate the anterior part of its lateral surface which is divided into three longitudinal strips oriented from rostral to caudal, called the superior, middle, and inferior frontal gyri. This part of the frontal lobe subserves diverse functions. Damage to it can result in a condition known as frontal-lobe syndrome. The patient shows deficits in eye movements and often striking

12

changes in personality. The patient may become impulsive and flippant, and display a loss of social decorum. On the inferior surface of the brain are the orbital gyri of the frontal lobe, so named because they are located just above the skull's bony orbits.

A functional area of major importance in the frontal lobe is the precentral gyrus, which, on the lateral surface, runs across the posterior part of the frontal lobe from medial to lateral. This part of the cortex is called the somatomotor cortex because it controls volitional movements of the contralateral body. Neurons located within adjacent areas of this gyrus project to motoneurons at different levels of the spinal cord, and control different, nearby muscle groups. Medial aspects of the precentral gyrus control movements of the leg, whereas progressively more lateral parts of the gyrus control movements of the trunk, arm and face. Thus, the precentral gyrus contains a functional 'map' of the contralateral body and is described as being 'topographically' organized. What fiber tract interconnects motor cortex in the right and left hemispheres? _______________ ______________________(5)

In the left hemisphere of most individuals, the part of the inferior frontal gyrus just anterior to the precentral gyrus has a special motor-related function. This is Broca's area, a part of the brain that is critically involved with the motor components of speech. Patients with damage here have difficulty producing words, and their speech may be hesitant and non-fluent. A language deficit is called 'aphasia'. Locate Broca's area on Atlas Figure 2 (where it is designated as inferior frontal gyrus, triangular part and opercular part) and on a gross specimen. Which side of the body receives motor commands from the left precentral gyrus? ____________________(6)

What does it mean to say that motor cortex is topographically organized? _______________________________(7) Where in the precentral gyrus is the leg represented? __________ ______________________(8) What part of the frontal lobe is concerned with control of the motor components of speech? _______________________(9) With emotional reactivity and personality? _____________________(10)

The parietal lobe. The parietal lobe is bounded anteriorly by the central sulcus. The first gyrus behind the central sulcus is the postcentral gyrus. In order to find the central sulcus, examine the lateral surface of a gross brain specimen and note that the rostral half of the cerebral hemisphere consists of three longitudinally oriented gyri (the superior, middle and inferior frontal gyri) and two gyri oriented mediolaterally, at a right angle to them. The latter are the pre- and postcentral gyri, and the sulcus between them is the central sulcus. The postcentral gyrus contains somatosensory cortex, so called because neurons here receive information from somatic sensory receptors in skin and from proprioceptive sensory receptors in muscles and joints. Like the motor cortex, the somatosensory cortex is topographically organized; again, the contralateral leg is represented medially, whereas the contralateral face is represented laterally. Because adjacent parts of the contralateral body project to adjacent areas of the somatic cortex, it is said to be "somatotopically" organized.

13

Caudal to the postcentral gyrus is the posterior parietal cortex. Posterior parietal

cortex is important for forming a mental image of how the outside world is spatially organized and where the body is located within it. You can find the posterior boundary of the parietal lobe by locating the parietooccipital sulcus on the medial surface of the hemisphere (Atlas Figure 2) and connecting a line between it and the caudal end (~80%) of the inferior temporal gyrus. The cortex behind this line and behind the parietooccipital sulcus on its medial surface is the occipital cortex. How does the body map in the postcentral gyrus compare with that in the precentral gyrus? ________________ _______________(11)

The occipital lobe. The most important function of the occipital lobe is the processing of visual information. On the lateral surface of the hemisphere (Atlas Figure 2) find the lateral occipital gyri On the medial surface (Atlas Figure 4) note the prominent and deep calcarine fissure (or sulcus) which runs from rostral to caudal and separates the occipital lobe into an inferior part (the lingual gyrus) and a superior part (the cuneus). This area of cortex is also referred to as the calcarine cortex. In the calcarine cortex of each hemisphere, there is a representation of the contralateral half of the visual world, which like that of the motor and somatosensory cortices has a topographic, or 'visuotopic' organization; the central visual field is represented near the caudal pole of the calcarine cortex and peripheral vision is represented rostrally. What divides the occipital cortex from the parietal cortex on the lateral surface of the cortex? _________________________________(12) On the medial surface? _______________________ ___________________(13)

The temporal lobe. Reexamine the lateral surface of the hemisphere (Atlas Figure 2) and find the lateral sulcus (or Sylvian fissure). Trace it from rostral to caudal. The cortex inferior to the lateral sulcus is the temporal lobe. Find the superior, middle, and inferior temporal gyri. The temporal cortex continues into the lateral sulcus where its dorsal surface contains the transverse temporal gyri of Heschl, which is the primary auditory receiving area. Carefully pry open the lateral sulcus to visualize these gyri. On the lateral surface of the temporal lobe, auditory association areas are represented. In the left hemisphere of most individuals, the posterior part of the superior temporal gyrus and nearby regions of the inferior parietal lobe are involved with comprehending language. This region's function is thus closely related to that of the speech area in the frontal lobe. What is the term used to denote a language deficit? __________________________________(14) What is one important function of association areas of the temporal lobe? ___________________ _______________(15)

On the inferior surface of the temporal lobe (Atlas Figure 3), locate the occipitotemporal gyrus, and the collateral sulcus which separates it from the medially located parahippocampal gyrus and the uncus, the most medial part of the temporal lobe. The uncus and the anterior part of the parahippocampal gyrus are part of the primary olfactory cortex. Identify the olfactory nerves (cranial nerve I) on a gross

14

specimen. The insular lobe. In the depths of the lateral sulcus lies a fifth cortical lobe, called

the insula (meaning island). On a gross specimen the insula can be observed by gently prying open the lateral sulcus and then pushing aside the numerous large blood vessels that run through it. Identify the insula also in a horizontal section such as those of Atlas Figure 13. Although the functions of the insula are largely unknown, it is thought that this area may be involved, among other things, with gustatory and visceral sensations and with monitoring the internal state of the body. What gyri constitute primary auditory cortex? __________________________(16)

The Basal Ganglia Additional important tissue masses derived from the

telencephalon are the basal ganglia. The basal ganglia have an important functional role in the control of movement, and cell groups here are functionally interrelated with motor areas of the frontal lobe. The large aggregations of cell bodies comprising the basal ganglia are located deep within the cerebral hemispheres and underlie the cerebral cortex. Their spatial relationship to the cerebral cortex can be seen in Atlas Figure 13, which shows the large nuclei of the caudate, putamen, and globus pallidus lying immediately subjacent to the insula.

The horizontal sections shown in Atlas Figures 12 and 13 show several

components of the basal ganglia. The caudate nucleus is an arc-shaped structure which, begins rostrally as a large swelling (the head of the caudate) in the lateral wall of the anterior part of the lateral ventricle. As the caudate nucleus arches dorsally and laterally, it becomes thinner and, more laterally, its tail lies in the roof of the temporal horn of the lateral ventricle. Find the head and tail of the caudate on Atlas Figures 12-14. A closely related telencephalic nucleus is the lenticular (i.e., lens shaped) nucleus, which consists of the putamen (i.e., peel or husk) and globus pallidus. All of these components of the basal ganglia are involved with motor control mechanisms. What part of the cerebral cortex is involved with motor control? ________________________(17)

The amygdala, physically near but not part of the basal ganglia, lies deep to the uncus and at the rostral tip of the temporal horn of the lateral ventricle. You can find this large mass of cells in a section such as that shown in Atlas Figure 22. The amygdala is involved in emotional expression. What sensations are represented in the cortex of the uncus, which overlies the medial side of the amygdala? _______________________________________ __________(18)

The Diencephalon. A second major derivative of the prosencephalon is the diencephalon. Its overall shape is best appreciated in a dorsal view of a brain from which the cerebral hemispheres and cerebellum have been removed, as in Atlas Figure 5. During development the diencephalon differentiates into several nuclear groups, the most prominent of which are the thalamus and hypothalamus.

The thalamus consists of paired egg-shaped structures enclosed by the cerebral

15

hemispheres. Locate the thalamus in a hemisected brain (Atlas Figure 4 and 5). Thalamus means "antechamber" and is aptly named because virtually all information passing to the cerebral cortex first synapses or "relays" on cells in this part of the diencephalon. Axons from the thalamus reach the cortex by means of an important, fan-shaped fiber system called the internal capsule, which also contains axons leaving the cerebral cortex. Find the internal capsule in Atlas Figures 12-15, 21-28.

Atlas Figure 13 is a horizontal section through the thalamus. The thalamus consists of a number of nuclear groups; each nucleus has a different function and is linked with particular parts of the cerebral cortex. On a gross specimen locate the optic (II) nerve, the optic chiasm (where optic nerve axons cross), and the optic tract (the part of the fiber tract proximal to the chiasm). Trace the course of these axons centrally into the diencephalon, and try to identify their termination in the Lateral Geniculate Nucleus (LGN; use Atlas Figures 6 and 12 as a guide). Axons of LGN neurons project to the occipital lobe. What fiber system interconnects the thalamus and cerebral cortex? ________________________(19) What fiber system interconnects the left and right cerebral cortical hemispheres? _____________________(20)

As its name implies, the hypothalamus lies inferior to the thalamus. Using Atlas Figure 3 as a guide, identify the hypothalamic region on the brain's ventral surface by locating the tuber cinereum and mammillary bodies. These are prominent eminences associated with hypothalamic nuclear groups. The hypothalamus functions as a regulatory center for many important autonomic functions such as osmotic regulation, feeding, endocrine control, etc. The hypothalamus can also be seen in a hemisected brain (see Atlas Figure 4). On the medial surface of the midsagittally sectioned brain, there is a shallow depression just inferior to the thalamus, which separates it from the hypothalamus below. This groove is the rostral extension of the sulcus limitans and is called the hypothalamic sulcus. The part of the hypothalamus which you can see here is only the medial surface, and the nuclear group extends a few millimeters laterally, beneath the thalamus. Identify the hypothalamus (Atlas Figures 10 and 11) and note its relationship to the nearby 3rd ventricle. What is one major function of the thalamus? _______________________(21)

THE MESENCEPHALON

The mesencephalon, or midbrain, is located immediately caudal to the

diencephalon. The ventral two-thirds of the mesencephalon constitute the cerebral peduncles. 'Peduncle' is derived from the Latin word for foot, and the cerebral peduncles are so named because they appear to support the cerebral hemispheres. The cerebral peduncles (see Atlas Figures 3 and 6) consist of all of the midbrain except for the superior and inferior colliculi (see below). The two major internal structures are the crus cerebri and the substantia nigra. On their ventral surface the cerebral peduncles are separated by a deep groove called the interpeduncular fossa (Atlas Figure 3 and 6). Immediately deep to each of these elevations is the crus cerebri which consists of massive bundles of axons that arise from the cerebral cortex and project

16

caudally to the brainstem and spinal cord. Some of these axons originate in the motor cortex and project through the brain- stem and into the spinal cord. These axons comprise the corticospinal tract (Atlas Figure 23) which is the major descending pathway involved with the control of voluntary movement. Using Atlas Figure 23, trace the course of these axons from the cerebral cortex through the internal capsule, crus cerebri and pons. In what part of the cerebral cortex (lobe/gyrus) does this pathway originate? _________________________(22) Deep to the crus cerebri is the substantia nigra (Atlas Figures 10 and 24).

The mesencephalon contains a dorsal tectum or roof, consisting of the inferior and superior colliculi (hills), both of which are alar plate derivatives. Identify them on a gross brainstem where they can be recognized as two pairs of bumps on the dorsal surface of the midbrain (e.g., Atlas Figure 5). The inferior colliculus processes auditory information and relays it to the medial geniculate nucleus in the thalamus. To what part of the cerebral cortex does the medial geniculate project? ________________________(23) The superior colliculus is involved with reflexive eye movements and receives input from the optic tract. What thalamic nucleus also receives inputs from the optic tract? ________________________________(24)

A third part of the midbrain, situated between the aqueduct and the crus cerebri, is the tegmentum (also meaning roof or covering). It includes the reticular formation, the substantia nigra and the red nucleus. The substantia nigra contains dopaminergic neurons that project to the corpus striatum (caudate and putamen); these neurons degenerate in Parkinson's disease, thus depriving basal ganglia structures of an essential neurotransmitter. Its black color is due to the presence of melanin, a by-product of dopamine synthesis. The regional distribution of these and other monoaminergic neuronal groups are reviewed in Atlas Figures 90-96. The red nucleus receives inputs from motor areas of the cerebral cortex and from the cerebellum. Axons of some of the red nucleus cells descend as the rubrospinal tract; they decussate immediately upon leaving the nucleus (see Atlas Figure 76), and they terminate in the anterior horn of the contralateral spinal gray matter. Find this structure in coronal section in Atlas Figures 25 54 and 65-66. The red nucleus also projects to the inferior olive.

THE RHOMBENCEPHALON

The rhombencephalon differentiates into two brain vesicles, the metencephalon and the myelencephalon. The metencephalon develops into the cerebellum and the pons. The cerebellum has two paired, convoluted hemispheres (the cerebellar cortices) and is important in the coordination of movements. Immediately inferior to it is the pons. Identify the pons and cerebellum on a gross brain specimen. The Pons. Caudal to the mesencephalon is the pons. The bulge which you can see on the ventral surface of the pons (e.g., Atlas Figure 6) is caused by bundles of axons

17

running from medial to lateral. These axons connect neurons of the pontine nuclei, which lie deep to them, with the cerebellar hemispheres. Also located deep within the pons are tracts running from rostral to caudal and vice versa, as well as cranial nerve sensory and motor nuclei. The Cerebellum. The cerebellum is an important motor control and coordinating center. It monitors the accuracy of intended movements by comparing sensory information, for example from the limbs, with motor commands originating in the motor cortex, and then sends corrective signals back to the motor cortex, via the thalamus. If you examine a brainstem specimen where the cerebellum has been removed (e.g., Atlas Figure 5) you can see that it was attached to the brainstem by three large fiber tracts, called the cerebellar peduncles. The superior, middle, and inferior peduncles are bundles of axons, which convey inputs to and/or outputs from the cerebellum. Examine a cerebellum on a gross brain (and Atlas Figure 3) and in coronal sections ( see also Atlas Figures 11 and 29). You will notice that like the cerebral cortex, the cerebellar cortex consists of gyri and sulci, though the gyri are thinner. Unlike the cerebral hemispheres, however, the cerebellar hemispheres are continuous on the midline with a structure called the vermis (Atlas Figure 4). There is a smaller flocculonodular lobe, which is shaped somewhat like a dumbbell, oriented mediolaterally across the bottom of the cerebellum. Part of it can be seen in midsagittal section (nodulus, Atlas Figure 4) and part on the ventral surface of the gross cerebellum (flocculus: Atlas Figure 3). Given that the right cerebellar hemisphere receives sensory information from the right side of the body, what cerebral cortical hemisphere projects motor command information to it? ________________(25)

THE MYELENCEPHALON The myelencephalon develops into the medulla oblongota, or simply the medulla, which is physically continuous rostrally with the pons and caudally with the spinal cord. A small, but functionally important part of the neuraxis, the medulla is an important brainstem center for the control of autonomic functions such as respiration and blood pressure. Not only does the medulla contain cranial nerve nuclei whose functions are in many cases life sustaining, but it also contains numerous fiber pathways connecting the upper (i.e., telencephalic) and lower (i.e., spinal) regions of the brain. Thus, localized damage, caused for example by a vascular problem such as a blockage or a hemorrhage, can have widespread and life-threatening consequences.

The medulla's gross structure can be seen on Atlas Figure 6 from the ventral surface. On a gross specimen locate the two prominent bulges on the lateral surface, called the 'olives', and then identify the underlying inferior olivary nuclei on a section such as that in Atlas Figure 43. The inferior olivary nuclei are important motor nuclei for relaying information to the cerebellum. Just medial to the olives are the medullary pyramids. These are bundles of motor control axons in the corticospinal tract.

18

Corticospinal tract axons originate from neurons in the precentral gyrus of the frontal lobe and project to the contralateral spinal cord. The crossing or 'decussation' or these axons can be seen at the most caudal end of the medulla, called the spinomedullary junction. Where are the corticospinal axons located in the mesencephalon? _______________ _______________(26) In the pons? _______________________(27)

THE SPINAL CORD The spinal cord is composed of 31 segments corresponding to the 31 pairs of

sensory and motor nerves whose peripheral processes innervate the sensory receptors and muscles of the body (see Atlas Figure 31). The organization of the adult spinal cord most closely resembles that of the embryonic neural tube, having a dorsal sensory region and a ventral motor region. In addition to cells involved with processing incoming sensory and outgoing motor information, the spinal cord contains axons of long ascending and descending tracts. The names of these tracts signify their origin and termination; thus the spinothalamic tract has its cells of origin in the spinal cord and the axons of these cells synapse on cells in the thalamus. The spinal cord thus provides a critical link between the brain and body regions below the head.

19

Cranial Nerves Peripheral sensory and motor structures of the head are innervated by cells in the brain proper that are analogous to dorsal root ganglion neurons and spinal motoneurons. There are 12 cranial nerves. You should be able to identify each of the cranial nerves and their actions (from the Table below). Except for nerves I (olfactory) and II (optic), the cranial nerves attach to the brain in the brainstem.

TABLE OF CRANIAL NERVES AND ASSOCIATED STRUCTURES

Cranial nerve Functional Component

Peripheral Termination Action

III oculomotor

General somatic efferent General visceral efferent

Eye muscles Ciliary ganglion

Move globe Raise eyelid; lens accommodation

IV trochlear

General somatic efferent Eye muscle Move globe

V trigeminal

Special visceral efferent General somatic afferent

Jaw muscles Skin on tongue/face; cornea

Mastication Somatosensation

VI abducens

General somatic efferent Eye muscle Move globe

VII facial

Special visceral efferent General visceral efferent Special visceral afferent General somatic afferent

Mimetic musculature Stapedius muscle of inner ear Nasal/salivary glands; Taste buds (anterior 2/3 of tongue) Skin behind ear

Facial expression Sound dampening Salivation Taste Somatosensation

VIII Vestibulocochlear

Special somatic afferent Cochlea Balance, hearing

IX glossopharyngeal

Special visceral efferent General visceral efferent General somatic afferent Special visceral afferent

Pharyngeal muscle Parotid salivary glands Ext. acoustic meatus (ear) Taste buds (post 1/3 tongue)

Swallowing Salivation Somatosensation Taste

X vagus

Special visceral efferent General visceral efferent General somatic afferent Special visceral afferent General visceral afferent

Pharynx, larynx, esoph., palate G.I. tract/heart/lungs Ear Epiglotis Pharyx, larynx, trachea., gut

Swallowing Parasymp. Efferent Somatosensation Taste Parasymp. Afferent

XI Spinal accessory

General somatic efferent Neck muscles Move head on neck

XII hypoglossal

General somatic efferent Intrinsic muscles of tongue Tongue movement

20

REVIEW QUESTIONS LAB 1 (28) a) Where are the cell bodies of origin of a thalamocortical pathway? b) To what structure do the axons project? For Questions 29 - 36 match the structures with the following:

a) Telencephalon

b) Diencephalon

c) Mesencephalon

d) Myelencephalon

e) Metencephalon (29) Crus cerebri (30) Corpus callosum (31) Head of caudate nucleus (32) Hypothalamus (33) Vermis (34) Decussation of corticospinal tract axons (35) Internal Capsule (36) Calcarine fissure

21

For Questions 37 to 46 match the given term with the following cortical lobe(s). a) frontal, b) parietal, c) occipital, d) temporal, e) Insula (37) Aphasia. (38) Visual representation. (39) Leg medial, face lateral. (40) Olfaction. (41) Broca's area. (42) Gustation. (43) Somatosensation. (44) Audition. (45) Postcentral gyrus. (46) Voluntary movement.

22

ANSWERS TO REVIEW QUESTIONS LABORATORY EXERCISE 1 1. Basal plate 2. Sulcus limitans 3. Frontal lobe 4. Occipital 5. Corpus callosum 6. Right 7. Adjacent parts of the motor cortex control adjacent muscle groups on the body 8. Medially 9. Broca's area: caudal aspect of inferior frontal gyrus 10. Most of frontal lobe except for motor control areas 11. It is the same, with the leg medial, arm and face lateral 12. A line drawn between the top of the parieto-occipital sulcus and the caudal end of

the inferior temporal gyrus 13. Parieto-occipital sulcus 14. Aphasia 15. Language comprehension 16. Transverse gyrii of Heschl 17. Frontal lobe 18. Olfactory 19. Internal capsule 20. Corpus callosum

23

21. Process and relay information to the cerebral cortex 22. Frontal lobe; precentral gyrus 23. Temporal lobe 24. Lateral geniculate nucleus 25. Left 26. Crus cerebri 27. Basilar part of pons 28. a) thalamus b) cerebral cortex 29. Mesencephalon 30. Telencephalon 31. Telencephalon 32. Diencephalon 33. Metencephalon 34. Myelencephalon 35. Telencephalon 36. Telencephalon 37. Frontal or temporal 38. Occipital 39. Frontal, parietal 40. Temporal 41. Frontal 42. Insular

24

43. Parietal 44. Temporal 45. Parietal 46. Frontal

25

LABORATORY EXERCISE 2 MENINGEAL COVERINGS, VENTRICLES AND BLOOD VESSELS

OF THE CENTRAL NERVOUS SYSTEM

INTRODUCTION The meningeal coverings of the brain and the cerebrospinal fluid/ventricular system together provide mechanical support and stabilization of the brain within the cranial cavity and spinal column. Blood supply to the brain is regionally organized. Vascular-related problems are a common cause of neurological disorders and an understanding of regional blood supply and functional neuroanatomy is critically important clinically and also for interpreting brain imaging studies of brain function. At the end of this exercise, you should be able to: 1) describe the relationship between the meninges and components of the

blood supply including arteries, veins and venous sinuses. 2) identify all of the ventricles and trace the flow of cerebrospinal fluid through

the brain. 3) describe the overall organization of the internal carotid and basilar arterial

systems 4) using information from Laboratory Exercise 1, match the function of a given

brain region with its arterial supply.

THE VENTRICULO-MENINGEAL SYSTEM

The Meninges

Within the cranium and spinal column the living brain is suspended in a clear liquid called cerebrospinal fluid and is invested with three layers of non-neural connective tissue membranes. These membranes are called meninges and consist of the dura mater, arachnoid and pia mater, the latter two often being referred to collectively as the leptomeninges. Each of these membranes forms a separate, continuous sheet around the brain and spinal cord. The Netter book (available in the laboratory) has good illustrations of the meninges and blood vessels. Also, be sure to look at the museum specimens in the cases. Dura mater. As its name implies, the dura mater, or dura, is a tough, skin-like membrane that covers the brain and spinal cord. If available, examine a gross brain having most of its dural covering intact. Especially prominent is the falx cerebri, a long sickle-shaped extension of dura which divides the cranium into paired lateral compartments containing the cerebral hemispheres.

26

Examine a laboratory specimen of the dura mater. Along the dorsal midline of the dura it is possible to see aggregations of whitish, tuft-like structures called the arachnoid villi or arachnoid granulations. The villi, which often become heavily calcified in older adults, serve as one-way valves in passing cerebrospinal fluid into the venous system. The large spaces occupying the dura mater along the midline are dural sinuses, which accommodate the venous drainage of the brain; these will be discussed below. Pia-arachnoid. Inferior to the dura and separated from it by the subdural space is a more delicate membrane called the arachnoid. Like the dura mater, the arachnoid envelops the brain, passing over the sulci in the cerebral hemispheres, rather than following the contours of its surface. The arachnoid is closely applied to the dura, although a potential space separates the two meningeal layers. In contrast to the dura and arachnoid, the pia mater adheres intimately to the nervous tissue that underlies it and thus follows the contours of the brain closely. Would you find arachnoid or pia, or both, in the depths of the central sulcus? ____________________(1) Arachnoid trabeculae, which resemble a lattice-work of connective tissue, extend from the arachnoid to the pia. Blood vessels traverse this subarachnoid space, which contains the cerebrospinal fluid (CSF). Note that during fixation and removal of the brain from the cranium the CSF is lost and the meninges shrink, obliterating the subarachnoid space in many locations. The Ventricles The brain and spinal cord contain approximately 150 cc of cerebral spinal fluid (CSF). CSF is produced in four distinct cavities called ventricles. These cavities originate from the lumen of the embryonic neural tube. Examine a metal casting of the ventricles provided in the laboratory. A metal casting of the four ventricles and their relation to the skull may be found in museum case 16-22. There are two lateral ventricles, one in each of the paired cerebral hemispheres. Each is an arc-shaped cavity starting from the rostral end of the hemisphere and turning ventrally and then rostrally again to terminate at the tip of the temporal lobe. At the junction between the body of the ventricle and the temporal horn, is the occipital horn, a posterior extension of the ventricle. The third ventricle is a thin, elongated cavity lying in the midsagittal plane of the diencephalon; its lateral walls are formed by the medial aspects of the thalamus and hypothalamus, and its rostral wall is formed by the lamina terminalis (see Atlas Figures 4, 5 and 14). What is the lamina terminalis in the embryonic neural tube? ___________________________(2) In the brainstem, the fourth ventricle is shaped like a pyramid, with its apex extending up into the cerebellum and its base coincident with the upper surface of the pons and medulla. The lateral ventricles are connected to the third ventricle by the paired interventricular foramina (foramina of Monro) which you should locate near the rostral-most part of the diencephalon in a midsagittally sectioned brain and in Atlas Figure 4; its location can also be discerned in the horizontal section of Atlas Figure 14. The third ventricle is

27

connected to the fourth via the cerebral aqueduct (or aqueduct of Sylvius) which is a midline, tube-like structure a few centimeters in length and about as thick as a pencil lead e.g., Atlas Figures 11 and 54. Identify a lateral ventricle, an interventricular foramen of Monro, the third and fourth ventricles and the cerebral aqueduct in your gross brain specimen. Be sure to examine Atlas Figures 9-17 and identify the cerebral ventricles and the major structures that form their walls. Also, you should be able to identify major components of the ventricular system on CT and MRI images in Atlas Figure 8. What structure forms the lateral wall of the lateral ventricle? ____________________(3) The lateral wall of the third ventricle? _____________________________(4) CSF formation and circulation. Cerebral spinal fluid (CSF) consists of water (~99% of its content) proteins, glucose and ions such as sodium potassium, calcium, magnesium, and chloride). The brain contains ~130 ml of CSF, the remaining ~20 ml being in the spinal cord. Only ~25 ml are actually contained within the ventricles, though the size of ventricles varies greatly from individual to individual; the rest is in the subarachnoid space. The entire volume is replenished 3-4 times per day. CSF provides mechanical support of the brain which partially floats within the cranium and spinal cord. CSF is also important for regulating the composition of fluids that bath CNS neurons and glia. Its flow through the ventriculo-meningeal system provides a route through which chemical signals can be distributed throughout the CNS and metabolites can be removed. CSF is formed by modified capillaries called choroid plexus. These structures are located in the lateral, third, and fourth ventricles. After formation in the ventricular system, CSF passes out of the brain through three openings in the brainstem, the two lateral openings (the foramina of Luschka) and the medial opening (the foramen of Magendie); memory aid; lateral-Luschka, medial-Magendie. Identify these in a gross specimen; the foramina of Luschka can often be located by noting choroid plexus protruding from the lateral sides of the cerebellum. CSF circulates up and around the brain in the subarachnoid space, and is passively absorbed into the venous system via the arachnoid villi. The CSF of the ventricles communicates with the subarachnoid space only through foramina in the fourth ventricle. Some CSF flows into the subarachnoid space of the spinal cord and eventually into the lumbar cistern. It is unclear how much direct access CSF has to neurons and glia, though some exchange likely occurs near capillaries.

ARTERIAL VESSELS Two major arterial systems provide blood to the brain. The internal carotid system provides blood to most of the forebrain, including the cerebral hemispheres, basal ganglia, thalamus and hypothalamus. The vertebral-basilar system provides blood to the medulla, pons, midbrain and cerebellum and to posterior regions of the diencephalon and cerebral cortex. Small vessels, called communicating arteries, provide for interconnections between the two arterial systems, forming a structure called

28

the Circle of Willis. Internal Carotid System The internal carotid artery (there is one of each side) arises from the common carotid artery, courses upward through the neck, pierces the base of the skull and passes through the dura at the base of the brain. There it gives rise to two major branches, the anterior and middle cerebral arteries (Atlas Figures 99, 100, 101, 103-105). The middle cerebral artery (MCA) is a direct continuation of the internal carotid. It runs laterally and superiorly through the lateral fissure. As it ascends it gives off numerous small branches called lenticulo-striate arteries that supply most of the lateral aspect of the caudate and putamen and the genu and posterior limb of the internal capsule (Atlas Figure 103). Blockage of these latter vessels, in particular, can lead to severe sensorimotor dysfunction. The MCA distributes branches widely to the insular, frontal, parietal, temporal and occipital lobes on the lateral surface of the cerebral cortex. The MCA is readily visible on many of the gross specimens. Branches supply specific regions, which they are named for, e.g., central sulcus branch. The branching pattern varies extensively; you do not need to be able to identify specific branches, just the general territory of the MCA. The angiograms in Atlas Figures 107 and 108 provide excellent views of the MCA. The anterior cerebral artery (ACA) branches off of the internal carotid and runs anteriorly, superiorly and medially to supply medial parts of the basal ganglia and thalamus and medial aspects of the cortex, e.g., the cingulate gyrus, caudally to approximately the level of the parieto-occipital sulcus. The ACA forms a distinctive curve or “nose” as it arches up and around the rostral part of the corpus callosum (Atlas Figure 101) and can usually be seen readily in a hemisected brain. . There is an arterial border zone, called leptomeningeal anastomoses, between the territory of the middle and anterior cerebral artery located medially on the lateral surface of the cerebral hemisphere. Blood supply to these cortical areas can arise from either the ACA or MCA or both. Vertebral-Basilar System The paired vertebral arteries course over the anterior surface of the medulla (Atlas Figures 99, 111 and 112). They give rise to 1. the posterior spinal artery, 2. the anterior spinal artery, and 3. an artery that supplies the posterior part of the cerebellum (the posterior inferior cerebellar artery – you are not responsible for the name). Near the pontomedullary junction the vertebral arteries merge to form the unpaired basilar artery, a large midline trunk on the anterior surface of the brainstem. Circumferential branches of the basilar artery supply the interior of the medullar, pons and midbrain, as well as

29

most of the cerebellum. The basilar artery ends just caudal to the mammillary bodies where it branches to give rise to the posterior cerebral arteries (PCA). Occasionally the posterior cerebral artery(ies) arise from the internal carotid. The PCAs supply posterior regions of the diencephalon. An important branch, the calcarine artery, supplies areas near the calcarine sulcus, which contain primary visual cortex (Atlas Figure 101). The PCA can be seen clearly in the angiogram of Atlas Figure 112. The spinal cord is supplied by the anterior spinal artery which is a single, unpaired vessel having penetrating branches to the anterior third of the spinal cord. The anterior spinal artery originates as two branches of the vertebral arteries which join at the midline near the spinomedullary junction (Atlas Figure 99). The posterior spinal arteries course diffusely over the posterior surface; these supply the posterior two-thirds of the cord. The Circle of Willis The internal carotid and vertebral/basilar systems are joined by an anastomotic ring at the base of the brain called the Circle of Willis (Atlas Figure 99). This ring is formed anteriorly by the anterior communicating artery and the left and right anterior cerebral arteries. The right and left posterior communicating arteries connect their respective internal carotid arteries with posterior cerebral arteries. Inspect the base of a gross brain specimen and identify components of the Circle of Willis. The posterior communicating arteries are often of unequal size. From what major vessel do the MCA and PCA arise –the MCA?____________________(5) the PCA? __________________ (6) Identify the anterior communicating artery; it may be large or small, even hair-like. Variations in pattern of the circle of Willis occur in roughly 50% of people. Compare the arteries on your specimen with others.. The Circle of Willis constitutes the major, but not exclusive, component of the intracranial collateral circulation. What is another site of collateral or shared circulation in the brain? _____________________________________(7)

THE MAJOR VEINS Unlike many veins of the body, cerebral veins do not generally travel in close proximity to arteries. Instead they emerge from the substance of the brain. Venous patterns are quite variable, and unlike the arterial system there are numerous anastomoses among them. Cerebral veins are divided into two main groups. Superficial veins lie on the surface of the hemisphere and most of them empty into the superior sagittal sinus (Atlas Figure 106). Deep veins drain internal structures, e.g., thalamus, and eventually empty into the

30

straight sinus (Atlas Figure 102). The straight sinus courses posteriorly (above the cerebellum) to join the superior sagittal sinus at the confluence of the sinuses. From there blood flows via the transverse sinuses eventually into the internal jugular vein. Other, small veins drain deep areas of the brain, e.g., hypothalamus, and flow into the large cavernous sinus at the base of the skull, which in turn eventually empties into the internal jugular.. Most veins of the brainstem, including the cerebellum, eventually drain into the internal jugular, whereas those of the caudal medulla drain into the anterior and posterior spinal veins. These in turn connect with veins of the thoracic, abdominal and pelvic cavities. Which veins drain into the superior sagittal sinus? ____________________________________(8)

REVIEW QUESTIONS (9) Make the best match:

a) Foramen of Monro I. If occluded, may prevent circulation of CSF from third to fourth ventricle

b) Cerebral Aqueduct II. One of its walls contains the

hypothalamic sulcus

c) Arachnoid villi III. Normally permits CSF formed in the lateral ventricle to flow into third ventricle

d) Third Ventricle IV. Major site of transfer of CSF from

subarachnoid space to venous system

(10) Between which meningeal layers do surface blood vessels travel? (11) What major artery supplies the cingulate gyrus? (12) Cortically-mediated deficits in visual perception would most likely be associated with occlusion of which specific artery? From what major vessel does this artery emerge?

(13) What arteries comprise the Circle of Willis?

31

ANSWERS TO REVIEW QUESTIONS LABORATORY EXERCISE 2

1. Pia 2. It’s most rostral end. 3. Caudate 4. Thalamus 5. Internal carotid 6. Basilar (via vertebral arteries) 7. Leptomeningeal anastomoses or borders between MCA and ACA 8. Superficial cerebral veins 9. a) III; b) I; c) IV; d) II 10. Arachnoid and pia mater 11. Anterior cerebral artery 12. Calcarine artery, branch of posterior cerebral artery 13. anterior communicating artery, anterior cerebral arteries, posterior communicating arteries, posterior cerebral arteries

32

LABORATORY EXERCISE 3

Gross Anatomy and Internal Structures of the Spinal Cord INTRODUCTION

The spinal cord constitutes a vital link between the brain and most of the body.

Within it are long tracts of ascending and descending axons that transmit sensory and motor information up and down the neuraxis. Cell groups within the spinal cord are typically long, continuous columns of cells which are involved with processing the incoming sensory and outgoing motor information. Although certain reflexes can be mediated by some of these mechanisms contained within the spinal cord itself, damage to the spinal cord can disrupt the flow of information necessary for conscious appreciation of sensory events and voluntary control of limb, trunk and bladder movements.

In today's laboratory you will study in detail the gross anatomy and intrinsic organization of the spinal cord. At the end of today's exercise you should be able to:

1) describe the external topography of the spinal cord and its meninges 2) identify the posterior columns, corticospinal and spinothalamic tracts and

their functions 3) identify the principal cell groupings and their functions 4) understand some of the basic principles underlying the organization of the

spinal cord GROSS ANATOMY

Though the spinal cord is a continuous unsegmented structure it is considered to consist of 31 segments defined by their corresponding pair of dorsal and ventral roots (8 cervical, 12 thoracic, 5 lumbar, 5 sacral, 1 coccygeal). The peripheral processes of the dorsal root ganglion cells and of fibers of the ventral root join to form a spinal nerve which leaves the vertebral canal by an intervertebral foramen. The cutaneous area supplied by a single dorsal root and its ganglion is called a dermatome; the somatic musculature supplied by a ventral root is called a myotome. As a frame of reference: C3 = middle finger, T4 = nipple, T10= umbilicus, L5=big toe (see diagram on next page).

The spinal cord extends from the base of the skull to the lower border of the first lumbar vertebra where it terminates as a conical-shaped structure called the conus medullaris. This structure is located at the L2 vertebral level; below vertebral level L2 the vertebral column contains only dorsal and ventral roots of the spinal nerves which will exit the column at lower levels (see Atlas Figure 31). This bundle of nerve roots is called the cauda equina. Identify the cauda equina on a gross specimen. Be sure to look at the two excellent dissections of the vertebral column in the museum case.

The spinal cord is enlarged at two locations, which you should identify on a gross specimen (see Atlas Figure 31). The cervical enlargement is centered on lower cervical

33

spinal segments; these segments have spinal roots that innervate the hand. A smaller lumbosacral enlargement is centered on lower lumbar and upper sacral spinal segments, corresponding to those segments that innervate the foot. The enlargements are due to the large number of motoneurons and spinal interneurons at these levels that control the muscles of the distal extremities and that process sensory information from skin and muscles there. In cross section, e.g., Atlas Figure 36, the spinal cord is seen to consist of an H-shaped central core of gray matter surrounded by a "rind" of white matter (N.B. the terms gray and white refer to the appearance of fresh specimens, not necessarily to stained sections).

The spinal cord is protected within the vertebral column by the hydrodynamics of the cerebrospinal fluid and the spinal meninges. These membranes are continuous with the cerebral meninges and the spinal subdural and subarachnoid spaces are thus continuous with the corresponding cranial spaces. Cerebrospinal fluid (CSF) is produced by the ____________________________________________________(1) located in the ________________________________ ____________(2) ventricles.

34

INTERNAL STRUCTURES OF THE SPINAL CORD

The following parts of this exercise will require you to learn some of the detailed anatomy of the spinal cord. While reading the material and answering the questions in the text locate the relevant structures in Atlas Figures 32-38. You should begin with a representative cross section such as Atlas Figure 36, which is a transverse section at a thoracic level. Figure A at the end of this exercise has outlines of spinal cord cross sections at cervical and lower thoracic levels that you can use as a study aid by drawing in fiber tracts and nuclei (see Exercise at the end of the chapter).. Gray Matter

The spinal cord gray matter contains many neuronal somata, dendrites and finely myelinated and non-myelinated axonal processes as well as glia. The sides of the "H" are called the posterior (dorsal) gray columns and the anterior (ventral) gray columns. These columns are frequently referred to as "horns", e.g., posterior horn.

Cell columns of the two sides are joined across the midline by gray matter anterior and posterior to the central canal. A nuclear column, or group of neurons, all of which may have similar function, is referred to as a nucleus. Some of the nuclear columns extend without interruption throughout the length of the spinal cord. Other columns are discontinuous. Atlas Figures 34-38 are stained for myelin; thus the fiber tracts are dark and the grey matter is light. Entry of afferent fibers into the spinal cord. The dorsal roots and the cells of the posterior horn are associated with afferent (sensory) pathways. All central processes of the cells in the dorsal root ganglion enter the spinal cord in the dorsal root. Each dorsal root ganglion cell has a single, long axon that extends peripherally and centrally; unlike most neurons, it lacks typical dendrites. Action potentials generated near the sensory endings in the skin, muscle or viscera are propagated actively down the entire length of this long axon, past its cell body in the dorsal root ganglion. The peripheral processes of dorsal root ganglion cells innervate sensory receptors in the skin, joints, periosteum, muscles, fascia and viscera. The central process of a dorsal root ganglion cell divides into an ascending and a descending branch. Each of these branches may give off several collaterals that synapse upon neurons in the spinal gray matter in or near the segment of entry; others ascend or descend to more distant regions. Posterior horn. There are no synapses within a dorsal root ganglion. Therefore, synaptic circuitry in the posterior horn constitutes an initial, and critical, juncture for the distribution, modulation and transmission of somatic information to other regions of the brain. The cellular anatomy and physiology of this part of the spinal cord are quite complex. A simplified view is that the posterior horn contains two types of neurons: a) neurons with long-distance projecting axons (for example, to the thalamus) and b) local inter-neurons whose axons synapse on nearby cells, located in the same or neighboring spinal segments. A particularly important nucleus is the substantia gelatinosa, which contains local inhibitory neurons. It can be identified in the Nissl-stained sections of

35

Atlas Figures 32 and 33, and its location can be discerned in the fiber stained sections, Atlas Figures 34-38. Cells of the substantia gelatinosa play an important role in modifying pain information entering the spinal cord from the dorsal roots.

A distinguishing feature of the gray matter of the thoracic spinal cord is the presence of the dorsal nucleus of Clarke (or the nucleus dorsalis) located at the base of the posterior horn. This readily identifiable cell group receives sensory input from the lower limb, providing information about the limb's position in space (i.e., proprioceptive information). Identify this nucleus on Atlas Figure 33 Axons of these cells pass uncrossed into the white matter, in which they ascend to the ipsilateral cerebellum as the posterior spinocerebellar tract (see below). Note that the dorsal nucleus of Clarke is found only in segments T1 through L2 and is most prominent in lower thoracic and upper lumbar segments. Therefore, afferent fibers innervating the leg must ascend in the spinal cord to reach Clarke's nucleus. An homologous nucleus for the arm is located in the medulla and will be identified later in the course. Intermediate gray. The intermediate gray is located in the area between the base of the posterior horn and the anterior horn. A small but prominent lateral horn (a.k.a., intermediolateral cell column) is present at thoracic and upper lumbar levels (T1 through L2/L3) and is a distinguishing feature of these segments (see Atlas Figure 36). The lateral horn contains preganglionic sympathetic efferent cells. Axons of these cells exit the spinal cord via the ventral roots of spinal nerves T1 through L3 and go to a “chain” of ganglia lying lateral to the vertebral column that contain sympathetic (“flight or fight”) neurons; axon of these sympathetic neurons travel more peripherally to reach their targets, e.g., in skin, muscle. Sacral autonomic nuclei (containing preganglionic parasympathetic neurons) occupy a corresponding position in the lateral part of the intermediate gray of segments S2, S3, and S4 but no lateral horn is present there. Parasympathetic ganglia (and neurons) are located close to their peripheral targets, e.g., in bladder, colon. The cell column in the posterior horn that plays an important role in modifying incoming somatic sensory information is ____________________________(3). Anterior horn. The anterior horns contain groupings of large motorneurons whose axons innervate somatic musculature. Examine Atlas Figure 32 and not that the large motorneurons tend to be clustered together in somewhat ill-defined groups. All the neurons supplying a particular muscle or muscle group tend to be located in the same motoneuron group or "pool". Medial groups innervate the trunk (proximal) musculature principally; laterally located cell groups innervate limb (distal) musculature principally. The laterally located cell columns are more numerous and more populous in the cervical and lumbro-sacral enlargements. Why? _______________________ (4) White Matter

The white matter of the spinal cord contains fiber tracts, or fasciculi, composed of myelinated and non-myelinated fibers. The presence of many myelinated fibers

36

gives the outer "rind" of the spinal cord its whitish appearance in fresh tissue. Examine Atlas Figures 34 and 38; note the difference between sacral and cervical segments in terms of the absolute and relative (to gray matter) amounts of white matter. Why do progressively higher spinal cord segment contain more white matter? __________________________________________________________(5)

For each half of the spinal cord there is a posterior, a lateral and an anterior funiculus. The posterior funiculus lies between the posterior median fissure and the dorsal root entry zone at the posterolateral sulcus. The lateral funiculus lies between the dorsal root entry zone and the site of emergence of the ventral root fibers at the anterolateral sulcus. The anterior funiculus lies between the emergence of the ventral roots and the anterior median fissure. These funiculi contain fiber tracts. Long descending pathways arise in the cerebral cortex or brainstem centers and terminate in the spinal cord gray matter. Long ascending tracts consist of the axons of dorsal root ganglion cells or arise from neurons in the spinal gray and terminate in the brainstem, cerebellum or thalamus. The name of a tract often signifies both its origin and termination. For example the spinothalamic tract originates in the spinal cord and terminates in the thalamus. Where would a corticospinal tract begin and end? _______________________________________________(6) Is it an ascending or a descending tract? ______________________________(7) When studying spinal pathways remember that the structures may not be as discrete and clearly identifiable as the highly diagrammatic figures in textbooks might suggest. Rather they may overlap one another to a considerable degree. Posterior funiculus. The posterior funiculus contains the posterior (or dorsal) columns. These fibers are large diameter, thickly myelinated central axons of dorsal root ganglion cells. The posterior columns carry information essential for making fine tactile discriminations (e.g., distinguishing a dime from a nickel with the fingertips) and for sensing the position of the limbs in space. Where are the cell bodies of origin of posterior column axons? _________________________ _______________(8) At mid-thoracic (T6) levels and higher, the fibers entering the posterior funiculus from the arm cause the white matter to divide into a medial segment (gracile fasciculus) representing the leg and a more lateral segment (cuneate fasciculus) representing the arm (Atlas Figure 37); the dividing line is called the dorsal or posterior intermediate sulcus and can often be observed on gross specimens. Memory aid: “feet walk on grass”. Lateral funiculus. The lateral funiculus contains several ascending and descending pathways. Because of its role in voluntary movement, an exceptionally important descending fiber system is the lateral corticospinal tract. It arises from the motor areas of the cerebral cortex located in the __________________________________(9) lobe on the opposite side of the brain and terminates on motorneurons (and on interneurons) in the anterior horns. Which motoneuron pools in the anterior horns innervate muscles of the distal extremities? ______________________ _______________________(10) What might you expect to happen to the size of the corticospinal tract in progressively lower spinal cord segments? ___________________________

37

__________________(11)

The lateral funiculus contains two ascending pathways. The posterior spinocerebellar tract has already been noted as an ipsilateral pathway arising from Clarke's nucleus; it projects to the cerebellum. In what spinal cord segments is this nucleus located? _______________________________(12) This pathway conveys information to the cerebellum about muscle stretch, as well as touch, pressure and joint position information for the leg. A second ascending pathway, located in the anterolateral aspect of the white matter, is the spinothalamic tract, which is important for conveying information about pain and temperature to higher brain centers. The spinothalamic tract arises from cells in the posterior horn whose axons cross in the ventral/anterior white commissure (e.g., Atlas Figure 35) and ascend to the contralateral thalamus in the diencephalon.

Thus the two major ascending systems carrying somatic sensory

information from a given side of the body ascend on opposite sides of the spinal cord. The posterior columns run (ipsilaterally, contralaterally) (13) and carry information about _________________________________________________(14). The spinothalamic tract runs (ipsilaterally, contralaterally) (15) and carries information about ____________________ _________________________________(16). Do central processes of dorsal root ganglion cells cross to the contralateral side of the spinal cord to form the spinothalamic tract? ________________(17) Anterior funiculus. The anterior white matter contains a number of ascending and descending pathways. These include the anterior corticospinal, vestibulospinal, tectospinal, spino-olivary and spino-tectal tracts. These will be discussed later in the course. Don't worry about their exact locations now; just know that they are located in the anterior funiculus. Intraspinal pathways. In addition to these long ascending and descending tracts the spinal cord contains short ascending and descending fiber systems that begin and end within the spinal cord, interconnecting different levels. Intersegmental spinal reflexes are mediated by these fiber systems. These fibers surround the gray matter on all sides. Some of these tracts are involved also in the local transfer of pain information among spinal cord segments.

38

COMPARISON OF DIFFERENT SPINAL CORD SEGMENTS

As an exercise try to identify different spinal cord segments. In distinguishing spinal cord levels note: 1) the overall size and shape of the sections; 2) the relative and absolute amounts of white and gray matter; 3) the presence or absence of certain cell columns (e.g., those in lateral horn) or fiber tracts (i.e., cuneate fasciculus). Draw in and label the following on the outlines below (outlines are not to scale).

dorsal root ganglion preganglionic sympathetic neurons dorsal and ventral roots dorsal nucleus of Clarke posterior, lateral and anterior funiculi lateral corticospinal tract substantia gelatinosa lateral spinothalamic tract posterior spinocerebellar tract medial and lateral motor columns posterior intermediate sulcus gracile and cuneate fasciculi

C-7

T-12

39

REVIEW QUESTIONS LAB 3 (18) The crossed corticospinal tract is located in the:

a. lateral funiculus b. posterior funiculus c. anterior funiculus

(19) Cells located in Clarke's column project their axons to the (contralateral,

ipsilateral) _______________via the (posterior, anterior) ___________________ tract.

(20) Two distinguishing features of the thoracic spinal cord are:

a. dorsal nucleus of Clarke b. anterolateral sulcus c. lateral horn d. posterior spinal artery

(21) An upper thoracic segment can be distinguished from a lower thoracic segment

by the presence of the _____________________. Questions 22-25: A hemisection of one side of the spinal cord has resulted in the following functional changes.

Match the functional deficits on the left with the relevant tract on the right. (22) loss of pain and temperature on a. lateral corticospinal

right side of the body b. posterior columns (23) loss of light touch and vibration c. lateral spinothalamic

sense on left side of body (24) absence of voluntary movements

on the left side (25) On which side of the spinal cord is the hemisection? (26) The gracile fasciculus contains axons whose peripheral processes innervate

somatic sensory receptors in the:

a. ipsilateral arm b. ipsilateral upper trunk c. contralateral leg d. ipsilateral leg

(27) The cuneate fasciculus is present at what levels?

40

ANSWERS TO REVIEW QUESTIONS

LABORATORY EXERCISE 3

Gross Anatomy and Internal Structures of the Spinal Cord 1. Choroid plexus 2. Lateral, third and fourth 3. Substantia gelatinosa 4. These segments innervate the extremities. 5. Ascending fiber systems accumulate axons;

descending systems have not yet terminated 6. Begin, cortex: end, spinal cord 7. Descending 8. Dorsal root ganglia. 9. Precentral gyrus, frontal lobe. 10. Lateral motoneuron pools. 11. It gets smaller. 12. T1 through L1/L2 13. Ipsilaterally 14. Discriminative touch, proprioception 15. Contralaterally 16. Pain and temperature 17. No! They first synapse in the gray matter on the same side as their

peripheral innervation. It is the postsynaptic cells of the spinal gray matter that contribute axons to the spinothalamic tract.

18. Lateral funciculus.

41

19. Ipsilateral cerebellum, posterior spinocerebellar tract. 20. a and c. 21. Posterior intermediate sulcus (also by presence of the cuneate fasciculus). 22. c 23. b 24. a 25. Left 26. d 27. T6 and above

42

LABORATORY EXERCISE 4

Brainstem

The brainstem at all levels is made up of four basic components. First, it contains rostral parts of the ascending and descending tracts introduced in the spinal cord exercise (for example, the spinothalamic and corticospinal tracts). Second, the brainstem contains all but two of the cranial nerves and their nuclei. Third, the brainstem contains a "core" made up of a variety of nuclei, collectively known as the reticular formation, that has a diversity of functions, including the regulation of sleep and wakefulness. Fourth, the brainstem contains nuclei and fiber tracts associated with inputs and outputs of the cerebellum. By the end of this laboratory you should be able to:

1. identify major ascending and descending axonal pathways that traverse the brainstem. 2. determine which pathways link brainstem nuclei with higher or lower parts of the neuraxis and which pathways are mainly passing through the brainstem to other structures. 3. identify major nuclear groups that, via the brainstem, communicate with the forebrain, cerebellum and spinal cord. 4. identify the sensory and/or motor components of cranial nerves III through XII, and recall which brainstem nucleus or nuclei is/are associated with each nerve. 5. recall the general spatial relationship of brainstem pathways and nuclear groups to one another.

General Organization of the Brainstem

In the spinal cord laboratory, you learned that the adult spinal cord gray matter is

organized with motor structures located ventral to sensory ones and separated from them by the embryonic sulcus limitans. The brainstem is organized in a similar fashion, with motor nuclei separated from sensory nuclei by a more distinct sulcus limitans. The caudal part of the medulla has a gross topography that is quite similar to the spinal cord (see, for example, Atlas Figures 40 and 41), except that the lumen of the neural tube is located more dorsally. Further rostrally, at the level of the obex, the medulla 'opens' to form the IVth ventricle (Atlas Figure 44). This opening causes the dorsal nuclei of the grey matter nuclei to move laterally, so that alar plate derivatives (sensory nuclei) become situated dorsolaterally and basal plate derivatives (motor nuclei) are situated ventromedially to them.

Examine a gross brainstem from which the cerebellum has been removed, and identify the sulcus limitans; its location in transverse section can be found by noting the boundary between the hypoglossal nucleus (a motor nucleus containing relatively large cells - motoneurons) and the nucleus solitarius (containing smaller cells). Using Atlas Figure 44, identify the hypoglossal nucleus, motor nucleus of X (labeled “dorsal efferent

43

nucleus of vagus) and the solitary nucleus (sensory for taste) and compare their positions in the open medulla with their positions in the closed medulla (Atlas Figure 42). Note that, although the absolute positions of the three nuclei have changed somewhat, their spatial relationships to one another have not. How to study the brainstem. In many ways the brainstem can be regarded as being organized segmentally with respect to its sensory inputs and motor outputs, much as the spinal cord is organized with respect to the spinal nerves. An important point is that a particular nucleus associated with a cranial nerve has only a sensory or motor function, whereas the cranial nerve itself may contain sensory or motor axons, or both. A given sensory nucleus in the brainstem will receive inputs from the cranial nerves that carry that particular type of sensory information, and the rostrocaudal extent of the nucleus will roughly correspond to the points of attachment of the cranial nerves that provide input to it. Thus, knowledge of the cranial nerves, their points of attachment to the brainstem, and their functions is the first step in understanding brainstem organization. In addition, many major ascending and descending fiber tracts occupy corresponding anterior/posterior and medial/lateral positions at different levels of the brainstem, and these tracts thus serve as useful landmarks.

Atlas Figure 60 is a good place to start. This is a Nissl-stained section running parallel to and just deep to the 4th ventricle. Using your knowledge of cranial nerves, first estimate their points of attachment to the pons and medulla and then look for cranial nerve nuclei with which they are associated. Note that the location of the sulcus limitans can be discerned beginning from the obex and coursing at about a 30 degree angle up the page; it can be identified by noting the difference in cell sizes between the larger motor cell bodiesi (located medially) and the smaller sensory neurons (located laterally); this is clearly seen in Atlas Figure 61..

Take as an example the nucleus solitarius. Find it in Atlas Figure 60 and compare its location in transverse sections 42-44. It receives sensory inputs from the gut and tongue (general and special visceral afferents, respectively) traveling in cranial nerves VII, IX and X, and it extends from the caudal medulla (level of attachment of the vagus nerve - X ) almost to the pontomedullary junction (level of attachment of the facial nerve - VII). Because nucleus solitarius is a sensory nucleus derived from the alar plate it is located dorsally, or more precisely dorsolaterally in the brainstem. Use as another example the abducens nucleus. This collection of large cells, easily seen in Atlas Figure 60, is located medially at the pontomedullary junctions where the 6th nerve attaches to the brain.

Use gross specimens as much as possible to understand the logic of cranial nerve attachments and cranial nerve nuclei. When using the Atlas, continually compare the sectional images to what you can observe on a gross specimen. Identify the same structure in the transverse sections as well as in other section planes. Actively construct an image in your own brain. Make a game of it! Do not try to memorize the Atlas.

44

MAJOR ASCENDING AND DESCENDING FIBER TRACTS Two major pathways decussate (cross the midline) in the caudal medulla. One is

the pyramidal tract whose crossed fibers become the lateral corticospinal tract in the spinal cord. The pyramidal decussation can be seen on the ventral surface of the medulla on a gross specimen, at the spinomedullary junction (Atlas Figure 6). Identify it also on Atlas Figures 40 and 74/75 . The continuity of axonal connection from cerebral cortex (internal capsule) through brainstem (crus cerebri and pyramidal tract) to spinal cord (lateral corticospinal tract) can be appreciated by examining Atlas Figures 23 and 24. Except for decussations, fiber tracts travel in straight lines, and hence their relative positions change only gradually, or not at all, from one level of the neuraxis to the next. In the caudal medulla locate the approximate positions of the spinothalamic tracts, the dorsal spinocerebellar tracts, and the gracile and cuneate fasciculi. What is the function of the lateral corticospinal tract? _____________________________________________(1) Where are the cell bodies of origin of the left corticospinal tract? ________________ ____________________________ (2)

A second major decussation that occurs at the caudal medulla involves the

axons of second-order cells conveying information to the thalamus about discriminative touch and proprioception. Axons in the posterior columns make their first synapse in the gracile and cuneate nuclei. Identify the location of these nuclei on a gross brain by following the gracile and cuneate fasciculi of the cervical spinal cord into the bulges on the dorsal surface of the medulla; identify them also on Atlas Figures 40-43 and 77. Axons of cells in these nuclei course ventrally to cross the midline (Atlas Figure 41, 42) and ascend to the contralateral thalamus as the medial lemniscus (Atlas Figure 44). In the caudal brainstem the medial lemniscus is located near the midline, but as it ascends it gradually moves laterally, eventually assuming a position adjacent to the spinothalamic tract at upper pontine levels. Compare its location in Atlas Figures 44 and 51. In Figure 77 it can be seen coursing over the basilar pons. Where are the cell bodies of the axons in the posterior columns? __________________________________(3) What sensations are mediated by cells in the gracile and cuneate nuclei? _________________________ ______________________(4) Do they represent the ipsilateral or contralateral side of the body? _____________________(5) What side of the body is represented by the left medial lemniscus? ______________________(6)

Near the midline of the medulla, you should locate the medial longitudinal fasciculus (MLF) in Atlas Figure 40 and 74 ( a particularly good view of it). This tract carries information that helps to coordinate head and eye movements, such as compensatory leftward eye movement during rightward head rotation. The MLF links eye muscle motor nuclei in the brainstem and spinal motoneurons controlling upper trunk and neck muscles (e.g., nucleus of the spinal accessory nerve - XI) with nuclei that receive information about head rotation from the vestibular labyrinth (i.e., cranial

nerve VIII B vestibulocochlear). On Atlas Figure 40 and 44 find the tectospinal tract

45

near the MLF. Tectum means 'roof' and consists of the superior and inferior colliculi lying on the dorsal surface of the mesencephalon. The tectospinal tract originates in the superior colliculus; it mediates reflexive orienting of the head, trunk and eyes to important visual or auditory stimuli (e.g., a bright flash of light or abrupt sound). What constitutes the cerebral peduncles of the mesencephlon? ____________________________________ (7)

BRAINSTEM RETICULAR FORMATION

Within the core of the medulla, pons, and mesencephalon lies a group of nuclei that are collectively known as the reticular formation (or reticular system, or reticular activating system). These are phylogenetically old structures having a wide range of functions, including general arousal (consciousness/unconsciousness), regulation of autonomic functions (such as blood pressure and respiration), regulation of sleep and wakefulness, and modulation of sensorimotor reflexes. These functions will be considered in detail in later lectures and future laboratory exercises. For now, identify the approximate location of the medullary reticular formation in Atlas Figure 44.

CRANIAL NERVE NUCLEI

Somatic motorneurons (general somatic efferent nuclei). Motorneurons of cranial nerves innervating skeletal muscle of the head and neck are located medially along the length of the brainstem; their medial (as opposed to ventral) location is due to the out-folding of the neural tube at the obex. Using Atlas Figure 60, note the locations of the hypoglossal nucleus, abducens nucleus, and the motor trigeminal nucleus. Find them in transverse sections 43, 48, and 49/50. Note that each of these nuclei are located in medial locations at the corresponding rostral-caudal levels where their respective nerves exit the brainstem. A small elevation, called the hypoglossal trigone, can be seen in gross specimens on the floor of the 4th ventricle; it is located medial to the sulcus limitans and corresponds to the location of the underlying hypoglossal nucleus. The vagal trigone, corresponding to the dorsal motor nucleus of the vagus (see next section), is located just lateral to it. The spinal accessory nucleus can be seen in the transverse section at the level of the pyramidal decussation (Atlas Figure 40) where it occupies a position similar to the anterior horn motorneurons in the spinal cord. The nucleus extends from the fifth or sixth cervical segment to about the middle of the pyramidal decussation in the medulla. .

Find the trochlear nerve on the gross brainstem just caudal to the inferior colliculus (see also Atlas Figure 5 ), and find the nucleus of the trochlear nerve in Atlas Figure 52/53. The trochlear nucleus, unlike all other brainstem cranial nerve nuclei,

46

innervates the contralateral side. The decussation of the axons occurs in the roof of the cerebral aqueduct. What ventricles are interconnected by the cerebral aqueduct? ____________ (8). The oculomotor nucleus is in a similar location more rostrally, near the superior colliculus; in Atlas Figure 54, the nerve can be seen exiting the brain in the mesencephalon. Visceral motorneurons (autonomic or general visceral efferent nuclei). Located just lateral to the somatic motorneuron nuclei, in a relative position corresponding to the intermediolateral cell column of the spinal cord (e.g., thoracic pre-ganglionic sympathetic neurons), are nuclei containing parasympathetic preganglionic neurons controlling smooth muscle and glandular secretion. They are termed “preganglionic” because they innervate neurons in the parasympathetic ganglia, not the effectors (smooth muscle, glands) themselves.

The visceral motorneuron nuclei are the dorsal motor nucleus of the vagus, innervating thoracic and abdominal viscera), the inferior and superior salivatory nuclei (innervating saliva glands) associated with the glossopharyngeal and facial nerves, respectively, and the Edinger-Westphal nucleus (innervating the lens of the eye) associated with the occulomotor nerve.

The nuclei are located at rostral-caudal levels appropriate to the exit of their associated cranial nerves. With the exception of the Edinger-Westphal nucleus, they are just lateral to the somatic motorneuron nuclei. They comprise an interrupted column near the midline of the brains stem (see Atlas Figure 76 for a good view). For example, find the dorsal nucleus of X in the transverse section of Atlas Figures 42-44 and, especially, in Figure 60. The inferior and superior salivatory nuclei are not discrete, but the general location of the inferior nucleus is indicated in Atlas Figure 46.

The Edinger-Westphal nucleus is part of the occulomotor nucleus, sometimes called the oculomotor complex (Atlas Figure 54). Where are spinal parasympathetic preganglionic neurons located?__________________________________________ (9)

Just dorsal to the motor nucleus of the vagus is a region called the area postrema, that lacks a blood brain barrier. The physical juxtaposition of the area postrema and the dorsal nucleus of the vagus suggests a possible functional relationship between the two. What is it? _________________________________________________________(10) Visceral sensory neurons (visceral afferent nuclei). In the embryonic spinal cord, the sulcus limitans demarcates the ventral (motor) grey matter from the dorsal (sensory) gray matter. The somatic and visceral motor nuclei described above lie medial to the sulcus limitans, whereas sensory cranial nerve nuclei of the brainstem lie lateral to it. The more medial of these are the visceral sensory neurons in nucleus solitarius that receive synaptic inputs from afferent fibers in cranial nerves VII, IX, and X. The rostral

47

two nerves mediate sensory function (taste) in the tongue and oral cavity, whereas axons in the vagus nerve provide sensory information from the thoracic and abdominal viscera. Identify its location on Atlas Figure 43 and note its position relative to the dorsal motor nucleus of X. Trace its rostrocaudal extent in Figures 42-44 and in Figure 60. Where is the tract of the nucleus solitarius relative to the nucleus itself? ________________________________ (11) Somatic sensory neurons (general somatic afferent nuclei). Cutaneous innervation of the face and head is supplied by primary afferent neurons mainly in the trigeminal ganglion (a structure analogous to a spinal cord dorsal root ganglion) and to a lesser extent from ganglia containing afferent neurons associated with the facial, glossopharyngeal and vagus nerves (we won’t be concerned with the ganglia containing their cell bodies).

The cranial nuclei receiving somatic sensory inputs are the principal (or main or chief) sensory nucleus and the spinal trigeminal nucleus. The principal sensory nucleus is located in the pons at the level of attachment of the Vth nerve. Locate the principal sensory nucleus in Atlas Figure 50 and note its lateral position relative to the motor trigeminal nucleus. Compare this with the horizontal section of Atlas Figure 60 where its entire rostrocaudal extent can be seen. Cells in the sensory nucleus receive inputs from afferent fibers transmitting information about discriminative (light) touch from the face. What cranial nerves provide input to the principal sensory nucleus? ___________________________________ (12)

Just caudal to the principal sensory nucleus is the rostral part of the spinal trigeminal nucleus; this nucleus extends caudally to the spinal-medullary junction where it is continuous with the substantia gelatinosa of the spinal grey matter. Fibers from the trigeminal nerve descend in the spinal trigeminal tract to synapse on cells there. Axons from nerves VII, IX and X also provide inputs to the spinal trigeminal nucleus along its rostrocaudal extent. Like the substantia gelatinosa, the spinal trigeminal nucleus mediates pain and temperature sensitivity. Locate the spinal trigeminal nucleus in Atlas Figure 48 (in the pons) and in Atlas Figure 41 (at the spinomedullary junction). Also identify the spinal trigeminal tract which is located just lateral to the nucleus. In the caudal medulla, where is the spinothalamic tract relative to the spinal trigeminal nucleus? _________________________ (13) The spinothalamic tract carries pain/temperature information from which side of the body? _______ _______ (14)

Axons from neurons in the principal sensory nucleus and the spinal trigeminal nucleus cross the mid-line and join with fibers in the medial lemniscus and spinothalamic tract, respectively. Review the location of these tracts. Where are the cell bodies of origin of the medial lemniscus? ___________________________ (15)

48

Primary afferent neurons that provide proprioceptive information from the face (i.e., jaw movement) are located in the mesencephalic trigeminal nucleus. Cells in this nucleus are unusual in that they are pseudo-unipolar, dorsal root ganglion cells that are located in the central nervous system, not in a peripheral ganglion. The mesencephalic nucleus is a slender column of cells in the lateral margin of the grey matter forming the floor of the fourth ventricle, extending from the level of the rostral border of the trigeminal entry zone to the rostral midbrain. The rostrocaudal extent of the mesencephalic nucleus is shown in Atlas Figure 59. Compare its location in this view with transverse sections in Figures 50 and 51. The central processes of some of the cells in the mesencephalic trigeminal nucleus contact motoneurons in the motor nucleus of the trigeminal nerve, providing sensory input to mechanisms that reflexively control the force of bite. Where are the cell bodies of first-order afferents mediating proprioceptive sensations for the lower extremity? ____________________________________(16) What tract contains their central processes? _______________________________________(17)

Special visceral motorneurons (efferent neurons of the head and face). Motorneurons innervating skeletal muscles are located in the nucleus ambiguus (associated with nerves X and XII), facial motor nucleus ( N. VII) and trigeminal motor nucleus (N. V). During development these motorneurons migrate to a ventral-lateral position in the brainstem where they constitute a discontinuous column of motorneuron nuclei in the medulla and pons. The single sagittal section in Atlas Figure 78 contains each of these nuclei. Find each of them in the transverse sections in Atlas Figures 43/44, 47 and 49.

The nucleus ambiguus, which is an anatomically poorly segregated collection of cells located just dorsal to the inferior olive, innervates striated muscle of the larynx and pharynx and is important in vocalization and swallowing. Nucleus ambiguus also provides some innervation to the heart. What other nucleus provides parasympathetic innervation to the heart? _____________________________ (18)

More rostrally, neurons in the facial motor nucleus innervate muscles of facial expression. The axons of the facial motorneurons course rostrally, and then loop dorsally and laterally over the abducens nucleus. Their passage over the abducens nucleus creates an elevation on the floor of the IVth ventricle called the facial colliculus. Find the facial colliculus on a gross brain specimen in which the floor of the 4th ventricle is exposed (see also Atlas Figure 5). The axons then go in a ventral direction back toward the facial nucleus, pass just lateral to it, and exit at the pontomedullary junction. The complicated course of these axons results from the ventral migration of the facial motoneurons (special visceral efferents) away from the lumen of the embryonic neural tube, trailing their axons behind them. Trace the course of these axons in Atlas Figure 48. Facial motor fibers innervate the muscles of facial expression, as well as the stapedius of the middle ear; contraction of this muscle dampens movement of the stapes bone and, thus, attenuates transmission of sound energy into the inner ear.

49

What three sensory nuclei receive inputs from axons in the facial nerve? _________________________________________ (19)

The motor nucleus of the trigeminal nerve contains large motor neurons that control the muscles of mastication (chewing). Again, note the spatial relationship between the principal sensory nucleus and the motor trigeminal nucleus in Atlas Figures 49 and 50. Sensory nuclei of the 8th nerve (auditory and vestibular afferents). Brainstem nuclei that receive sensory inputs from the vestibulo-cochlear nerve, sometimes described as special somatic afferent nuclei, are clustered in a group of laterally situated nuclei in the rostral medulla and caudal pons, near the attachment of the 8th nerve. On a gross specimen, locate this sensory nerve, which arises in the auditory and vestibular labyrinth deep within the temporal bone. Sounds stimulate the cochlear receptors, which communicate with the central nervous system via axons of the cochlear portion of the VIIIth nerve. The axons terminate in the dorsal and ventral cochlear nuclei, which can be seen in Atlas Figures 45 and 46. Projections of the dorsal and ventral cochlear nuclei to more rostral auditory brainstem nuclei may be crossed or uncrossed; hence, there is bilateral (binaural) representation of sound throughout most of the central auditory system. One of the major structures involved in auditory processing is the inferior colliculus.

Information about angular and linear of the head, transduced respectively by receptor cells of the semi-circular canals and otolith organs of the vestibular labyrinth, is transmitted to the central nervous system via axons of the vestibular portion of the VIIIth nerve. Near the level of entry of this nerve are four nuclei of the vestibular system (you do not need to know the specific names or locations of each of the nuclei). Note the approximate position of the vestibular nuclei in Atlas Figures.44-48.

THE CEREBELLUM

The brainstem contains many nuclei and fiber tracts associated with the cerebellum. The cerebellum is shown from its ventral surface in Atlas Figure 3 and in midsagittal section in Atlas Figure 4. The cerebellum consists of two hemispheres and an unpaired midline region called the vermis. Cerebellar peduncles are bundles of axons which convey inputs to and outputs from cerebellar neurons The attachment of the cerebellum to the pons by the cerebellar peduncles gives this region of the brainstem a distinctive appearance. Find the inferior and middle cerebellar peduncles on a gross specimen and in Atlas Figures 44-49. Note that the border between them is not distinct. The inferior and middle cerebellar

50

peduncles can also been seen in Atlas Figure 5 where the cerebellum has been removed.

The pontine nuclei in the basilar part of the pons are a major source of input to the cerebellum, e.g., Atlas Figure 49. These neurons receive inputs from the ipsilateral cerebral cortex. Their axons cross the midline and project to the contralateral cerebellum via the middle cerebellar peduncle. From which side of the cerebral cortex does the right cerebellum indirectly receive motor command information via the pontine nuclei? _______________(20)

The inferior cerebellar peduncle also conveys input to the cerebellum, but cells of

origin of axons in the inferior peduncle are in the spinal cord and medulla. Axons arise from the dorsal nucleus of Clarke, the lateral (or accessory) cuneate nucleus and the inferior olive. The lateral cuneate nucleus (which you should identify in Atlas Figure 43) is the homologue for the arm of the dorsal nucleus of Clarke. The continuity of the inferior peduncle with the spinal cord can be seen in Atlas Figure 26 (see also Atlas Figure 60). Locate the inferior olivary nucleus in Atlas Figures 42-45; inferior olivary neurons convey sensory (e.g., somatosensory, visual) and cerebral cortical output information. What fiber tract conveys proprioceptive information from the leg to the cerebellum? ______________________ ____________________(21) From which side of the body does the right cerebellar hemisphere receive sensory information? ________________(22)

On Atlas Figure 47 locate the deep cerebellar nuclei, nuclear groups situated in the core of the cerebellum. These nuclei (the dentate, interposed, and fastigial) are the major source of cerebellar output. Most of the axons from the deep cerebellar nuclei travel through the superior cerebellar peduncle located in the roof of the fourth ventricle (Atlas Figure 47). Axons in the superior cerebellar peduncle project to the contralateral thalamus and to the contralateral red nucleus. The decussation of the superior cerebellar peduncles occurs just caudal to the red nuclei (Atlas Figures 52, 54 and 63). Which cerebellar peduncle contains projections from the inferior olivary nucleus to the cerebellum? _______________________(23) Which side of the thalamus receives direct outputs from the right cerebellum? _________________________________(24)

51

Label as many structures listed below on the following diagrams of the brainstem as you can. Review them on the appropriate Brain Atlas sections if you have problems.

Superior Cerebellar Peduncle Middle Cerebellar Peduncle Inferior Cerebellar Peduncle Cerebral peduncle Superior and Inferior Colliculi Obex Facial Colliculus Hypoglossal trigone Sulcus limitans Vestibular area Trochlear nerve (IV) Cuneate Fasciculus Indicate the approximate rostral-caudal points of attachments of: Occulomotor Nerve Trigeminal Nerve Abducens Nerve Facial Nerve Auditory/vestibular Nerve Glossopharyngeal Nerve Vagus Nerve Spinal Accessory Nerve

52

53

REVIEW QUESTIONS LAB 4 (25) The medulla contains:

A. Vagal fibers B. Glossopharyngeal axons C. Nucleus solitarius D. Spinal trigeminal nucleus E. Principal sensory nucleus of the trigeminal

(26) The mesencephalon contains:

A. the occulomotor nucleus B. the medial lemniscus C. spinal trigeminal tract D. the facial colliculus E. principal sensory nucleus

(27) In addition to the trigeminal nerve, somatic afferent fibers in the spinal trigeminal

tract arise from the:

A. trochlear nerve B. glosssopharyngeal and hypoglossal nerves C. hypoglossal and vagal nerves D. hypoglossal and facial nerves E. vagus, glossopharyngeal and facial nerves

(28) Which of the following might occur following damage to the facial nerve?

A. Inability to smile B. Nausea C. Ringing sound in the ear D. Dry mouth E. Loss of taste on back of tongue

54

ANSWERS TO REVIEW QUESTIONS LABORATORY EXERCISE 4

Brainstem and Cranial Nerves 1. Commands for voluntary movement 2. Right frontal lobe/precentral gyrus 3. Dorsal root ganglia 4.Discriminative touch, proprioception 5.Ipsilateral 6.Right 7.All of the midbrain except the tectum. 8. 3rd and 4th 9. In sacral segments at a dorsal/ventral position corresponding to the intermediolateral cell column of the thoracic cord 10. Chemicals in bloodstream may induce a visceromotor response (i.e., vomiting) 11. The tract of the nucleus solitarius surrounds the nucleus. 12. V, VII, IX and X 13. Ventral (anterior) 14. Contralateral 15. Gracile and cuneate nuclei 16. Lumbar/sacral dorsal root ganglia 17. Gracile fasciculus 18. Dorsal motor nucleus of X

55

19. Principal sensory nucleus, spinal trigeminal nucleus, nucleus solitarius 20. Left 21. Posterior spinocerebellar tract 22. Right 23. Inferior cerebellar peduncle 24. Left 25. A, B, C, D 26. A, B 27. E 28. A, C, D

56

LABORATORY EXERCISE 5

Gross Anatomy of Diencephalon and Telencephalon

INTRODUCTION Structures that make up the diencephalon are important because of their functional relationship to the cerebral cortex and because of their role in general visceral, autonomic and endocrine functions. A major diencephalic structure, the thalamus, serves as a primary relay center in which sensory information is projected to specific areas of the cerebral cortex. The thalamus is also involved in sensory/motor integration, synchronization and desynchronization of the electrical activity of the cerebral cortex, and the regulation of attention. A second major diencephalic structure, the hypothalamus, is the principal subcortical center for the regulation of sympathetic and parasympathetic activities. The purpose of this exercise is to study in detail the structural and functional organization of the neocortex. At the end of today's exercise you should be able to: 1. describe the basic organization of the thalamus and its input to the cortex 2. recognize the major fiber pathways linking the cortex to other regions of the brain, including other regions within the cortex itself. 3. recall the gross morphology and functional areas of the cortex.

OVERVIEW OF DIENCEPHALON Two major structures of the diencephalon are the thalamus and the hypothalamus. As seen Atlas Figures 5, 14 and 25, the two thalami are bilaterally symmetrical egg-shaped structures, separated from each other by the third ventricle. The thalamus is made up of separate groups of neurons called thalamic nuclei. All sensory input coming to the cerebral cortex along major sensory pathways (with the single exception of the olfactory system) is relayed via one or more thalamic nuclei. The internal capsule, lying along the lateral aspect of the thalamus, contains thalamic fibers projecting to the cortex as well as the axons of cortical cells projecting to sites in the thalamus, brainstem or spinal cord. The second major structure of the diencephalon is the hypothalamus. This area helps regulate visceral and endocrine functions. The activity of the pituitary gland is also controlled in part by the hypothalamus. The gland is joined to the ventral aspect of the diencephalon, posterior to the optic chiasm.

57

Examine the inferior surface of the whole brain. Identify the olfactory bulbs and olfactory tracts, the optic nerves, optic chiasm and optic tracts. The area bounded by the optic tracts and the cerebral peduncles contains structures belonging to the hypothalamus, including the median eminence, infundibulum and mammillary bodies. Refer to Atlas Figures 3 and 22. The infundibulum is the stalk to which the pituitary is attached. Immediately surrounding the infundibulum is a convex eminence called the tuber cinereum. The zone forming the floor of the third ventricle is called the median eminence of the tuber cinereum. Use Atlas Figure 4 as a guide for locating structures in the hemisected brain. Locate the hypothalamic structures which you previously identified on the inferior aspect of the whole brain: 1) tuber cinereum (Atlas Figures 3, 6 and 10), 2) infundibulum (see also Atlas Figure 22) and 3) mammillary bodies. The thalamus and hypothalamus form the lateral wall of the third ventricle. The hypothalamic sulcus marks the limit between the thalamus and hypothalamus, and is found on the wall of the third ventricle. The rostral portion of the hypothalamus extends to the lamina terminalis and the caudal part includes the mammilary bodies. Find these areas on the hemisected brain using Atlas Figure 4 as a guide. Another major part of the diencephalon, located dorsally, is the epithalamus. It includes the pineal body, the habenular nuclei, and the striae medullares (Atlas Figures 63 and 73). These three structures are thought to be involved in mediating circadian rhythms, cyclic variations in physiologic function. The stria medullaris is a fiber tract that interconnects the habenular nuclei, located medially at the posterior end of the diencephalon, with the hypothalamus. It runs along the medial margin of the thalamus. The medial surfaces of the thalami on each side of the third ventricle are partially fused in about 80% of human brains, and this fused zone is called the massa intermedia (interthalamic adhesion). The anterior and posterior commissures are easily seen on a midsagittal section of the brain. The anterior commissure is a compact bundle of fibers that interconnects medial regions of the two temporal lobes (see Atlas Figures 12, 22 and 73). It is located at the same rostral-caudal level as the optic chiasm (see Atlas Figure 70). The posterior commissure is at the junction between the diencephalon and mesencephalon (Atlas Figure 63 and 73); it interconnects pretectal nuclei and mediates reflexive pupillary constriction in one eye when light is directed into the other eye. Name the most rostral boundary of the diencephalon. _______________________(1). What forms the floor of the third ventricle? ________________ ________________(2)

INTERNAL STRUCTURES OF THE CEREBRAL HEMISPHERES

58

Ventricles and Choroid Plexus The ventricle system is a deeply situated, interconnected series of spaces within the brain, containing CSF and the organs that form it. The ventricles pertinent to this exercise are the third ventricles, already described, and the lateral ventricles. See museum models for a 3-dimensional representation. There are two lateral ventricles, one per cerebral hemisphere. Rostrally, the bodies of the lateral ventricles lie side by side, separated by a thin membrane called the septum pellucidum (see Atlas Figures 4 and 14). The extremities of each lateral ventricle protrude into the far confines of each hemisphere's frontal, temporal and occipital lobes. These distal portions of the lateral ventricles are called horns, which are named according to their location within one of the lobes (i.e., occipital horn, temporal horn, etc.). Choroid plexus is usually found in the body and temporal horn of the lateral ventricle. The lateral ventricles communicate with the third ventricle via the paired ________________________(3). . Gray Matter The largest single collection of gray matter in the brain covers the hemispheres and is called the cerebral cortex. The other collection of telencephalic gray matter is collectively referred to as the basal ganglia. This term refers to deep seated (hence, basal) collections of cells (ganglia) which concern somatomotor function (the caudate nucleus, the putamen, and the globus pallidus) and limbic function (the amygdala, see below). The caudate nucleus indents and forms the lateral wall of the frontal horn anteriorly, but its size decreases as it extends posteriorly. The caudate eventually becomes attenuated until all that remains is a thin tail, which follows the curve of the temporal horn of the lateral ventricle downward and then forward into the temporal lobe. The tail of the caudate terminates near the nuclei of the amygdala. Examine the caudate on a series of horizontal and coronal sections of the brain in order to acquire an idea of its three-dimensional shape. What forms the lateral wall of the frontal horn of the lateral ventricle? ___________________________(4) Its medial wall? _________________________(5) In Atlas Figures 13 and 25 locate the putamen and the medially adjacent globus pallidus. The putamen and globus pallidus together are called the lentiform nucleus (due their lens-like shape). Note that anteriorly (Atlas Figures 11 and 21) the caudate and putamen are continuous, where together they are sometimes referred to as the striatum. The globus pallidus is divided longitudinally by a narrow band of white matter into an internal (medial) and external (lateral) segment. Note the relationship of the basal ganglia to the thalamus on horizontal and coronal sections. The caudate, putamen, and globus pallidus are important in motor control. The striatum is composed

59

of which structures? ____________________________________(6). The lentiform nucleus is composed of which structures? _________________________________(7). Recall that the caudate and putamen receive inputs from the cerebral cortex and in turn influence motor commands by sending it information via one of the thalamic nuclei (see below). Located in the rostral and ventral part of the diencephalon is the basal nucleus of Meynert (Atlas Figure 70). This nucleus contains large cholinergic neurons that project to all areas of the cerebral neocortex, the thalamus, the hippocampus and the amygdala. In the brains of Alzheimer's patients these cells degenerate, implicating their loss and the loss of the acetylcholine they provide in the etiology of senile dementia. A once obscure detail of neuroanatomy, the basal nucleus of Meynert has recently generated considerable interest because of its link to cognitive function and Alzheimer’s disease. Limbic System The term `limbic' lobe or system was originally used to describe the gray matter that forms a `border' around the forebrain consisting of the medial aspect of each hemisphere. This region includes the cingulate gyrus, parahippocampal gyrus, hippocampus, and amygdala. Because of their connections with these telencephalic structures, regions of the diencephalon are also included as part of the limbic system. These include the hypothalamus, septal region (zone in the rostral diencephalon near the nucleus basalis of Meynert), and the anterior nucleus of the thalamus. The limbic system is involved in a diversity of functions, including emotional behaviors that are essential for survival behaviors, such as the "four f's" (fighting, fleeing, feeding and reproduction), and the regulation of other motor and visceromotor behaviors through the autonomic nervous system. Components of the limbic system, in particular the hippocampal formation, are important also for learning and memory. Many circuits of the limbic system are loops linking telencephalic and diencephalic structures. The cingulate gyrus can be found above the corpus callosum on the medial side of the cerebral hemisphere. The cingulate gyrus receives inputs from the anterior nucleus of the thalamus (via the internal capsule) and sends output to the hippocampus by way of synaptic contacts with cells in the entorhinal cortex of the parahippocampal gyrus and nearby cortical areas. The hippocampus is an elongated structure, a few centimeters in length, that is located within the temporal lobe. It can be found along the floor of the temporal horn of the lateral ventricle (see Atlas Figure 25), and in cross section it is shaped somewhat like a flattened jellyroll. Find the hippocampus and related structures, such as the temporal horn of the lateral ventricle, the amygdala, and the parahippocampal gyrus, in Atlas Figures 23-29 and 82-83.

60

The hippocampus is connected with the hypothalamus and septal nuclei by a fiber tract called the fornix. Atlas Figure 29 shows the fornix emerging from the hippocampus (called the fimbria). From its attachment to the hippocampus on each side, the fornix follows the curve of the lateral ventricle. Just dorsal to the posterior aspect of the diencephalon the two fiber bundles unite and travel together, rostrally and medially, to the level of the foramen of Munro, where the fibers arch sharply ventrally and enter the hypothalamus as the columns of the fornix (see Atlas Figure Atlas Figure76). Try to follow the fornix in serial horizontal (Atlas Figures 9-15) and coronal sections (Atlas Figures 23-29). Note that the columns of the fornix are located near the septum pellucidum. Study the relationship between the hippocampus, tail of the caudate, and the temporal horn of the lateral ventricle in the temporal lobe. Also, using a 'scrap' hemisphere, dissect the temporal lobe to observe directly the hippocampus and fornix and their relationship to the lateral ventricle. (See an Instructor for assistance.) The hypothalamus has outputs to the brainstem and spinal cord, and to the anterior nucleus of the thalamus, via the mammillothalamic tract, which can be seen clearly in Atlas Figures 24 and 67. See also the excellent dissections in the blue folders in the lab. The anterior nucleus in turn projects to the ____________________________ (8) via the ______________________________(9). What part of the cortex relays information from the cingulate gyrus to the hippocampus? ________________________________(10) Review the location of the amygdala in the rostral part of the temporal lobe (Atlas Figures 22 and 68). Recall that it underlies a region of cortex called the uncus. The amygdala is interconnected with regions of the prefrontal and temporal cortex and with the septal and hypothalamic regions of the diencephalon. The pathway linking the amygdala in the temporal lobe with the diencephalon is the stria terminalis. This fiber tract runs along the groove between the thalamus and lentiform nucleus in the floor of the lateral ventricle (see Atlas Figures 65, 67-68). The amygdala also projects to the dorsomedial nucleus of the thalamus, which in turn sends output to prefrontal cortex, thus forming another looping circuit within the limbic system.

GENERAL ORGANIZATION OF THE THALAMUS

The thalamus is divided into several regions by an internal Y-shaped internal medullary lamina. The arms of the Y, located anteriorly, contain the anterior group of thalamic nuclei while its stem, which is angled in a dorsolateral to ventromedial direction, divides the rest of the thalamus into a dorsomedially situated medial group of nuclei and a ventrolaterally situated lateral group. Locate the internal medullary lamina in horizontal sections (Atlas Figures 14-15) and in coronal sections (Atlas Figures 24-27).

61

The lateral group of nuclei. The lateral group of nuclei is roughly divided in half into a lightly myelinated, dorsal "tier" of nuclei and a heavily myelinated, ventral "tier" of nuclei. The ventral tier of nuclei consists mostly of relay nuclei for specific sensory inputs to the sensory areas of the cerebral cortex and the relay to the motor cortex from the cerebellum and basal ganglia. From rostral to caudal these nuclei include the ventroanterior (VA) and ventrolateral (VL) nuclei (motor), ventroposterolateral (VPL) and ventroposteromedial (VPM) nuclei (somesthesis for body and face respectively), medial geniculate (audition), and lateral geniculate (vision). Each of these nuclei projects to its respective cortical region in a highly specific fashion and each in turn receives corticothalamic projections back from that region. The dorsal tier of nuclei within the lateral group consist of the lateral dorsal, lateral posterior and pulvinar nuclei. Each of the nuclei integrates information from a variety of subcortical and cortical centers. From rostral to caudal: the lateral dorsal nucleus projects to the posterior aspect of the cingulate gyrus; the lateral posterior nucleus projects to posterior parietal cortex; and the pulvinar receives visual inputs from the superior colliculus and pretectal areas and projects to occipital cortex. The medial group of nuclei. The medial group of nuclei, lying between the internal medullary lamina and the periventricular zone of the third ventricle, is associated with the olfactory and limbic systems and with association cortex of the frontal lobe. The major nuclear group here is the dorsomedial nucleus (see Atlas Figures 25, 63 and 65) which projects to prefrontal cortex via the anterior limb of the internal capsule. Regions of cortex within the frontal lobe are thought to be involved in emotional reactivity, personality, and certain aspects of cognition. Prefrontal lobotomy interrupts these projection fibers to frontal cortex and has profound effects on these functions. The anterior limb of the internal capsule lies between the _____________________ and the ________________________(11). The anterior group of nuclei. The anterior group, located between the arms of the Y formed by the internal medullary lamina, has its major connections with medial regions of the cortex, notably the cingulate gyrus. This projection is part of an integrative system which links various subcortical limbic structures with the frontal and temporal lobes by way of the anterior nucleus, cerebral cortex, hippocampal formation and mammillary bodies. The hippocampus projects to the mammillary bodies by way of the ___________________________________________(12). Recall that the latter, in turn, projects to the anterior nucleus via the mammillothalamic tract, which in the rostral thalamus occupies a position homologous to the internal medullary lamina. Note the location of the anterior nucleus in Atlas Figures 24 and 67 and the mamillothalamic tract in Atlas Figures 24, 67 and 77. The intralaminar nuclei. A group of nuclei is located within the internal medullary

62

lamina itself. The intralaminar nuclei receive widespread inputs from the brainstem reticular formation, the cerebellum and the spinal cord. Part of their output is thought to go to other thalamic nuclei and the rest to the cerebral cortex. Most of the intralaminar nuclei project to diffuse areas of the cortex and a single fiber may terminate in more than one cortical region. The intralaminar nuclei are often referred to as a non-specific projection system whose function may be to increase or decrease general excitability levels over widespread cortical regions.

ORGANIZATION OF THE INTERNAL CAPSULE The internal capsule is comprised of virtually all fibers that directly link the cerebral cortex to other levels of the neuraxis. These fibers arise from and project to the whole extent of the cerebral cortex; they course through the underlying white matter of the hemisphere and converge toward the diencephalon as a fan-shaped mass of fibers called the corona radiata. On reaching the diencephalon these fibers form a prominent compact bundle of axons called the internal capsule. The internal capsule is bounded medially by the thalamus and caudate nucleus and laterally by the lenticular nucleus. Fibers within the internal capsule interconnect the thalamus and cerebral cortex by thalamocortical and corticothalamic fibers. In addition to these fibers interconnecting thalamus and cortex, the internal capsule contains axons that descend from the cortex to lower levels of the neuraxis such as to the brainstem and spinal cord. These cortical efferent fiber systems are often referred to as corticofugal fibers. Smaller projections also exist to the hypothalamus, substantia nigra, red nucleus and basal ganglia. Below the level of the thalamus corticofugal fiber systems make up the crus cerebri of the midbrain. In Atlas Figures 10-17, 24-25 identify the internal capsule and observe how, together, the internal capsule, cerebral peduncles and medullary pyramids form a continuous fiber system extending from the cortex down to the spinal cord. On a horizontal section of the brain, e.g., Atlas Figure 14, note that anteriorly the internal capsule divides the lentiform nucleus from the caudate, and that posteriorly it divides the lentiform nucleus from the thalamus. These anterior and posterior arms of the internal capsule are called limbs; the bending point, or genu of the internal capsule, is located at a rostral-caudal level corresponding to the rostral aspect of the diencephalon. There is a topographic order to the internal capsule such that more rostral thalamic nuclei, which in general project to more rostral parts of the cerebral cortex, send their fibers through the more rostral aspects of the internal capsule. For example, corticospinal fibers leaving the precentral gyrus travel through the internal capsule just caudal to the genu, whereas fibers projecting to or exiting from somatosensory, auditory and visual cortical areas travel through progressively more caudal aspects of the internal capsule.

GROSS MORPHOLOGY AND FUNCTION IN THE CEREBRAL CORTEX

63

Gray Matter At the end of this exercise are outlines of the lateral and medial surfaces of the cerebral hemispheres which you should use in reviewing the following material. Label the following structures. 1. frontal, parietal, occipital and temporal lobes and their boundaries 2. sulci and gyri with which you are familiar (refer back to Exercise 1) 3. the motor, somatosensory, auditory, visual, gustatory, and olfactory areas including, where appropriate, the topographic representation within them 4. Broca's (frontal lobed) and Wernicke's (temporal lobe) language areas 5. corpus callosum, anterior commissure, posterior commissure, thalamus, lamina terminalis, medullary pyramids and pyramidal decussation. White Matter There are three major cortical fiber systems, all of them running more or less at right angles to each other. The internal capsule interconnects the cortex with structures at lower levels of the neuraxis, the corpus callosum interconnects the two hemispheres across the midline, and long association fibers interconnect rostral and caudal regions within a cerebral cortical hemisphere. You are already familiar with two of these major fiber systems, the corona radiata of the internal capsule containing cortical projection fibers and the corpus callosum which contains commissural fibers linking regions in the two hemispheres. The corpus callosum can be observed clearly in midsagittal sections of the brain. It is divided, anteriorly to posteriorly, into a rostrum, genu, body, and splenium (memory aid: closest to spleen). The corpus callosum interconnects homologous regions of the cortical hemispheres. Thus, fibers within the genu of the corpus callosum interconnect parts of the ________________________(13) lobe, fibers in its body connect regions of the____________ __________________(14) and _______________________(15) lobes, while regions of the temporal and occipital lobes are interconnected by commissural fibers traveling in the ________________________________(16) of the corpus callosum. Cortical association fibers interconnect different cortical regions within the same hemisphere. Short association fibers link nearby regions of cortex by via the white matter in the floor of each sulcus. For example, short association fibers include axons that interconnect motor and sensory areas in the pre- and postcentral gyri. Long association fibers connect cortical regions in different lobes of the same hemisphere. What sensorimotor function might be subserved by fibers connecting the frontal lobes

64

with the occipital lobes? ____________________________________(17) On the medial aspect of the hemisphere the cingulum (girdle) lies deep to the cingulate gyrus (Atlas Figure 79) and links regions of the frontal and parietal lobes with parahippocampal and adjacent temporal lobe areas of the cortex.

65

Figure 1

66

Figure 2

67

Label the structures listed below in the diagram on the next page.

Anterior commissure Mammillary bodies Aqueduct Massa intermedia (if present) Central canal of spinal cord Medulla Cerebral hemispheres Oculomotor nerve Cerebral peduncle Optic chiasma Superior and inferior colliculi Corpus callosum: rostrum, genu,

Pons body, and splenium Pineal gland Interventricular foramen Posterior commissure Lamina terminalis Fornix: body and column Septum pellucidum Fourth ventricle Tectum Hypophysis Tegmentum of midbrain and pons Hypothalamus Thalamus Infundibulum Third ventricle Vermis of Cerebellum

68

69

REVIEW QUESTIONS LAB 5

(18) Fiber projections from the hypothalamus to the anterior thalamic nucleus course in the _________________________ tract.

(19) What diencephalic nucleus has cholinergic projections to widespread areas of

the cerebral cortex? (20) Name four parts of the corpus callosum from rostral to caudal. (21) Name the telencephalic basal ganglia. (22) The largest group of projection fibers to and from the cortex is called _________

____________________. (23) A massive band of commissural fibers connecting the two hemispheres is called

___________________________. (24) The _____________ and ______________ form the lateral wall of the third

ventricle. (25) A fiber tract originating in the amygdala called the ____________ arches along

the medial border of the caudate nucleus. (26) Name three specific sensory relay nuclei in the thalamus

________________________, ________________________, and _________________________.

(27) Which thalamic nucleus receives input from the temporal lobe and projects to

frontal cortex? (28) The neocortical lobe having the fewest connections to the thalamus is _____________________________. (29) What thalamic nucleus relays information from basal ganglia nuclei to the

precentral gyrus?

70

ANSWERS TO REVIEW QUESTIONS LABORATORY EXERCISE 5

Gross Anatomy of Diencephalon and Telencephalon

1. Lamina terminalis 2. Median eminence 3. Foramina of Monro 4. Head of caudate 5. Septum pellucidum 6. Caudate and putamen 7. Putamen and globus pallidus 8. Cingulate gyrus 9. Internal capsule 10. Entorhinal cortex 11. Head of caudate and lentiform nucleus 12. Fornix 13. Frontal

14. Frontal 15. Parietal 16. Splenium 17. Integration of visual information with motor commands for voluntary eye movements

(frontal eye fields) 18. Mammillothalamic tract

71

19. Nucleus basalis of Meynert 20. Rostrum, genu, body, splenium 21. Caudate, putamen, globus pallidus (the amygdala is included as part of the basal

ganglia in some anatomical texts) 22. Internal capsule 23. Corpus callosum 24. Thalamus and hypothalamus 25. Stria terminalis 26. Ventral posterior, medial and lateral geniculate 27. Dorsomedial nucleus 28. Temporal lobe 29. Ventral lateral, ventral anterior

LECTURE OUTLINES

and

HANDOUTS