Hypothalamus

Marco CelioMai 2010

Plates from the seventh book of the first edition (1543) of the Fabrica by Andreas Vesalius, showing what is believed to be the oldest anatomical images in Western literature of the hypothalamic-pituitary unit.1) Enlarged view of the pituitary gland (A), hypothalamic infundibulum (B) and ducts comprising the foramen lacerum and superior orbital fissure (C, D, E, F) believed to drain the brain mucus or phlegm (in Latin pituita) from the pituitary gland to the nasopharynx; 2) anatomical relationships between the infundibulum(D), the dural diaphragma sellae (F), the internal carotid arteries (C, D) and the oculomotor nerve.

Drawings by Leonardo da Vinci (1508-1509) taken from the Codici di Anatomia of the Windsor’s Collection(A) Inferior surface of the brain, showing the rete mirabilis (arrow) that surrounds the pituitary gland; (B) three-dimensional representation of the cerebral ventricles. The third ventricle (3v) was believed to be thesite of afference and elaboration of the "sensus communis” (Latin for peripheral physical sensations)

Historical

• John Newport Langley (1852-1925)– Introduced

• the term autonomic nervous system• the concept of antagonism between sympathicus

and vagus• and discovered preganglionic and postganglionic

cells

Historical

Historical

• Walter Bradford Cannon (1871-1945)• Circuits in the central nervous system are responsible for the integrative action of the

autonomic nervous system• Cannon was influenced by the Harvard philosopher William James according to

whom the emotional state of an organism is associated with afferent feedbacks from the body, notably from vascular and visceral structures

• Cannon proposed that the different emotional states are represented in the brain rather being peripheral in origin and are expressed by changes of activity in the sympathetic and parysympathetic nervous system

• Cannon view of the autonomic nervous system was that of a system designed to preserve life during grave physical crisis requiring extreme efforts (« fight or flight »)

• Writes the book: « The wisdom of the body »• Introduces the concept of « homeostasis » • Parasympathetic system conserve body energy

Claude Bernard: « le milieu intérieur »

• Walter Rudolf Hess (1881-1973)• Observed the behavior elicited in conscious

cats by local electrical stimulation of the hypothalamus• Transferred the idea of a dichotomy of the functional organization of

the autonomic nervous system to the hypothalamus• Rostral part: integrate somatic, autonomic and endocrine reactions

• Promote revovery and conservation of energy, digestion, excretion and evacuation of waste as well as reproductive function – parasympathetic nervous system -- trophotrophc reaction

• Caudal part: general activation of the sympathetic nervous system• Mobilization of body energy and enhancement of performance capacity (ergotropic reaction)

Whereas earlier studies found that electrical stimulation or lesions in the hypothalamus profoundly affect autonomic function, more recent investigation have demonstrated that

many of these effects are due to the involvement of descending and ascending pathwaysof the cerebral cortex or the basal forebrain passing through the hypothalamus.

Historical

Hypothalamus

• 1% of brain volume (4 gr)• connected to all part of the nervous

system (2’000 projections)• 50 to 100 different group of neurons

(nuclei)• Masterplan similar in all mammalian

Characterized by the projection of their axons, their synaptic inputs and their histochemistry

Axonal tracing

Immunohistohemistry(in-situ hybridisation)

The hypothalamus integrates autonomic and endocrine functions with behavior

The hypothalamus serves this integrative function be regulating six basic principal needs:– blood pressure and electrolyte concentration – body temperature– energy metabolism– reproduction– emergency responses (stress)– emotional response

Drinking and salt appetite, maintenance of blood osmolality and vasomotor tone

Control of metabolic thermogenesis andbehaviors such as seeking a warmer or cooler environmentBy feeding, digestion andmetabolic rate

Through hormonal controlof mating, pregnancy and lactation

Blood flow to muscleand other tissues and secretion ofadrenal stress hormones

The hypothalamus regulates these basic life processes by recourse to 3 main mechanisms

• Receiving sensory information from virtually the entire body. Direct inputs from the retina, olfactory system and visceral sensory system. Inputs from the circumventricular organs. Internal sensory neurons responsive to changes in temperature, osmolality, glucose and Na+.

• Comparing sensory information with biological set points (temperature, osmolality, Na+, etc.)

• Adjusting deviations from a set point by an array of autonomic, endocrine and behavioral responses.

If the body is too warm the hypothalamus intervene by: • shifting blood flow from deep to cutaneous vascular beds • increasing sweating and heat loss through the skin • increasing vasopressin secretion to conserve water for sweating • activating coordinated behaviors (seeking a cooler environment)

Homeostasis / Allostasis

• Stability of systems that maintain life– pH– concentration of

different ions in the extracellular fluid (Na+, Ca2

+)– osmolality of

extracellular fluid– glucose levels– arterial oxygen tension

• Adaptation to changing external and internal environment– arterial blood pressure– heart rate– body core temperature– concentration of

circulating hormones– sleep-wake cycle– energy metabolism

Constantly present Temporary process, e.g. under stress

Circumventricular organs

Area postrema

Blood capillary with fenestrated endothelium and a wide perivascular space. They are typical in circumventricular organs. L - lumen, blue arrow - endothelial pore, red arrow - basal lamina, P -perivascular space, F - fibrocyte. Inset: blood capillary with the wide perivascular space. Scale = 200 nm. (Rat, area postrema.)

7/13/00 J S k

Blood – brain barrier

Blood-brain barrier absent

InputsHypothalamic afferences

OutputPituitary

ependymal zone (E), internal zone (ZI), and external zone (ZE)

Fibers coursing through the ZI are vasopressin positive

Fibers terminating in the ZE in close association to portal capillaries (PC) are TRH-positive

Median eminence

Vasopressin- Somatostatin

Vasopressin

Somatostatin

OutputSympathetic division

OutputParasympathetic division

Outputprojections from the PVN

Hypothalamus

• Subdivided in three longitudinal zones– Periventricular, medial and lateral

• Rostrocaudally divided in• anterior, tuberal and posterior (mammillary) part

• Based on patterns of connectivities subdivided in

– Neuroendocrine motor zone: contains the endocrine motor neurons relted to posterior and anterior pituitary

– Circadian timing generator: organizes the temporal structure of hypothalamis functions – Pattern generating network: coordinates endocrine and autonomic patterns– Behavior control column: regulation of defensive, ingestive (nutrition and fluid balance),

reproductive and thermoregulatory behavior.

Sagittal section

Frontal section

Frontal sections

Intermingling of nerve cells

A pair of photomicrographs illustrating the distributionof oxytocin and vasopressin neurons in the human paraventricular nucleus.. Scale = 250 μm.