Early Experience and Developmental Learning

Overview

• Increasing differentiation of areas of cortex

• Infant is born during height of brain development

• Tertiary sulci develop from 1 month before to 12 months after birth

Four (very brief) Levels of Brain Development

Creation of a tube

Neural migration

• Many elements of initial neural migration specified genetically

• By 20 weeks gestation, 100 billion neurons! 50,000 – 500,000 neurons per minute

• Neurons follow path of glial cells outward from ventricles– To form 6 layers of cortex

Neural development: Synaptogensis

• Once in place, synapses are overproduced somewhat haphazardly– 1 year old has 150% more synapses than adult

• These are pruned (diminish) during development• Repetition of sensory-motor patterns create more

specific set of experience dependent synaptic linkages

Increase in complexity of neural connections

Like a growing forest

How do the correct synapses form?

• 15,000 synapses for every cortical neuron– 1.8 million per second in first 2 years!

• Cerebral cortex triples in thickness in 1st year

• Sensory and motor neurons must extend to correct brain are and form correct synapses

• This quantity of information cannot be genetically micro-managed

Three models

What does individual development look like?

Individuals Group

Two Types of Experience in Brain Development

• Experience-expectant• Experience dependent

Experience-expectant• How common early experiences provide essential

catalysts for normal brain development – Early visual stimulation, hearing, exposure to language,

coordinating vision and movement,

• The developing brain “expects” and requires these typical human experiences, and relies on them as a component of its growth.

Experience-dependent

• How individual experience fosters new brain growth and refines existing brain structures

• Can be unique to an individual– Reading– Singing, music

Neural Darwinism (Edelman)

• Use it or lose it– What is not used, is pruned– What is used, develops stronger connections

• Organism & environment are system that shapes brain– Brain development is guided by environment

• Brain enables behavior which shapes brain– Synaptic development is not teleological

The fetus as constructing its own development

• Fetal behavior impacts physical development– In chicks prevented from moving, cartilage turns

to bone• Fetal sensory experience impacts sensory

development– Mice whose tongues were anesthetized had

malformed cleft palates

Prenatal sensory experience impacts sensory development

• Hearing typically develops before sight• Rats, ducklings, and quail chicks exposed to visual

stimulation prenatally– before they normally would

• lose hearing ability at birth

Normal sensory development contingent on extra-fetal environment

• Differences in the timing of augmented prenatal stimulation led to different patterns of subsequent auditory and visual responsiveness following hatching.

• No effect on normal visual responsiveness to species-typical maternal cues was found when exposure to tactile and vestibular stimulation coincided with the emergence of visual function (Days 14-19)

• When exposure took place after the onset of visual functioning (Days 17-22), chicks displayed enhanced responsiveness to the same maternal visual cues.

• When augmented tactile and vestibular stimulation coincided with the onset of auditory function (Days 9-14), embryos subsequently failed to learn a species-typical maternal call prior to hatching.

• Honeycutt, H. & R. Lickliter (2003). Developmental Psychobiology 43: 71-81. The influence of prenatal tactile and vestibular stimulation and visual responsiveness in bobwhite quail: A matter of timing

Prenatal behavioral development

• 9 weeks - movement• 16 weeks - frowning, grimacing• 25 weeks - moves to drumbeat• 26 weeks - remembers sounds• 32 weeks - all brain areas functioning • 34 weeks - can habituate

1st Trimester• Behavioural Repertoire:

– 8 weeks: Startle (arms and legs shoot outward)– 9 weeks: “graceful” general movements of the head, trunk, limbs– 10 weeks: Stretch (head moves back, trunk arches, arms lifted)– 11 weeks: Yawning

• Cause and Function of Prenatal Movement– Unable to inhibit movement; inhibition comes with the connection to

higher brain centres– Fetal movement is necessary for the physical systems to develop

normally (stimulate development of muscles, tendons, ligaments);– Breathing movement important for lung development– Changes in position may promote better circulation & help prevent skins

from sticking together– Motor behaviour moves amniotic fluid

• structural growth of fetus– Some behaviours (e.g., sucking) may be preparatory

» http://web.uvic.ca/psyc/coursematerial/psyc435a.f01/435A/Week%202%20Lecture%20Notes.pdf

Role of experience

Overview of brain growth

• Subcortical areas responsible for reflexes develop first– E.g. spinal cord

• Followed by cortical areas in a specific progression – What is most human develops last

• Most but not all neurons present at birth– Synapses develop– Myelin develops

At the same time - Myelination

• Fatty sheaths develop and insulate neurons• Dramatically speeding up neural conduction• Allowing neural control of body

– General increase in first 3 years is likely related to speedier motor and cognitive functioning

• allowing activities like standing and walking

• Endangered by prenatal lead exposure

“Promoting early brain development”?

• Re-discovery of importance of early experience– “How brain connections grow and change as a

result of stimuli from the environment. – How early stress can be harmful to the

developing brain. – Principle of "use it or lose it" – Seven ways to support brain development:

• http://www.pitc.org/

“Considerable misunderstanding of early brain development occurs when neurons and synapses are considered independently of the development of thinking, feeling, and relating to others.”–Thompson, 2001, p. 29

Is it all over after 3?

• Is the course of development set in infancy? • Early experience is important• But, with some exceptions, human beings remain

open to the positive effects of additional experience – The same is true for the impact of experience on brain

development • How important is it to ‘stimulate your child’s brain’?

What kind of stimulation is best?

• Running rats …• Adult neurogenesis …

Implications for practice

• It is important to provide a safe, warm, supportive, stimulating environment for infants

• But its never too late to improve developmental outcome for an individual

• At any point, current conditions are as important as past conditions

• No flashcards

Brain Overgrowth in the First Year of Life in Autism

• The clinical onset of autism appears to be preceded by 2 phases of brain growth abnormality: a reduced head size at birth and a sudden and excessive increase in head size between 1 to 2 months and 6 to 14 months. Abnormally accelerated rate of growth may serve as an early warning signal of risk for autism

• Courchesne, Carper, Akshoomoff, (2003)

• Why overgrowth?

• Later developing processes more susceptible to the effects of experience

• Motor development more plastic than language development

• Sensitive periods• Genetics and experience: Indissoluble

Synapse Rearrangement

•Active synapses likely take up neurotrophic factor that maintains the synapse

•Inactive synapses get too little trophic factor to remain stable

Synapse Rearrangement

Time-lapse imaging of synapse elimination

Two neuromuscular junctions (NM1 and NMJ2) were viewed in vivo on postnatal days 7, 8, and 9.

Myelination

MYELIN AND SALTATORY CONDUCTION

Myelin is an electrical insulator sheath wrapped around axonsOligodendrocytes produce myelin on CNS axonsSchwann cells produce myelin on PNS axonsShort gaps in myelin along axons called nodes of Ranvier

Myelin’s function is to speed action potential propagation down long axons

MYELIN SHEATH COMPOSED OF MANY LOOPS OF A GLIAL PROCESS

Each oligodendrocyte has severalprocesses, each of which producesa myelin sheath on a different axon

Schwann cells each form only asingle myelin sheath

MYELIN SHEATH GENERATED BY CONTINUED MIGRATIONOF PROCESS LEADING EDGE AROUND AXON

While the leading glial process continues to encircle the axon,the earlier-formed loops undergo compaction

to form the contact myelin sheath

MYELINATED FIBERS VIEWED IN CROSS-SECTION

Low magnificationLight microscopy

High magnificationelectron microsopy

Electron microscopy at very high magnification reveals alternatingmajor dense lines andintraperiod lines

ORGANIZATION OF THE MYELIN REPEAT PERIOD

PLP is the most abundant protein in CNS myelin

P0 is the most abundant protein in PNS myelin

THE PARANODE IS SITE OF TIGHT AXON-GLIAL ADHESIONS

ROLE OF MYELIN IN FAST ELECTRICAL TRANSMISSION

UnmyelinatedAxon(SLOW CONDUCTION)

MyelinatedAxon(FAST CONDUCTION)

Action potential at one point along unmyelinated axon produces current that only propagates short distance along axon, since current is diverted through channels in axon membrane. So action potential can only next occur short distance away

Myelin reduces effective conductance and capacitance of internodal axon membrane.Action potential at node of Ranvier produces current that propagates0.5-5 mm to next node of Ranvier, generating next action potential

SODIUM CHANNELS ONLY AT NODESAT VERY HIGH DENSITY

THIN AXO-GLIAL SPACE AT PARANODE LOOPS CREATES HIGHNODE-INTERNODE PERIAXONAL RESISTANCE WHICHELECTRICALLY ISOLATES INTERNODAL MEMBRANE

Only 20 Angstrom gap betweenmature paranodal loopand axonal membrane

Tight junctions betweenmature loops

Raxial

Rparanode

Raxial

Rparanode

NODE NODEINTERNODEPARANODE PARANODE

SINCERparanode >>>> Raxial & RleakCHARGING OFINTERNODALMEMBRANEVERY SLOWAND CHANGEIN INTERNODEVM ISINSIGNIFICANT

POTASSIUM CHANNEL SHUNT NOT REQUIRED INMOST MATURE MYELINATED AXONS

Myelinated axons conduct action potentials at ~ 50 mm/msec

Total refractory period of nodal Na+ channels after inactivationis ~ 5 msec.

Therefore, by the time Na+ channels return to rest after an action potential, the spike has propagated 25 cm away(which is terminated in most cases)

K+ channel inhibition in mature myelinated fibers does not alter conduction or promote misfiring.

FORMATION OF NODAL, PARANODAL, AND JUXTANODALPROTEIN CLUSTERS DURING MYELINATION

Kv1

Kv1

• Na+ channels cluster early at wide immature nodes. As nodes narrow andmature, Na+ channel density increases.

• K+ channels cluster later and shift their position. They first appear at nodes,But move to paranode and then juxtaparanode as structure matures.

• K+ CHANNELS ARE OF CONTINUED IMPORTANCE DURING MATURATION OF MYELIN,SINCE ONLY FULLY MATURE FIBERS CONDUCT FAST ENOUGH TO MAKE THEM UNNEEDED.PERSISTENCE OF K+ CHANNELS IN MATURE JUXTAPARANODES MAY FUNCTIONALLYPROTECT FIBERS IN CASE OF PARTIAL DE-MYELINATION

MUTATIONS CAN CAUSE MINOR OR MAJOR MYELIN LOSS

“SHIVERER” mutant mouse has almostcomplete absence of myelination,due to a failure of precursor cellsto differentiate into oligodendrocytes

Other mutations which impairmyelination are mutations in themajor protein components ofthe myelin sheath

MUTATIONS IN PLP GENE CAUSING HYPOMYELINATION IN CNS

Similarly, structural mutations in PNS myelin protein genescause defective myelination of the PNS

Myelination Lasts for up to 30 Years

Brain Weight During Development and Aging

Critical Periods

Sensitive PeriodAnatomy and physiology are especially sensitive to

modulation by experience.Critical PeriodAn extreme form of Sensitive Period.Appropriate expression is essential for the normal

development of a pathway or set of connections (and after this period, it cannot be repaired).

e.g., There was a critical period for the formation of ocular dominance columns, based on neuronal activity/input from both spontaneous firing and visual inputs from the eyes.

If appropriate information is not received during the critical period (from experience), this pathway never attains the ability to process information in a normal fashion, and as a result, perception or behavior can be permanently impaired.

E.g., development of appropriate social and emotional responses to others.

E.g., development of language skills in humans.

Models of Developmental Learning and the Importance of Early Experiences

1. Sound localization in the owl. - a “map” of auditory space is developed in the midbrain of the barn owl.

- This map integrates auditory and visual info so that movements of the eyes and head can be oriented towards auditory stimuli (and catch mice and rats!).

To create a map of auditory space, the midbrain nucleus has to learn (of inferior colliculus) spatial cues based on auditory signals it receives from the 2 ears.

Auditory space map and its inputs

What are the cues?Differences in timing and in the level (and pitch) between the 2 ears.

Why are these things not just genetically encoded?Individual differences in size, shape of head, sensations and speed of head movement, etc.

In young animals, this plasticity allows the pathway to respond and adjust to change or disruptions (e.g., growth, damage to ear, etc.).

Tuning of inferior colliculus neurons is adjusted in response to visual cues.

The location of plasticity is the ICX (external nucleus of the inferior colliculus).

If a stable shift in visual field occurs during the critical period (i.e., owls raised with prisms over their eyes), the auditory receptor field of the icx will realign with the shifted visual field.

Now, the owl will have (correctly coordinated visual/auditory stimuli with the prisms on).

The sensitive period for the owl, during which large shifts can occur, is throughout juvenile life (until reaching sexual maturity).

The experience induces the growth and elaboration of axons into the icx to sites where they can support appropriate responses.

This response depends upon activation of NMDA receptors (involved in plasticity).

Note: in our example, the power of genetically programmed pattern is still great (though an adult owl cannot adjust to a large shift in visual field, one that has been shifted can return to normal in the adult (over a period of weeks) when the prisms are removed.

NMDA receptors

Plasticity of axons in the ICX

2. Development of Birdsong.A special form of communication developed by

birds to i.d. their own, defend territories, or attract mates.

Birdsong is complex and has a periodic structure (like music).

“Dialects” or varieties of song can specify a geographic area, where the basic song structure is common to a species.

Song is developed by a combination of genetic instructions and learning (early experiences). The latter often takes place during a critical period.

1) Characteristics of song learning.*How can the extent of the critical period be determined in a species?

[raise birds in acoustic isolation and expose them to song for brief periods at different points of development]

“Isolate song”: a flat, species-specific pattern with complexity that a bird can develop if raised in isolation during the critical period.

“Developmental song”: abnormal pattern developed in a bird that is unable to hear itself and get auditory feedback during critical period.

2 major pathways for birdsong learning

Birdsong characteristics

2) Shows importance of a critical period during song memorization (learning songs of conspecifics: 2-8 weeks).

3) Illustrates importance of critical period during vocal learning (bird hears and evaluates his own song so that it matches the memorized song pattern).

[auditory feedback is essential for shaping the pattern of connectivity in the song-production pathway]

• Importance of genetic background for the types of patterns that can develop:- note isolate song (earlier)- what does a baby bird develop when raised with an alien (other species) birdsong during the critical period for memorization?

[genetically detrimental “filters” within pathway are responsible for song memorization].

If too distinct from normal, isolate song develops.Regarding song memorization, the critical period is closed

after the appropriate stimuli have been received.After 8 weeks plasticity decreases; So, stimulus must be

prolonged and rich (i.e., live bird and not a recording) for any memorization to occur.

Closure of critical period and decreased plasticity are also related to sexual maturity.

*What happens if a bird receives testosterone early? (song is fixed in “immature” state).

*What happens if bird is castrated prior to learning to sing?

[song production inconsistencies and unstable for rest of life – critical period never closes?]

Neural Pathway for Song LearningStill an active area of researchWe know a little regarding song production in species

when only males sing (*how is this studied?)

[Sexual dimorphism]Song System – 2 groups of nuclei:Motor – posterior forebrain: song productionFeedback – anterior forebrain: oral learningPosterior pathway: - necessary for products of

learned sounds. Higher visual center (HVC) RA arhistriatum hypoglossal nucleus:

motor neurons centrallyvocal muscles.

Anterior pathway: neurons respond maximally to bird’s own song.

HVC “area X” DCM (a thalamic nucleus) LMAN (lateral magnocellular nuc of ant striatum)

Sexual dimorphism-song nuclei

Sexual DimorphismIn Mammals:

A lesion in LMAN during critical learning period “freezes” song much like early testosterone.

However, lesions in adult birds after learning is complete have zero effect.

LMAN then sends input to RA hypoglossal n. muscles mediated by NMDA receptors.

These synapses will compete selectively and several will be eliminated just prior to closure of critical period (as sex hormones rise).

3. ImprintingLearning of cues through i.d. a parent –

important for survival involves learning multiple sensory cues that i.d. the parent (visual, auditory, olfactory, etc.) during brief critical periods.

Recall the classic experiment by Konrad Lorenz (“mother goose”).

Critical periods can be brief and can begin shortly before birth in some species.

What happens if baby is in isolation during critical period? [never responds appropriately to social signals from members of its own species].

What happens when raised by another species?What is the genetic filter here?During the (critical) imprinting period, a duck will

choose a duck over another species, or the closest equivalent (i.e., goose > human).

One Neural PathAuditory stem nucleus of anti forebrain activated as in previous examples of selective elimination of inputs occurs during late critical period in response to experience.

Binocular VisionAbility to “fuse” the image from 2 eyes to create

a 3-D image with depth.The consequence of visual inputs onto neurons of

the visual cortex is guided by early experience.A critical period exists, during which monocular

deprivation can prevent the development of stereoscopic vision.

Review the development of the ocular dominance columns for the projection of LGN to Layer IV of visual ctx.

Critical period for binocular vision development

Equal input from both eyes equally wide columns with competition based on neural activity:

If 1 eye is occluded, open eyes inputs are pruned and activity of majority of visual ctx is driven by LGN afferents from normal eye.

*Competition is driven by: amount of neural activitydegree of synchrony

Therefore, the stimulation of both optic nerves with equal but asynchronous stimuli one dominating , and impaired binocular vision.

Amount and synchrony of synaptic activation shapes the synaptic function and architecture by adjustments in synaptic strength through a process depending on activation of NMDA receptors: LTP.

*Rats: This dual process is not as rapid and plastic as the other examples we have reviewed. Disruption are not completely universal during critical period and patterns are not as ‘pre-set’.