1. Early Experience and Developmental Learning

2. 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

3. Four (very brief) Levels of Brain Development

4. Creation of a tube

5. 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

6. 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

7. Increase in complexity of neural connections
                                            
                                            
                                            
Increase in complexity of neural connections
Like a
growing
forest

8. 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

9. Three models

10. What does individual development look like?
Individuals
Group

11. Two Types of Experience in Brain Development
Experience-expectant
Experience dependent

12. 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.

13. Experience-dependent
How individual experience fosters new brain growth and refines existing brain structures
Can be unique to an individual
Reading
Singing, music

14. 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

15. 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

16. 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

17. 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: The influence of prenatal tactile and vestibular stimulation and visual responsiveness in bobwhite quail: A matter of timing

18. 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

19. 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

20. Role of experience

21. 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

22. 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

23. “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:

24. “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

25. 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’?

26. What kind of stimulation is best?
Running rats …
Adult neurogenesis …

27. 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

28. 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?

29. Later developing processes more susceptible to the effects of experience
Motor development more plastic than language development
Sensitive periods
Genetics and experience: Indissoluble

30. Synapse Rearrangement
Active synapses likely take up neurotrophic factor that maintains the synapse
Inactive synapses get too little trophic factor to remain stable

31. 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.

32. Myelination

33. MYELIN AND SALTATORY CONDUCTION
Myelin is an electrical insulator sheath wrapped around axons
Oligodendrocytes produce myelin on CNS axons
Schwann cells produce myelin on PNS axons
Short gaps in myelin along axons called nodes of Ranvier
Myelin’s function is to speed action potential propagation down long axons

36. MYELIN SHEATH COMPOSED OF MANY LOOPS OF A GLIAL PROCESS
Each oligodendrocyte has several
processes, each of which produces
a myelin sheath on a different axon
Schwann cells each form only a
single myelin sheath

37. MYELIN SHEATH GENERATED BY CONTINUED MIGRATION
OF 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

38. MYELINATED FIBERS VIEWED IN CROSS-SECTION
Low magnification
Light microscopy
High magnification
electron microsopy
Electron microscopy at
very high magnification
reveals alternating
major dense lines and
intraperiod lines

39. ORGANIZATION OF THE MYELIN REPEAT PERIOD
PLP is the most abundant protein in CNS myelin
P0 is the most abundant protein in PNS myelin

40. THE PARANODE IS SITE OF TIGHT AXON-GLIAL ADHESIONS

41. ROLE OF MYELIN IN FAST ELECTRICAL TRANSMISSION
Unmyelinated
Axon
(SLOW CONDUCTION)
Myelinated
Axon
(FAST CONDUCTION)
SODIUM CHANNELS ONLY AT NODES
AT VERY HIGH DENSITY
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 propagates
0.5-5 mm to next node of Ranvier, generating next action potential

42. THIN AXO-GLIAL SPACE AT PARANODE LOOPS CREATES HIGH
NODE-INTERNODE PERIAXONAL RESISTANCE WHICH
ELECTRICALLY ISOLATES INTERNODAL MEMBRANE
Tight junctions between
mature loops
Only 20 Angstrom gap between
mature paranodal loop
and axonal membrane
SINCE
Rparanode >>>> Raxial & Rleak
CHARGING OF
INTERNODAL
MEMBRANE
VERY SLOW
AND CHANGE
IN INTERNODE
VM IS
INSIGNIFICANT
Rparanode
Rparanode
Raxial
Raxial
NODE
PARANODE
INTERNODE
PARANODE
NODE

43. MOST MATURE MYELINATED AXONS
POTASSIUM CHANNEL SHUNT NOT REQUIRED IN
MOST MATURE MYELINATED AXONS
Myelinated axons conduct action potentials at ~ 50 mm/msec
Total refractory period of nodal Na+ channels after inactivation
is ~ 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.

44. FORMATION OF NODAL, PARANODAL, AND JUXTANODAL
PROTEIN CLUSTERS DURING MYELINATION
Kv1
Kv1
Na+ channels cluster early at wide immature nodes. As nodes narrow and
mature, 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 FUNCTIONALLY
PROTECT FIBERS IN CASE OF PARTIAL DE-MYELINATION

45. MUTATIONS CAN CAUSE MINOR OR MAJOR MYELIN LOSS
“SHIVERER” mutant mouse has almost
complete absence of myelination,
due to a failure of precursor cells
to differentiate into oligodendrocytes
Other mutations which impair
myelination are mutations in the
major protein components of
the myelin sheath

46. Similarly, structural mutations in PNS myelin protein genes
MUTATIONS IN PLP GENE CAUSING HYPOMYELINATION IN CNS
Similarly, structural mutations in PNS myelin protein genes
cause defective myelination of the PNS

47. Myelination Lasts for up to 30 Years

48. Brain Weight During Development and Aging

49. Critical Periods

50. Sensitive Period Anatomy and physiology are especially sensitive to modulation by experience. Critical Period An 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.

51. 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.

52. Models of Developmental Learning and the Importance of Early Experiences
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.

53. Auditory space map and its inputs

54. 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.

55. 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).

56. 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.

57. NMDA receptors

58. Plasticity of axons in the ICX

60. 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.

61. 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.

62. 2 major pathways for birdsong learning

63. Birdsong characteristics

64. 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]

65. 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.

66. 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 Learning Still an active area of research We know a little regarding song production in species when only males sing (*how is this studied?)

67. [Sexual dimorphism] Song System – 2 groups of nuclei: Motor – posterior forebrain: song production Feedback – anterior forebrain: oral learning Posterior pathway: - necessary for products of learned sounds. Higher visual center (HVC)  RA arhistriatum  hypoglossal nucleus: motor neurons centrally vocal 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)

68. Sexual dimorphism-song nuclei

69. Sexual Dimorphism
In Mammals:

70. 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).

72. 3. Imprinting Learning of cues through i. d
3. Imprinting Learning 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.

74. What happens if baby is in isolation during critical period
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 Path Auditory stem  nucleus of anti forebrain activated as in previous examples of selective elimination of inputs occurs during late critical period in response to experience.

75. Binocular Vision Ability 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.

76. Critical period for binocular vision development

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

78. 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’.