Early Experience and Developmental Learning

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

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 Psychobiology43: 71-81. 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 • http://web.uvic.ca/psyc/coursematerial/psyc435a.f01/435A/Week%202%20Lecture%20Notes.pdf

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: • http://www.pitc.org/

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. 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. 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.