1. Copyright © 2009 Allyn & Bacon From Fertilized Egg to You This multimedia product and its contents are protected under copyright law. The following are prohibited by law: any public performance or display, including transmission of any image over a network; preparation of any derivative work, including the extraction, in whole or in part, of any images; any rental, lease, or lending of the program. Chapter 9 Development of the Nervous System

2. Copyright © 2009 Allyn & Bacon Neurodevelopment Neural development – an ongoing process; the nervous system is plastic A complex process Experience plays a key role Dire consequences when something goes wrong

3. Copyright © 2009 Allyn & Bacon The Case of Genie What impact does severe deprivation have on development? At age 13, Genie weighed 62 pounds and could not chew solid food Beaten, starved, restrained, kept in a dark room, denied normal human interactions Can the damage be undone?

4. Copyright © 2009 Allyn & Bacon The Case of Genie (continued) Genie’s story is often cited for what it tells us about language development (she only uses short utterances), but it also illustrates the impact of abuse on all aspects of behavior No response to temperature extremes Unable to chew Extremely inappropriate reactions (“silent tantrums”) Easily terrified How can neurodevelopment explain this?

5. Copyright © 2009 Allyn & Bacon Phases of Development Ovum + sperm = zygote Developing neurons accomplish these things in five phases Induction of the neural plate Neural proliferation Migration and aggregation Axon growth and synapse formation Neuron death and synapse rearrangement

6. Copyright © 2009 Allyn & Bacon Induction of the Neural Plate A patch of tissue on the dorsal surface of the embryo becomes the neural plate Development induced by chemical signals from the mesoderm (the “organizer”) Visible three weeks after conception Three layers of embryonic cells Ectoderm (outermost) Mesoderm (middle) Endoderm (innermost)

7. Copyright © 2009 Allyn & Bacon Induction of the Neural Plate (continued) Neural plate cells are often referred to as embryonic stem cells Have unlimited capacity for self renewal Can become any kind of mature cell Totipotent – earliest cells have the ability to become any type of body cell Multipotent – with development, neural plate cells are limited to becoming one of the range of mature nervous system cells

8. Copyright © 2009 Allyn & Bacon How the neural plate develops into the neural tube during the third and fourth weeks of human embryological development Induction of the Neural Plate (continued)

9. Copyright © 2009 Allyn & Bacon Neural Proliferation Neural plate folds to form the neural groove, which then fuses to form the neural tube Inside will be the cerebral ventricles and neural tube Neural tube cells proliferate in species-specific ways: three swellings at the anterior end in humans will become the forebrain, midbrain, and hindbrain Proliferation is chemically guided by the organizer areas – the roof plate and the floor plate

10. Copyright © 2009 Allyn & Bacon Migration Once cells have been created through cell division in the ventricular zone of the neural tube, they migrate Migrating cells are immature, lacking axons and dendrites

11. Copyright © 2009 Allyn & Bacon Migration (continued) Two types of neural tube migration Radial migration (moving out) – usually by moving along radial glial cells Tangential migration (moving up) Two methods of migration Somal – an extension develops that leads migration, cell body follows Glial-mediated migration – cell moves along a radial glial network Most cells engage in both types of migration

12. Copyright © 2009 Allyn & Bacon Migration (continued) Two types of neural migration: radial migration and tangential migration

13. Copyright © 2009 Allyn & Bacon Migration (continued) Somal translocation and glia-mediated migration

14. Copyright © 2009 Allyn & Bacon Neural Crest A structure dorsal to the neural tube and formed from neural tube cells Develops into the cells of the peripheral nervous system Cells migrate long distances

15. Copyright © 2009 Allyn & Bacon Aggregation After migration, cells align themselves with others cells and form structures Cell-adhesion molecules (CAMs) Aid both migration and aggregation CAMs recognize and adhere to molecules Gap junctions pass cytoplasm between cells Prevalent in brain development May play a role in aggregation and other processes

16. Copyright © 2009 Allyn & Bacon Axon Growth and Synapse Formation Once migration is complete and structures have formed (aggregation), axons and dendrites begin to grow Growth cone – at the growing tip of each extension, extends and retracts filopodia as if finding its way Chemoaffinity hypothesis – postsynaptic targets release a chemical that guides axonal growth, but this does not explain the often circuitous routes often observed

17. Copyright © 2009 Allyn & Bacon Axon Growth Mechanisms underlying axonal growth are the same across species A series of chemical signals exist along the way – attracting and repelling Such guidance molecules are often released by glia Adjacent growing axons also provide signals

18. Copyright © 2009 Allyn & Bacon Axon Growth (continued) Pioneer growth cones – the first to travel a route, interact with guidance molecules Fasciculation – the tendency of developing axons to grow along the paths established by preceding axons Topographic gradient hypothesis – seeks to explain topographic maps

19. Copyright © 2009 Allyn & Bacon Synaptogenesis Formation of new synapses Depends on the presence of glial cells – especially astrocytes High levels of cholesterol are needed – supplied by astrocytes Chemical signal exchange between pre- and postsynaptic neurons is needed A variety of signals act on developing neurons

20. Copyright © 2009 Allyn & Bacon Neuron Death and Synapse Rearrangement ~50% more neurons than are needed are produced – death is normal Neurons die due to failure to compete for chemicals provided by targets The more targets, the fewer cell deaths Destroying some cells increases survival rate of remaining cells Increasing number of innervating axons decreases the proportion that survives

21. Copyright © 2009 Allyn & Bacon Life-Preserving Chemicals Neurotrophins – promote growth and survival, guide axons, stimulate synaptogenesis Nerve growth factor (NGF) Both passive cell death (necrosis) and active cell death (apoptosis) Apoptosis is safer than necrosis – “cleaner”

22. Copyright © 2009 Allyn & Bacon Postnatal Cerebral Development in Human Infants Postnatal growth is a consequence of Synaptogenesis Myelination – sensory areas and then motor areas. Myelination of prefrontal cortex continues into adolescence Increased dendritic branches Overproduction of synapses may underlie the greater plasticity of the young brain

23. Copyright © 2009 Allyn & Bacon Development of the Prefrontal Cortex Believed to underlie age-related changes in cognitive function No single theory explains the function of this area Prefrontal cortex plays a role in working memory, planning and carrying out sequences of actions, and inhibiting inappropriate responses

24. Copyright © 2009 Allyn & Bacon Effects of Experience on Neural Circuits Neurons and synapses that are not activated by experience usually do not survive – use it or lose it Humans are uniquely slow in neurodevelopment – allows for fine-tuning How do nature and nurture interact to modify the early development, maintenance, and reorganization of neural circuits?

25. Copyright © 2009 Allyn & Bacon Early Studies of Experience and Neurodevelopment Early visual deprivation Fewer synapses and dendritic spines in primary visual cortex Deficits in depth and pattern vision Enriched environment Thicker cortexes Greater dendritic development More synapses per neuron

26. Copyright © 2009 Allyn & Bacon Competitive Nature of Experi- ence and Neurodevelopment Monocular deprivation changes the pattern of synaptic input into layer IV of V1 (but not binocular deprivation) Altered exposure during a sensitive period leads to reorganization Active motor neurons take precedence over inactive ones

27. Copyright © 2009 Allyn & Bacon How Experience Might Influence Neurodevelopment Many possibilities Neural activity regulates the expression of genes that direct the synthesis of CAMs Neural activity influences the release of neurotrophins Some neural circuits are spontaneously active and this activity is needed for normal development

28. Copyright © 2009 Allyn & Bacon Neuroplasticity in Adults Mature brain changes and adapts Neurogenesis (growth of new neurons) seen in olfactory bulbs and hippocampuses of adult mammals – adult neural stem cells created in the ependymal layer lining in ventricles and adjacent tissues

29. Copyright © 2009 Allyn & Bacon Effects of Experience on Adult Cortex Reorganization Tinnitus (ringing in the ears) – produces major reorganization of primary auditory cortex Adult musicians who play instruments fingered by left hand have an enlarged representation of the hand in the right somatosensory cortex Skill training leads to reorganization of motor cortex

30. Copyright © 2009 Allyn & Bacon Autism Three core symptoms Reduced ability to interpret emotions and intentions Reduced capacity for social interaction Preoccupation with a single subject or activity Intensive behavioral therapy may improve function Heterogenous – level of brain damage and dysfunction varies

31. Copyright © 2009 Allyn & Bacon Autism (continued) Incidence: 6.6 per 1,000 births (or 1 in 166) 80% males, 60% mentally retarded, 35% epileptic, 25% have little or no language ability Most have some abilities preserved – rote memory, jigsaw puzzles, musical ability, artistic ability Savants – intellectually handicapped individuals who display specific cognitive or artistic abilities ~1/10 autistic individuals display savant abilities Perhaps a consequence of compensatory functional improvement in one area following damage to another

32. Copyright © 2009 Allyn & Bacon Genetic Basis of Autism Siblings of the autistic have a 5% chance of being autistic 60% concordance rate for monozygotic twins Several genes interacting with the environment Thalidomide – given early in pregnancy – increases chance of autism Indicates neurodevelopmental error in first weeks of pregnancy as cranial nerve motor neurons develop Consistent with deficits in control of face, mouth, eye movements, and with abnormal ear structure Evidence for a role of a gene on chromosome 7

33. Copyright © 2009 Allyn & Bacon Neural Mechanisms of Autism Widespread damage, especially to cerebellum and associated brain stem structures Two lines of research Abnormal response to faces in autistic patients Spend less time than non-autistic subjects looking at faces, especially eyes Low fMRI activity in fusiform face area Possibly deficient in mirror neuron function

34. Copyright © 2009 Allyn & Bacon Williams Syndrome ~1 in every 20,000 births Mental retardation and an uneven pattern of abilities and disabilities Sociable, empathetic, and talkative – exhibit language skills, music skills, and an enhanced ability to recognize faces Profound impairments in spatial cognition Usually have heart disorders associated with a mutation in a gene on chromosome 7 – the gene (and others) is absent in 95% of those with Williams

35. Copyright © 2009 Allyn & Bacon Williams Syndrome (continued) Evidence for a role of chromosome 7 (as in autism) General thinning of cortex at juncture of occipital and parietal lobes, and at the orbitofrontal cortex “Elfin” appearance – short, small upturned noses, oval ears, broad mouths

36. Copyright © 2009 Allyn & Bacon cells differentiate together contracting Rat Heart