Pinel basics ch07


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Pinel basics ch07

  1. 1. Chapter 7 Development of the Nervous System From Fertilized Egg to You <ul><li>This multimedia product and its contents are protected under copyright law. The following are prohibited by law: </li></ul><ul><li>any public performance or display, including transmission of any image over a network; </li></ul><ul><li>preparation of any derivative work, including the extraction, in whole or in part, of any images; </li></ul><ul><li>any rental, lease, or lending of the program. </li></ul>
  2. 2. Neurodevelopment <ul><li>Neural development – an ongoing process, the nervous system is plastic </li></ul><ul><li>Complex </li></ul><ul><li>Experience plays a key role </li></ul><ul><li>Dire consequences when something goes wrong </li></ul>
  3. 3. The Case of Genie <ul><li>What impact does severe deprivation have on development? </li></ul><ul><li>At age 13, Genie weighed 62 pounds and could not chew solid food </li></ul><ul><li>Beaten, starved, restrained, kept in a dark room, denied normal human interactions </li></ul><ul><li>Can the damage be undone? </li></ul>
  4. 4. The Case of Genie <ul><li>Genie’s story is often cited for what it told us about language development (she only uses short utterances), but it also illustrates the impact of abuse on all aspects of behavior </li></ul><ul><ul><li>No response to temperature extremes </li></ul></ul><ul><ul><li>Unable to chew </li></ul></ul><ul><ul><li>Extremely inappropriate reactions (‘silent tantrums’) </li></ul></ul><ul><ul><li>Easily terrified </li></ul></ul><ul><li>How can neurodevelopment explain this? </li></ul>
  5. 5. Phases of Development <ul><li>Ovum + sperm = zygote </li></ul><ul><li>Cells then multiply and </li></ul><ul><ul><li>Differentiate </li></ul></ul><ul><ul><li>Move and take their appropriate positions </li></ul></ul><ul><ul><li>Make the needed functional relations with other cells </li></ul></ul><ul><li>Developing neurons accomplish these things in 5 phases </li></ul>
  6. 6. Induction of the Neural Plate <ul><li>A patch of tissue on the dorsal surface of the embryo </li></ul><ul><li>Development induced by chemical signals from the mesoderm (the “organizer”) </li></ul><ul><li>Visible 3 weeks after conception </li></ul><ul><li>3 layers of embryonic cells </li></ul><ul><ul><li>Ectoderm – outermost, mesoderm – middle, endoderm - innermost </li></ul></ul>
  7. 7. Induction of the Neural Plate <ul><li>Part of induction is inhibition of bone morphogenetic proteins that suppress neurodevelopment </li></ul><ul><li>Totipotent – earliest cells have the ability to become any type of body cell </li></ul><ul><li>With the development of the neural plate cell destinies become specified – cells are multipotent – able to develop into any type of mature nervous system cell </li></ul>
  8. 8. Stem cells <ul><li>Neural plate cells are often referred to as stem cells. Stem cells: </li></ul><ul><ul><li>seem to have an unlimited capacity for self-renewal </li></ul></ul><ul><ul><li>can develop into different mature cell types (totipotent) </li></ul></ul><ul><li>As the neural tube develops specificity increases, resulting in glial and neural stem cells (multipotent) </li></ul>
  9. 10. Neural Proliferation <ul><li>Neural plate folds to form the neural groove which then fuses to form the neural tube </li></ul><ul><li>Inside will be the cerebral ventricles and neural tube </li></ul><ul><li>Neural tube cells proliferate in species-specific ways – 3 swellings at the anterior end in humans will become the forebrain, midbrain, and hindbrain </li></ul>
  10. 11. Migration <ul><li>Once cells have been created through cell division in the ventricular zone of the neural tube they migrate </li></ul><ul><li>Migrating cells are immature, lacking axons and dendrites </li></ul><ul><li>Radial migration – towards the outer wall of the tube </li></ul><ul><li>Tangential migration – at a right angle to radial migration, parallel to the tube walls </li></ul><ul><li>Most cells engage in both types of migration </li></ul>
  11. 12. Migration <ul><li>Two types of neural tube migration </li></ul><ul><ul><li>Radial migration – moving out – usually by moving along radial glial cells </li></ul></ul><ul><ul><li>Tangential migration – moving up </li></ul></ul><ul><li>Two methods of migration </li></ul><ul><ul><li>Somal – an extension develops that leads migration, cell body follows </li></ul></ul><ul><ul><li>Glial-mediated migration – cell moves along a radial glial network </li></ul></ul>
  12. 15. Aggregation <ul><li>the process of cells that are done migrating aligning themselves with others cells and forming structures. </li></ul><ul><li>Cell-adhesion molecules (CAMs) – aid both migration and aggregation </li></ul><ul><li>CAMs found on cell surfaces, recognize and adhere to molecules </li></ul>
  13. 16. Axon Growth and Synapse Formation <ul><li>Once migration is complete and structures have formed (aggregation), axons and dendrites begin to grow </li></ul><ul><li>Growth cone – at the growing tip of each extension, extends and retracts filopidia as if finding its way </li></ul><ul><li>Chemoaffinity hypothesis – postsynaptic targets release a chemical that guides axonal growth – but this does not explain the often circuitous routes often observed </li></ul>
  14. 17. Axon growth <ul><li>Mechanisms underlying axonal growth are the same across species </li></ul><ul><li>A series of chemical signals exist along the way </li></ul><ul><li>Such guidance molecules are often released by glia </li></ul><ul><ul><li>chemoattractants attract growing axons </li></ul></ul><ul><ul><li>chemorepellants repel them </li></ul></ul><ul><li>Adjacent growing axons also provide signals </li></ul>
  15. 18. Axon growth <ul><li>Pioneer growth cones – the 1 st to travel a route – follow guidance molecules </li></ul><ul><li>Fasciculation – the tendency of developing axons to grow along the paths established by preceding axons </li></ul><ul><li>Topographic gradient hypothesis – seeks to explain topographic maps </li></ul>
  16. 19. Synaptogenesis <ul><li>Formation of new synapses </li></ul><ul><li>Depends on the presence of glial cells – especially astrocytes </li></ul><ul><li>High levels of cholesterol are needed – supplied by astrocytes </li></ul><ul><li>Chemical signal exchange between pre and postsynaptic neurons is needed </li></ul><ul><li>A variety of signals act on developing neurons </li></ul>
  17. 20. Neuron Death and Synapse Rearrangement <ul><li>~50% more neurons than are needed are produced – death is normal </li></ul><ul><li>Neurons die due to failure to compete for chemicals provided by targets </li></ul><ul><ul><li>Increase targets > decreased death </li></ul></ul><ul><ul><li>Destroy some cells > increased survival of remaining cells </li></ul></ul><ul><ul><li>Increase number of innervating axons > decreased proportion survive </li></ul></ul>
  18. 21. Life-preserving chemicals <ul><li>Neurotrophins – promote growth and survival, guide axons, stimulate synaptogenesis </li></ul><ul><ul><li>Nerve growth factor (NGF) </li></ul></ul><ul><li>Both passive cell death (necrosis) and active cell death (apoptosis) </li></ul><ul><li>Apoptosis is safer than necrosis – “cleaner” </li></ul>
  19. 22. Postnatal Cerebral Development in Human Infants <ul><li>Postnatal growth is a consequence of </li></ul><ul><ul><li>Synaptogenesis </li></ul></ul><ul><ul><li>Myelination – sensory areas and then motor areas. Myelination of prefrontal cortex continues into adolescence </li></ul></ul><ul><ul><li>Increased dendritic branches </li></ul></ul><ul><li>Overproduction of synapses may underlie the greater plasticity of the young brain </li></ul>
  20. 23. Development of the Prefrontal Cortex <ul><li>Believed to underlie age-related changes in cognitive function </li></ul><ul><li>No single theory explains the function of this area </li></ul><ul><li>Prefrontal cortex plays a role in working memory, planning and carrying out sequences of actions, and inhibiting inappropriate responses </li></ul>
  21. 25. Effects of Experience on Neural Circuits <ul><li>Neurons and synapses that are not activated by experience usually do not survive – “use it or lose it” </li></ul><ul><li>Humans are uniquely slow in neurodevelopment – allows for fine-tuning </li></ul><ul><li>How do nature and nurture interact to modify the early development, maintenance, and reorganization of neural circuits? </li></ul>
  22. 26. Early Studies of Experience and Neurodevelopment <ul><li>Early visual deprivation: </li></ul><ul><ul><li>fewer synapses and dendritic spines in 1° visual cortex </li></ul></ul><ul><ul><li>deficits in depth and pattern vision </li></ul></ul><ul><li>Enriched environment: </li></ul><ul><ul><li>thicker cortices </li></ul></ul><ul><ul><li>greater dendritic development </li></ul></ul><ul><ul><li>more synapses per neuron </li></ul></ul>
  23. 27. Competitive Nature of Experience and Neurodevelopment <ul><li>Monocular deprivation changes the pattern of synaptic input into layer IV of V1 </li></ul><ul><li>Altered exposure during a sensitive period leads to reorganization </li></ul><ul><li>Active motor neurons take precedence over inactive ones </li></ul>
  24. 28. Effects of Experience on Topographic Sensory Cortex Maps <ul><li>Cross-modal (involving at least 2 different senses) rewiring experiments demonstrate sensory cortex plasticity – with visual input, auditory cortex can see </li></ul><ul><li>Change input, change cortical topography - shifted auditory map in prism-exposed owls </li></ul>
  25. 29. Effects of Experience on Topographic Sensory Cortex Maps <ul><li>Neural activity prior to sensory input plays a role in development – ferret visual development disrupted by interference with neuronal activity prior to eye opening </li></ul><ul><li>Early music training influences the organization of human auditory cortex – f MRI studies </li></ul>
  26. 30. Neuroplasticity in Adults <ul><li>Mature brain changes and adapts </li></ul><ul><li>Neurogenesis (growth of new neurons) seen in olfactory bulbs and hippocampi of adult mammals </li></ul><ul><li>Researchers still looking to see if there is neurogenesis in other adult brain structures </li></ul>
  27. 31. Effects of Experience on the Reorganization of the Adult Cortex <ul><li>Tinnitus (ringing in the ears) – produces major reorganization of 1° auditory cortex </li></ul><ul><li>Adult musicians who play instruments fingered by hand have an enlarged representation of the hand in right somatosensory cortex </li></ul><ul><li>Skill training leads to reorganization of motor cortex </li></ul>
  28. 32. Autism <ul><li>4 of every 10,000 individuals – 3 core symptoms: </li></ul><ul><ul><li>Reduced ability to interpret emotions and intentions </li></ul></ul><ul><ul><li>Reduced capacity for social interaction </li></ul></ul><ul><ul><li>Preoccupation with a single subject or activity </li></ul></ul><ul><li>Intensive behavioral therapy may improve function </li></ul><ul><li>Heterogenous – level of brain damage and dysfunction varies </li></ul>
  29. 33. Autism <ul><li>Most have some abilities preserved – rote memory, ability to complete jigsaw puzzles, musical ability, artistic ability </li></ul><ul><li>Savants – intellectually handicapped individuals who display specific cognitive or artistic abilities </li></ul><ul><li>~1/10 autistic individuals display savant abilities </li></ul><ul><li>Perhaps a consequence of compensatory functional improvement in the right hemisphere following damage to the left </li></ul>
  30. 34. Neural Basis of Autism <ul><li>Genetic basis </li></ul><ul><ul><li>Siblings of the autistic have a 5% chance of being autistic </li></ul></ul><ul><ul><li>60% concordance rate for monozygotic twins </li></ul></ul><ul><li>Several genes interacting with the environment </li></ul><ul><li>Brain damage tends to be widespread, but is most commonly seen in the cerebellum </li></ul>
  31. 35. Neural Basis for Autism <ul><li>Thalidomide – given early in pregnancy – increases chance of autism </li></ul><ul><ul><li>Indicates neurodevelopmental error occurs within 1 st few weeks of pregnancy when motor neurons of the cranial nerves are developing </li></ul></ul><ul><ul><li>Consistent with observed deficits in face, mouth, and eye control </li></ul></ul><ul><li>Anomalies in ear structure indicate damage occurs between 20 and 24 days after conception </li></ul><ul><li>Evidence for a role of a gene on chromosome 7 </li></ul>
  32. 37. Williams Syndrome <ul><li>~ 1 of every 20,000 births </li></ul><ul><li>Mental retardation and an uneven pattern of abilities and disabilities </li></ul><ul><li>Sociable, empathetic, and talkative – exhibit language skills, music skills and an enhanced ability to recognize faces </li></ul><ul><li>Profound impairments in spatial cognition </li></ul><ul><li>Usually have heart disorders associated with a mutation in a gene on chromosome 7 – the gene (and others) are absent in 95% of those with Williams </li></ul>
  33. 38. Williams Syndrome <ul><li>Variety of abilities – like autistics </li></ul><ul><li>Evidence for a role of chromosome 7 – as in autism </li></ul><ul><li>Underdeveloped occipital and parietal cortex, normal frontal and temporal </li></ul><ul><li>“ elfin” appearance – short, small upturned noses, oval ears, broad mouths </li></ul>
  34. 39. Think About It <ul><li>Compare and contrast autism and Williams syndrome </li></ul><ul><li>What do these disorders demonstrated about neurodevelopment? </li></ul><ul><li>How are such developmental disorders studied? </li></ul>