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  1. 1. Nervous System Development
  2. 2. Overview <ul><li>The human nervous system begins to form at 3 weeks </li></ul><ul><li>Brain development continues throughout life. </li></ul><ul><ul><li>the same events that shape the brain during development are responsible for storing information throughout life. </li></ul></ul><ul><li>Critical periods occur throughout development </li></ul><ul><ul><li>periods when a neuron is in the process of becoming a specific type of neuron </li></ul></ul><ul><li>Neurons are generated at the rate of a quarter million per minute during development </li></ul><ul><li>The finished adult network contains 100 billion neurons which interact to produce movement, perception, emotion, etc. </li></ul>
  3. 3. The Beginning <ul><li>The neural plate starts to thicken at 3-4 weeks </li></ul><ul><ul><li>embryo is 1/10 inch long </li></ul></ul><ul><li>Parallel ridges form </li></ul><ul><li>Ridges fold in toward each other </li></ul><ul><li>  Fuse to form the neural tube </li></ul><ul><li>Top of tube thickens into 3 bulges: </li></ul><ul><ul><li>hindbrain, midbrain, forebrain </li></ul></ul>
  4. 4. Development of the Brain <ul><li>The rostral (front) part of the neural tubes goes on to develop into the brain and the rest of the neural tube develops into the spinal cord. </li></ul><ul><li>Neural crest cells become the peripheral nervous system. </li></ul><ul><li>At the front end of the neural tube, three major brain areas are formed: forebrain, midbrain and hindbrain. </li></ul><ul><li>By the 7th week of development, these areas divide again = encephalization. </li></ul>
  5. 5. Birth of Neurons <ul><li>Formed by interaction between 2 of the embryo’s 3 cell layers </li></ul><ul><li>Signals from one layer transform adjacent layer into neural tissue </li></ul><ul><li>This develops into the neural plate </li></ul><ul><li>Growth factors in the embryo act on the first cell layer, which causes formation of neural tissue </li></ul><ul><li>Various signals, some triggered by homeobox genes play a role in this process </li></ul>
  6. 6. Studying Neural Development <ul><li>Many initial steps in neural development are the same across species </li></ul><ul><li>Studies in roundworms, fruit flies, frogs, zebra fish, mouse, rat, chicken, cat, monkey </li></ul>
  7. 7. Steps in Neuron Development <ul><li>Cell proliferation </li></ul><ul><li>Cell migration </li></ul><ul><li>Cell differentiation </li></ul>
  8. 8. Cell Proliferation <ul><li>Neurons are initially produced in the neural tube </li></ul><ul><li>Migrate to a final destination in the brain </li></ul><ul><li>Collect together to form various structures </li></ul><ul><li>Neural circuits form </li></ul><ul><li>Improper or redundant connections are eliminated </li></ul>
  9. 9. Cell Fate <ul><li>As neurons are generated, the first cells become part of the deepest cortical layer </li></ul><ul><li>Cells formed later populate superficial areas </li></ul><ul><li>What determines neuron type? </li></ul><ul><ul><li>determined early in development </li></ul></ul><ul><li>Mother neurons generate young neurons that migrate from deep in the brain to predetermined points in the cortex </li></ul><ul><li>Alternate theory: all neurons are = before migration </li></ul><ul><ul><li>Area specific differences arise later </li></ul></ul><ul><ul><li>Later interactions determine where a neuron finally resides </li></ul></ul>
  10. 10. Neurotransmitter Determination <ul><li>Neurons grown in a petri dish without any other cell types produce norepinephrine </li></ul><ul><li>If the same neurons are cultured with other cells , they produce acetylcholine </li></ul><ul><li>The final determination of the substance a neuron produces is influenced by chemical factors in the environment </li></ul><ul><li>Signals from target cell </li></ul>
  11. 11. Cell Migration <ul><li>As neurons are produced, they move from the neural tube’s ventricular zone (inner surface) to the outer surface, near the border of the marginal zone </li></ul><ul><li>When neurons stop dividing, they form a layer between these 2 zones, the intermediate zone </li></ul><ul><li>This thickens as the developing brain </li></ul><ul><li>In some parts of the brain, a layer forms between the ventricular & intermediate zones , the subventricular zone </li></ul><ul><ul><li>Here cells continue to be produced </li></ul></ul><ul><li>Give rise to many neurons & glia that migrate to form the forebrain </li></ul>
  12. 12. Glial Cells Direct Migration <ul><li>Direct the movement of many neurons to their destination </li></ul><ul><li>Neurons hitch onto long glial fibers </li></ul><ul><li>Move monorail fashion to different areas of the developing mammalian brain </li></ul><ul><li>Neuron binding to a glial cell triggers changes in the glial cell that induce migration </li></ul><ul><li>Young neurons follow scaffolding of glial fibers of varying lengths & directions </li></ul>
  13. 13. Factors Effecting Movement <ul><li>Adhesion molecules bind neurons to glia </li></ul><ul><li>Play a key role in migration of neurons along glial fibers </li></ul>
  14. 14. Pathfinding Within Targets <ul><li>Once in final location, neurons must make proper connections </li></ul><ul><li>They do this through axons </li></ul><ul><li>Initially growth is genetically determined </li></ul><ul><li>Later influenced by chemical & mechanical cues </li></ul><ul><li>Axon growth is directed by enlargements at their tips, called growth cones </li></ul><ul><ul><li>Penetrate dense tissue ‘til reach destination </li></ul></ul>
  15. 15. Direction of Growth <ul><li>Direction of growth influenced by 3 factors: </li></ul><ul><li>Differences in texture and stickiness of tissue on which it grows </li></ul><ul><li>Molecular cues from cells it encounters </li></ul><ul><li>Scattered gradients of molecules produced by the target or other remote cells </li></ul><ul><li>In grasshoppers, guidepost cells trigger change in the direction of migration of the growth cone </li></ul>
  16. 16. Neural Cell Adhesion Molecules (NCAMs) <ul><li>Pathfinding is guided by special recognition molecules on both the growth cone & the target cell </li></ul><ul><ul><li>Neural Cell Adhesion Molecules (NCAMs) </li></ul></ul><ul><li>Related molecules play similar roles in pathway recognition in both vertebrates and invertebrates </li></ul><ul><li>Related molecules play similar role in vertebrates & invertebrates </li></ul>
  17. 17. Nerve Growth Factor <ul><li>A protein that directs the growth of axons </li></ul><ul><li>Orientation of axons is determined by gradients, or concentration changes of NGF </li></ul><ul><li>Suggests growth cones can sense & respond to gradients of chemical signals </li></ul>
  18. 18. Evidence for Importance of Gradients <ul><li>Using cells from chick brains, characterized a molecule that guides retinal axons </li></ul><ul><li>Likely to be involved in the formation of connections from the retina within the optic tectum </li></ul><ul><ul><li>part of chick brain that processes visual information </li></ul></ul>
  19. 19. Neuron Survival <ul><li>Twice as many neurons are generated as survive </li></ul><ul><li>Survival of a young neuron depends on interactions with the target neuron </li></ul><ul><li>Target cells secrete ‘survival molecules’ = tropic factors </li></ul><ul><li>Extent of activity among neural connections strengthens or weakens connections </li></ul>
  20. 20. Tropic Factors <ul><li>Neurons compete for survival chemicals called tropic factors , supplied by the target </li></ul><ul><li>Include: </li></ul><ul><ul><li>NGF </li></ul></ul><ul><ul><li>Brain-derived neurotropic factor </li></ul></ul><ul><ul><li>Neurotropin 3 </li></ul></ul><ul><ul><li>Ciliary neurotropc factor </li></ul></ul><ul><li>Each supports survival of a distinct group of neurons </li></ul>
  21. 21. Formation of Synapses <ul><li>Involves complex interactions between the neuron and its target </li></ul><ul><li>The neuron may play a role in organizing the membrane of the target cell to ensure good connection </li></ul><ul><li>The neuron regulates the number and distribution of receptors </li></ul>
  22. 22. Critical Periods <ul><li>Brain cells prune away incorrect connections </li></ul><ul><li>This occurs during critical periods </li></ul><ul><li>The brain’s precise wiring is not in place at birth </li></ul><ul><li>Organism’s interaction with the environment fine tunes connections </li></ul><ul><li>After the critical period connections are less likely to change </li></ul>
  23. 23. Demonstrating Critical Periods <ul><li>If a monkey is raised from birth to 6 mos. with one eyelid sewn shut, it permanently loses vision in the shut eye </li></ul><ul><li>Loss of vision is caused by interruption of necessary stages of development of special structures in the visual cortex </li></ul><ul><li>Critical periods exist throughout development </li></ul><ul><ul><li>Capabilities for language, music, or math must develop before puberty </li></ul></ul><ul><ul><li>Injury or social deprivation at a critical stage may affect perceptual or personality development </li></ul></ul>
  24. 24. Unanswered Questions <ul><li>How do many cell types arise from one population? </li></ul><ul><li>What controls the number of neurons? </li></ul><ul><li>How do neurons find their targets? </li></ul><ul><li>How does experience effect development? </li></ul><ul><li>How do contacts form & become functional circuits? </li></ul>
  25. 25. The Developing Brain
  26. 26. Fetal Brain Growth
  27. 27. Infant & Adult Human Brains