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Development of Neural Circuits

Development of Neural Circuits. Lesson 5. Stages of Cellular Activity. 6 distinct stages 1. Neurogenesis 2. Cell migration 3. Differentiation 4. Synaptogenesis 5. Neuronal cell death 6. Synaptic rearrangement ~. Neurogenesis. Precursors (stem) cells Neural plate & tube stages

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Development of Neural Circuits

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  1. Development of Neural Circuits Lesson 5

  2. Stages of Cellular Activity • 6 distinct stages 1. Neurogenesis 2. Cell migration 3. Differentiation 4. Synaptogenesis 5. Neuronal cell death 6. Synaptic rearrangement ~

  3. Neurogenesis • Precursors (stem) cells • Neural plate & tube stages • Neural tube’s ventricular zone • Induction signals ~

  4. Symmetrical Mitosis • Results in 2 stem cells • Slow & unlimited division • Mediated by notch protein • Required for self-renewal • Stem & progenitor cells ~

  5. Asymmetrical Mitosis • Results in neuroblast + progenitor • Neuroblasts • Differentiate into neurons & glia • Progenitors: • rapid, but limited division • Mediated by numb protein • Asymmetrically distributed in mitosis • Inhibits notch protein ~

  6. Neuronal Migration: PNS • Neural crest  PNS • Initial position anterior-posterior factor • Epithelial  mesenchymal transition • Snail1 & 2   adhesion molecules • Guided by • cell adhesion molecules (CAMs) • Secreted peptide hormones • Along musculoskeletal tissues ~

  7. Neuronal Migration: CNS • Neural tube  CNS • Primarily along radial glia • Some along axons • CAMs ~

  8. Cell Migration • Long-distance migration • Along radial glia • Tangentially to other brain areas • Cerebellar neuroblasts • Mesoencephalon  • Rhombencephalon ~

  9. Cell Differentiation • Stem cells  neurons & glia • Many types of each • Cell-to-cell signaling • Particularly young precursor cells • BMPs, shh, Wnt induction signals • Cell autonomous • Transcription regulation • bHLH proneural genes  neurons • Inhibit bHLH  glia ~

  10. Construction of Circuits • Linkage of neurons in different regions • Growth of axon from origin to target • Formation of appropriate synapses • Cell-to-cell signaling • Tropic factors • Trophic factors ~

  11. Axon Guidance • Axonal growth cone • Filopodia • Decision points • Decussate or not • Chemical cues • Ligands/receptors ~ • Non-diffusable cues • CAMs • Tropic & trophic • Diffusable chemical signals • Attraction • netrins • Repulsion • Semaphorins ~

  12. Synaptogenesis • Superior cervical ganglion (PNS) •  eyes •  ear blood vessels • After axons reach target • Establish synapse • Retract & regrow • Do not form synapse ~

  13. Synaptogenesis • Neurotropic factors • Ephrins & cadherins • Specificity  ligand/receptor types • Neurotrophic factors (neurotrophins) • After synapse formation • Cell-to-cell signals • Nerve growth factor (NGF) •  neurite growth ~

  14. Apoptosis • Neuronal cell death • programmed cell death • 20-80% of neurons in a region • lack of neurotrophic factors • Wrong or no connection • neurons wither & die ~

  15. Synaptic Rearrangement • Competition • elimination of synapses • formation of new synapses • Activity-dependent • Neurotransmitter release • Losing axon retracts • May strengthen synapse at other targets • Winner  synapses at target ~

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