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Development of Neural Circuits

This lesson explores the six critical stages of cellular activity involved in neural circuit development: Neurogenesis, Cell Migration, Differentiation, Synaptogenesis, Neuronal Cell Death, and Synaptic Rearrangement. We delve into the processes of neurogenesis, from stem cell division to neuroblast differentiation, and discuss cell migration in both the peripheral and central nervous systems. Additionally, we analyze synaptogenesis involving neurotropic factors, the role of apoptosis in neuronal death, and the importance of synaptic rearrangement for circuit efficiency. Understanding these stages provides insights into neural development and function.

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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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