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Development of Neural Circuits. Lecture 4. 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 tube’s ventricular zone

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stages of cellular activity
Stages of Cellular Activity
  • 6 distinct stages

1. Neurogenesis

2. Cell migration

3. Differentiation

4. Synaptogenesis

5. Neuronal cell death

6. Synaptic rearrangement ~

neurogenesis
Neurogenesis
  • Precursors (stem) cells
    • Neural tube’s ventricular zone
    • Induction signals
  • Asymmetrical mitosis
    •  another stem cell
        • Can divide again
    •  neuroblast
        • Cannot divide
  • Neuroblasts  neurons & glia ~
neuronal migration
Neuronal Migration
  • Neural crest  PNS
    • Guided by cell adhesion molecules (CAMs)
  • Neural tube  CNS
    • along radial glia
    • later: along other neurons ~
cell migration
Cell Migration
  • Long-distance migration
    • Along radial glia
    • Tangentially to other brain areas
  • Cerebellar neuroblasts
    • Mesoencephalon 
    • Rhombencephalon ~
differentiation
Differentiation
  • Into specific neuron & glia types
  • Cell-autonomous
    • Genetic instructions
  • Cell-to-cell interactions
    • Induction signals
    • Critical periods ~
construction of circuits
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 ~
axon guidance
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 ~
synaptogenesis
Synaptogenesis
  • Superior cervical ganglion (PNS)
    •  eyes
    •  ear blood vessels
  • After axons reach target
    • Establish synapse
    • Retract & regrow
    • Do not form synapse ~
synaptogenesis1
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 ~
apoptosis
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 ~
synaptic rearrangement
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 ~