Download BN04 Development of Neural Circuits

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