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

Induction signals
 Asymmetrical mitosis

 another stem cell
– Can divide again

 neuroblast
– Cannot divide
 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 ~
 Axon Guidance
 Axonal growth cone  Non-diffusable cues

Filopodia 
CAMs
 Decision points 
Tropic & trophic

Decussate or not  Diffusable chemical
 Chemical cues signals

Ligands/receptors ~

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 ~