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 PNSGuided by cell adhesion molecules (CAMs)

Neural tube CNSalong radial glialater: 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 coneFilopodia

Decision pointsDecussate or not

Chemical cuesLigands/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 ~