1. Development of Neural Circuits Lecture 4

2. Stages of Cellular Activity n 6 distinct stages 1. Neurogenesis 2. Cell migration 3. Differentiation 4. Synaptogenesis 5. Neuronal cell death 6. Synaptic rearrangement ~

3. Neurogenesis n Precursors (stem) cells l Neural tube’s ventricular zone l Induction signals n Asymmetrical mitosis l  another stem cell –Can divide again l  neuroblast –Cannot divide n Neuroblasts  neurons & glia ~

4. Neuronal Migration n Neural crest  PNS l Guided by cell adhesion molecules (CAMs) n Neural tube  CNS l along radial glia l later: along other neurons ~

5. Cell Migration n Long-distance migration l Along radial glia l Tangentially to other brain areas n Cerebellar neuroblasts l Mesoencephalon  l Rhombencephalon ~

6. Differentiation n Into specific neuron & glia types n Cell-autonomous l Genetic instructions n Cell-to-cell interactions l Induction signals l Critical periods ~

7. Construction of Circuits n Linkage of neurons in different regions l Growth of axon from origin to target l Formation of appropriate synapses n Cell-to-cell signaling l Tropic factors l Trophic factors ~

8. Axon Guidance n Axonal growth cone l Filopodia n Decision points l Decussate or not n Chemical cues l Ligands/receptors ~ n Non-diffusable cues l CAMs l Tropic & trophic n Diffusable chemical signals l Attraction netrins l Repulsion Semaphorins ~

9. Synaptogenesis n Superior cervical ganglion (PNS) l  eyes l  ear blood vessels n After axons reach target l Establish synapse l Retract & regrow l Do not form synapse ~

10. Synaptogenesis n Neurotropic factors l Ephrins & cadherins l Specificity  ligand/receptor types n Neurotrophic factors (neurotrophins) l After synapse formation l Cell-to-cell signals l Nerve growth factor (NGF) l  neurite growth ~

11. Apoptosis n Neuronal cell death l programmed cell death l 20-80% of neurons in a region l lack of neurotrophic factors n Wrong or no connection l neurons wither & die ~

12. Synaptic Rearrangement n Competition l elimination of synapses l formation of new synapses n Activity-dependent l Neurotransmitter release n Losing axon retracts l May strengthen synapse at other targets l Winner  synapses at target ~