Development of Neural Circuits Lecture 4 Stages of

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Development of Neural Circuits Lecture 4

Development of Neural Circuits Lecture 4

Stages of Cellular Activity 6 distinct stages 1. Neurogenesis 2. Cell migration 3. Differentiation

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

Neurogenesis Precursors (stem) cells l Neural tube’s ventricular zone l Induction signals n Asymmetrical

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

Neuronal Migration Neural crest PNS l. Guided by cell adhesion molecules (CAMs) n Neural

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

Cell Migration Long-distance migration l Along radial glia l Tangentially to other brain areas

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

Differentiation Into specific neuron & glia types n Cell-autonomous l Genetic instructions n Cell-to-cell

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

Construction of Circuits Linkage of neurons in different regions l Growth of axon from

Construction of Circuits 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 ~ n

Axon Guidance n n n Axonal growth cone l. Filopodia Decision points l. Decussate

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

Synaptogenesis Superior cervical ganglion (PNS) l eyes l ear blood vessels n After axons

Synaptogenesis 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 ~ n

Synaptogenesis Neurotropic factors l Ephrins & cadherins l Specificity ligand/receptor types n Neurotrophic factors

Synaptogenesis 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 ~ n

Apoptosis Neuronal cell death l programmed cell death l 20 -80% of neurons in

Apoptosis 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 ~ n

Synaptic Rearrangement Competition l elimination of synapses l formation of new synapses n Activity-dependent

Synaptic Rearrangement 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 ~ n