Development of Neural Circuits

Lesson 5

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 plate & tube stages Neural tube’s ventricular zone Induction signals ~

Symmetrical Mitosis

Results in 2 stem cells Slow & unlimited division

Mediated by notch protein Required for self-renewal Stem & progenitor cells ~

Asymmetrical Mitosis Results in neuroblast + progenitor Neuroblasts

Differentiate into neurons & glia Progenitors:

rapid, but limited division Mediated by numb protein

Asymmetrically distributed in mitosis Inhibits notch protein ~

Neuronal Migration: PNS Neural crest PNS

Initial position anterior-posterior factor Epithelial mesenchymal transition

Snail1 & 2 adhesion molecules Guided by

cell adhesion molecules (CAMs) Secreted peptide hormones Along musculoskeletal tissues ~

Neuronal Migration: CNS

Neural tube CNSPrimarily along radial gliaSome along axons CAMs ~

Cell Migration

Long-distance migration Along radial glia Tangentially to other

brain areas Cerebellar neuroblasts

Mesoencephalon Rhombencephalon ~

Cell Differentiation Stem cells neurons & glia

Many types of each Cell-to-cell signaling

Particularly young precursor cells BMPs, shh, Wnt induction signals

Cell autonomous Transcription regulation bHLH proneural genes neurons Inhibit bHLH glia ~

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 ~