Synapse Formation

steps in CNS synapse formation

1. Pre- & post-synaptic priming. 2. Process: adhesion w/variety of adhesive molecules 3. bi-directional signaling 4. synaptic activity 5. stabilization of synapse

Why is the NMJ a good model?

1. large synapses 2. all synapses use ACh 3. function easy to test

7 steps in synapse formation

1. priming of presynaptic & postsynaptic terminals 2. initial contact 3. synapse formation & elimination 4. bidirectional signaling 5. synaptic activity 6. stabilization/refinement of synapse 7. excitatory/inhibitory balance

functions of Neurexin - Neuroligin

1. target recognition 2. adhesion 3. stabilize synapse 4. specialization / segregation of synapse types

latrotoxin

Neurexin agonist

Neuroligin synapse differentiation

Neuroligin-1: excitatory synapses Neuroligin-2: inhibitory synapses

Neuregulin: 1. location 2. function

1. NMJ presynaptic motor neuron & Schwann cell 2. stimulates local upregulation of ACh production in nearby muscle cell nucleus -> elimination of non-upregulated synapses

autism: 1. location 2. molecules involved

1. CNS 2. Neuroligin defect

steps in NMJ synapse formation

1. Growth cone approaches motor fiber. 2. Growth cone contacts fiber & terminal flattens. 3. Extracellular matrix/basal lamina accumulates at site of synapse. 4. Synaptic vesicles gather at terminal(s). 5. Mature NMJ forms w/ 1 terminal, matrix in synaptic cleft & folding of postsynaptic membrane.

6 sets of adhesive molecules: presynaptic - postsynaptic

1. N-CAM - N-CAM 2. Neurexin - Neuroligin 3. Ephrin - Eph 4. Cadherin - Cadherin 5. Integrin - Syndecan 6. Sidekick - Sidekick

myasthenia gravis: 1. location 2. molecules involved

1. NMJ 2. antibodies to AChR (90%); MuSK & Lrp4 (10%)

MuSK: 1. location 2. function 3. results of deficit

1. NMJ muscle cell 2. receptor for Agrin; co-receptor with Lrp4 -> initiates clustering of AChR at end-plate & stabilizes synapses w/Agrin 3. 'wandering' synapses; no postsynaptic AChR clusters

Lrp4: 1. location 2. function 3. results of deficit

1. NMJ muscle cell 2. receptor for Agrin; co-receptor with MuSK 3. 'wandering' synapses; no postsynaptic AChR clusters

Erb2: 1. location 2. function

1. NMJ muscle cell 2. receptor for Neuregulin

Agrin: 1. location 2. function 3. results of deficit

1. NMJ presynaptic motor neuron 2. promotes synapse stabilization by increasing MuSK receptor activity -> enlarges AChR clusters 3. 'wandering' synapses; decrease in postsynaptic AChr clusters

mechanism of NMJ synapse elimination

ACh degrades 'unprotected' terminals not contacted by an axon

2 molecules released by astrocytes in synapse stabilization

thrombospondin & cholesterol