Formation and Elimination of Synapses

What molecule induces glycine (and GABA) receptors to cluster at a synapse?

Gephyrin

Rapsyn

Cross-linking protein. Aids in clustering of ACh receptors

What molecule induces Glutamate receptors to cluster at a synapse?

PSD-95 (ionotropic) Homer (metabotropic)

Lrp4

Tyrosine receptor kinase. Activated by Agrin

MuSk

Tyrosine receptor kinase. Activated by Agrin and activates Rapsyn

Why is synapse formation more complex in the CNS than it is at the neuromuscular junction?

-CNS has multiple neurotransmitters that need to be localized in different regions -CNS has multiple synapses throughout the same neuron -No basal lamina in the CNS (i.e. no Laminin Beta2)

Molecules that link pre- and post-synaptic cells together at CNS synapses

-Cadherins link pre-synaptic and post-synaptic neurons (Neurexin and Neuroligin play a role in forming and maintaining synapses)

Three mechanisms that contribute to localization of ACh receptor in neuromuscular junction

-Clustering of existing receptors -Downregulate AChR expression at distant nuclei -Upregulate AChR expression at synaptic nuclei

Agrin

Causes aggregation/re-localization of ACh receptors.

ACh receptor localization in muscle cells *after* synapse formation

High density of receptors at synapse. Expression of ACh receptors decreases further away form synapse

Signal to stop growth cone in neuromuscular junction and form synapse

Laminin with Beta2 (Laminin without Beta2 allows neuron to continue to grow and synapse is not formed)

ACh receptor localization in muscle cells *before* synapse formation

Low density of receptors that are spread out throughout the muscle cell

What would you expect to see in a denervated muscle that is artificially stimulated with electrodes?

Prevents super-sensitivity (prevents loss of electrical activity)

What would you expect to see in an innervated muscle that is paralyzed with anesthetic

Prolonged anesthetic exposure leads to super-sensitivity

Describe the action of neuregulin

Stimulates upregulation of ACh receptors in the nuclei close to the synapses

What would you expect to see in a muscle that is denervated?

Super-sensitivity. (Loss of electrical input prevents repression of ACh receptors)