Synaptogenesis

Describe how neurons control muscle fibers with respect to ratio of control to muscle.

Alpha motor neurons connect directly to muscle fibers. For more coarse control, one neuron controls many motor units whereas in finer motor control one axon only controls one muscle fiber.

What is the role of the basal lamina?

The basal lamina is a mesh-like EM that contains AchE that breaks down Ach.

What is the role of the active zone?

Structurally, the active zone is filled with vesicles and calcium channels. In the active zone vesicles and neurotransmitters are released into the muscular junction.

Explain the difference in receptor density before innervation and after (in the muscular system).

Before neural muscular innervation there is low density of Ach receptors as well as sparse synapses. After innervation, there is a high concentration of AchR under the nerve.

Explain the mechanism that changes the density of receptors before and after innervation in the muscular system.

Agrin is responsible for localizing these synapses and receptors. When there are no synapses made, the neuron will die out. Agrin binds to MUSK (which forms dimers that interact with rapsyn). Rapsyn is an anchoring protein that creates strong affinity for AchR clustering.

What is the role of AchE?

It destroys Ach in the active zone and prevents long polarization. This is to clear the synapse in time for the next activation.

What are some molecules that are contained in the basal lamina?

The basal lamina contains AchE, and EM proteins such as laminins which stabilize signals and allow muscle-nerve regeneration, LDLPR-4 (low-density lipoprotein receptor 4) helps to amplify low levels of agrin signals to musk receptors.

What is the agrin-like molecule in the CNS?

There is no single molecule that is found to be critical like agrin, but instead there are many others. Cell adhesion molecules play much more of an important role.

Describe the general pipeline for synapse formation in the CNS.

1. CAMS cause cascade -> homeophile, heterophile binding
2. pre-, post-synaptic precursors transported to the target synapse location
3. delivering of synaptic material such as scaffolding protein
4. formation of synapse

we note that this is not a random process, but rather it is "loaded dice" in the sense that there is some genetic precursor that localizes axons.

Name a pre-, post- synaptic cadherin, and also describe their role in synapse formation as well as the detailed pipeline.

neurexin (pre), neuroligin (post) these are essential for the glutamate or GABA pathways. Both are necessary and sufficient to form synapses of this kind.

Once the CAMs find each other, we begin to recruit channel receptors and scaffolds to shape the axon, CASK is the pre-synaptic molecule responsible for this while PSD-95 is the post-synaptic molecule responsible for scaffolding.

How is synapse localization determined?

Homeobox genes encode things in neurons for growth and wiring. Neurons that wire together share parts of the same genes that are expressed together.