Center for Brain Research
 
 
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Synapse Formation: The Neuromuscular Synapse - a Model System

Head: Ruth Herbst

"People are judged by their actions, and these actions are coordinated by nerve cells and carried out by muscle cells. So an understanding of nerve and muscle is fundamental to our knowledge of how the human body functions."
R.D. Keynes, D.J. Aidley

Synapses are essential relay stations that confer information between cells. Synapses from between neurons or as in the case of the neuromuscular synapses between a motor neuron and a muscle fiber. The neuromuscular synapse regulates every movement within our bodies including breathing and therefore is critical for survival. In addition, the neuromuscular synapse has been a popular model system for synapse formation due to its size, simplicity and accessibility. Much of the information about neurotransmitter receptor function and assembly at synaptic sites comes from studies on the neuromuscular synapse.

Neuromuscular synapses form when a motor axon reaches a muscle fiber. Signals from the nerve induce differentiation of the postsynaptic muscle membrane and in turn, signals from the muscle induce differentiation of the presynaptic nerve terminal. A hallmark of postsynaptic differentiation is the concentration of acetylcholine receptors (AChRs), the receptors for the neurotransmitter acetylcholine, at synaptic sites. AChRs are present at a concentration of 10,000 molecules per µm2 at synapses compared to 10 molecules per µm2 in the extrasynaptic membrane. This high concentration of AChRs ensures a reliable and stable transmission of action potentials to the muscle necessary to govern all movements within the lifetime of a vertebrate organism.

Three main mechanisms are involved in the clustering of AChRs at synapses: (1) pre-existing AChRs are redistributed to synaptic sites; (2) AChR genes are selectively transcribed in subsynaptic nuclei and (3) AChR genes are downregulated in non-synaptic nuclei. Our laboratory uses molecular biological and mouse molecular genetics approaches to study the molecular mechanisms that lead to neuromuscular synapse formation.

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