Abstract
Excitability differs among muscle fibers and undergoes continuous changes during development and growth, yet the neuromuscular synapse maintains a remarkable fidelity of execution. Here we show in two evolutionarily distant vertebrates (Xenopus laevis cell culture and mouse nerve-muscle ex-vivo) that the skeletal muscle cell constantly senses, through two identified calcium signals, synaptic events and their efficacy in eliciting spikes. These sensors trigger retrograde signal(s) that control presynaptic neurotransmitter release, resulting in synaptic potentiation or depression. In the absence of spikes, synaptic events trigger potentiation. Once the synapse is sufficiently strong to initiate spiking, the occurrence of these spikes activates a negative retrograde feedback. These opposing signals dynamically balance the synapse in order to continuously adjust neurotransmitter release to a level matching current muscle cell excitability.
Highlights
In the nervous system, presynaptic neurotransmitter release, postsynaptic receptors, and postsynaptic excitability can be modulated to bi-directionally and durably change synaptic efficacy
In Xenopus cultures, we found that the nicotinic conductance activated in muscle cells by spike-evoked ACh release varied linearly with the postsynaptic input conductances measured in a population of synaptic neuron/muscle cell pairs (Figure 1C), and resulted in comparable evoked postsynaptic potentials (ePSP) voltage amplitudes
We have demonstrated in two evolutionarily distant vertebrate species that the skeletal muscle cell constantly senses the synaptic events and their ability to trigger postsynaptic action-potentials
Summary
Presynaptic neurotransmitter release, postsynaptic receptors, and postsynaptic excitability can be modulated to bi-directionally and durably change synaptic efficacy. Each skeletal muscle fiber is mono-innervated (Sanes and Lichtman, 1999), and each single presynaptic action potential (AP) induces one postsynaptic AP, corresponding to a unity synaptic gain (ratio between the numbers of post- and presynaptic APs equal to 1) (Wood and Slater, 2001). The stability of the gain implies that presynaptic neurotransmitter release and/or postsynaptic receptors adapt the effective synaptic strength to the excitability of the muscle fiber, which depends on the fiber characteristics, and presumably decreases with growth and exercise (Turrigiano, 2007). In adult vertebrate skeletal muscles, cholinergic nicotinic receptors are clustered in the synaptic region.
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