Regulation of calcium-secretion coupling

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Neurons communicate with each other at synapses. When the action potential reaches the presynaptic side of the synapse, the electrical signal is turned into a chemical signal through the calcium-dependent release of a synaptic vesicle. The vesicle contains neurotransmitters that then cross the synaptic cleft and are converted into an electrical signal in the postsynaptic cell through opening of neurotransmitter-gated ion channels. This complicated chemical process underlies all communication in the nervous system and presumably evolved to allow sophisticated modulation of synaptic connections, since electrical connections consisting of gap-junctions would be sufficient to just transmit the electrical signal. One of the ways this process is regulated is whether or not the action potential causes release of a synaptic vesicle. The ability to modulate the probability of transmitter release underlies much of the plasticity of the nervous system. In our program, we will elucidate fundamental mechanisms by which release is regulated using the model sensory-motor neuron synapse of the marine snail Aplysia. In this animal, behavioral habituation, the ability of the animal to ignore innocuous stimuli, is mediated by the loss of transmitter release at this synapse. A noxious stimulus, through the release of serotonin, leads both to the reversal of habituation (through regaining transmitter release at the synapse) and sensitization, through increasing transmitter release at this synapse. The modulation of these synapses can be studied in cultures, where molecular and cellular techniques can be applied to determine the mechanisms by which this regulation is mediated. This will lead to fundamental discoveries on how transmitter release is regulated and thus how synapses work.