Grant: Discovery Grants Program - Individual

Synaptic transmission is one of the most fundamental processes of the nervous system function involving the release of neurotransmitters from the presynaptic neuron, the subsequent binding of the transmitter to receptors and signal transduction at the postsynaptic neuron. In a textbook description of synaptic transmission, an action potential triggers neurotransmitter release from the presynaptic neuron (evoked release). However, neurotransmitters are also released without action potentials at virtually every synapse (spontaneous release). Recent research findings suggest that spontaneous transmitter release has significant effects on the postsynaptic neuron, including its electrical activity, protein synthesis, cell signaling and morphology. Therefore, we can conclude that spontaneous release conveys a significant physiological message at synapses, a role that could be distinct from that of precisely-timed evoked release. Despite its importance, the mechanisms underlying the regulation of spontaneous release remain poorly understood. We have been investigating the properties, modulation and plasticity of the spontaneous release of excitatory transmitter glutamate in order to understand how it is regulated. Building upon our past studies, we will determine the cellular mechanisms underlying the presynaptic modulation and plasticity of the spontaneous release of excitatory transmitter glutamate, and whether or not spontaneous glutamate release is regulated independently of evoked release. Given the pervasiveness of spontaneous neurotransmitter release, addressing these important fundamental questions will be paramount for the understanding of the physiology and pathology of the nervous system.