Synaptic transmission is a major mechanism underlying the intercellular transfer and processing of signals in the nervous system. The output of synapses is highly dynamic, owing to the existence of several forms of activity-dependent synaptic plasticity that range in duration from milliseconds to hours. Although individual forms of synaptic plasticity have been well described, the simple stimulus patterns used to define each form of plasticity bear little resemblance to the activity patterns seen in vivo, where most synapses are activated by temporally complex patterns of afferent firing. These complex patterns of activity are expected to engage several forms of synaptic plasticity simultaneously in a complex combination, which we will refer to as synaptic dynamics. Synaptic dynamics determine how the synaptic output produced by each spike is influenced by the pattern of the preceding spike train. These dynamics are widely presumed to be an important component of signal processing during synaptic transmission, and may be affected by drugs or neurological diseases; however, synaptic dynamics during realistic patterns of afferent activity are poorly understood. Our long-term objective is to determine the roles of synaptic dynamics in circuit function in the hippocampus, a brain structure critical in learning and memory. In the present proposal, we will examine synaptic dynamics of Schaffer collateral synapses between CA3 pyramidal cells and CA1 pyramidal cells in hippocampal slices. We will use field and whole-cell recordings to measure synaptic responses to spike trains derived from activity patterns seen in CA3 pyramidal cells in vivo during the performance of a complex behavioral task. We will address three specific aims: 1) to identify functional consequences of synaptic dynamics during behaviorally-relevant patterns of afferent activity; 2) to identify mechanisms that underlie synaptic dynamics; and 3) to determine whether synaptic dynamics can be altered by neuromodulators or long-term plasticity.
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