Synaptic transmission in the rod pathway of the mammalian retina

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DESCRIPTION (provided by applicant): This proposal will support investigation of pre- and postsynaptic mechanisms contributing to the reproducibility, timing, and dynamic range of signaling at the rod bipolar-All amacrine cell synapse in the rod pathway of the mammalian retina. The long-term goal of this research is to understand how visual information is encoded by synaptic interactions between retinal neurons. Three specific aims will be addressed using electrophysiological recordings from synaptically coupled neurons in a retinal slice preparation. Specific aim 1 investigates the presynaptic basis of reproducibility. The hypothesis that the kinetic properties of the presynaptic calcium channel, the retina-specific Cav1.4, and its placement relative to release sites in the active zone allow changes in presynaptic membrane potential to be transmitted reliably by the synapse will be tested. Specific aim 2 will examine presynaptic mechanisms that control the timing of neurotransmitter release from rod bipolar cell terminals and investigate the hypothesis that activity-dependent modulation of the proteins composing the release machinery alters the kinetics of exocytosis. Specific aim 3 will examine postsynaptic mechanisms controlling the dynamic range of the synapse. The hypothesis that voltage-gated sodium and potassium channels in the All membrane act to amplify small synaptic conductances and limit changes in the dynamic range of the synapse during activity-dependent synaptic depression will be addressed. Together, these specific aims will serve to elucidate the mechanisms that permit the normal function of retinal synapses during visual processing. This is a necessary first step in understanding altered retinal function in pathological states affecting vision. In particular, as mutations in Cav1.4 are responsible for X-linked incomplete congenital stationary night blindness, understanding the role that these channels play normally in synaptic transmission may provide insight into this disease.