RETINAL PATTERNS, GRADES SYNAPSES, NEUROMODULATION

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1) To understand the dynamic interactions among the processes of populations of bipolar and amacrine cells in the inner plexiform layer related to retinal movement and change analysis. The idea is to measure activity in the processes, not normally accessible to single cell recordings, with newly developed optical techniques. The work will utilize methods of video imaging of neural activity revealed by voltage and Calcium sensitive dyes. Preliminary results suggest that different dynamic processes occupy different strata. We will generate a picture of dynamic stratification of activity throughout the depth of the inner, plexiform layer. 2) To understand how the release of the transmitter glutamate is controlled at the graded potential synapse of the photoreceptors. It is the concentration of glutamate at these synapses that informs the postsynaptic cells of the graded levels of photoreceptor activity. The (hyperpolarizing) light response in initiated, not by the release, but by the uptake (via a transporter) of transmitter. This control appears to involve interactions between vesicular release and transporter uptake, and preliminary results suggest a titration between these two mechanisms. We will generate a picture of dynamic interactions between uptake and release involved in the control of glutamate concentrations. 3) To understand the role of newly-discovered neuromodulatory events in the retina, including dopamine modulation of GABA sensitivities in the inner and outer retina, and relate these to the overall scheme of visual processing. Preliminary results suggest that dopamine modulation of GABAc receptor sensitivity may complement or amplify earlier well-known neuromodulatory events. These studies will utilize patch clamp of single cells and of cells in living retinal slices, a technique developed by this laboratory and now universally implemented. In addition to looking at single cell events, we will use the newly-developed technique of multielectrode array recording to look carefully at changes in activity in populations of cells mediated by dopamine; effects such as changes in correlation of activity between units and changes in rates of spread of activity, that would not be visible recording from single cells.