The spiking activity of retinal ganglion cells, and hence the output of the retina, is shaped by interactions between two kinds of inputs converging onto ganglion cells: excitatory signals from bipolar cells, and inhibitory signals from amacrine cells. Recent studies have shown that such interactions can result in surprisingly sophisticated computations, in which contextual features of the visual environment transiently affect a ganglion cell's response properties. For example, a ganglion cell may respond strongly to movement in the center of its receptive field, but this response can be suppressed completely if movement in the periphery is coordinated with movement in the center. Prior investigations have described several such examples of dynamic coding in the retina, which are thought to help the animal detect novel features in complex changing visual scenes. The purpose of this project is to move beyond description, by giving mechanistic explanations of how the neural circuitry of the retina is able to implement these forms of coding.
In Specific Aim #1, stimulus-evoked synaptic currents in ganglion cells will be measured and analyzed in order to distinguish the roles of excitatory and inhibitory pathways in determining the ganglion cell's response properties. The main electrophysiological technique used in this Aim will be whole-cell patch clamp recording from ganglion cells in the intact isolated retina.
In Specific Aim #2, amacrine cells will be stimulated with current injections and the activity of downstream ganglion cells will be monitored in order to determine how long-range amacrine cells influence other components of the circuit.
This Aim will draw on several electrophysiological techniques, again in the intact isolated retina: extracellular recording from ganglion cells with multielectrode arrays, intracellular stimulation of amacrine cells with sharp microelectrodes, and whole-cell patch clamp recording from ganglion cells. A detailed, mechanistic understanding of how the retina processes complex stimuli will be helpful in devising treatments for visual dysfunctions, in particular in constructing a retinal prosthesis to stimulate the optic nerves of patients with damaged photoreceptors. In designing such a machine, it is important to understand how nature's own microcircuits extract essential features of the visual environment using a relatively small number of simple components.
