Dissecting Neural Circuitry in the Mammalian Retina

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DESCRIPTION (From the Applicant's Abstract): The goal of this project is to advance our understanding of how visual information is processed by the circuitry of the retina. Retinal circuitry is divided into two layers: the outer plexiform layer (OPL) and the inner plexiform layer (IPL). While much is known about the contribution of the OPL, that of the IPL has been difficult to ascertain. The aim of this project is to determine the contributions of specific neuronal cell populations in the IPL. This will be addressed using a technique for targeted cell class ablation. The method is to genetically engineer the cell class so that it will selectively label with a photoactivatable dye. Once labeled, the cells can be killed by photoablation. This method has been tested in vivo and in vitro on several different cell classes in the mouse retina and shown to be >90 percent effective with <2 percent non-specific cell death. With this method, we can test hypotheses about the actions of a specific cell population by ablating it from the circuitry and examining the effects on retinal output. Our research is divided into two parts. The first is to characterize the response properties of the retinal output neurons, the ganglion cells, in the mouse retina. The mouse will be used as our model system, because the method for ablating cells requires gene transfer, and the mouse is amenable to genetic manipulation. The response properties of the ganglion cells will be examined by presenting the isolated retina with light patterns generated on a computer monitor and recording ganglion cell spike trains with a multi-electrode array. The second part is to determine the roles of specific populations of interneurons in shaping these ganglion cell response properties. This project focuses on two interneuron populations, i) neuropeptide-Y-expressing amacrine cells, which are proposed to play a role in shaping the behavior of ganglion cells that respond to light offset (OFF cells), and ii) catecholaminergic interplexiform cells, which are proposed, based on studies in lower vertebrates, to act on horizontal cells and bipolar cells, and, through their action, to shape the center/surround organization of ganglion cell receptive fields. These hypotheses will be tested and other actions of these cell populations will be examined by ablating them from the retina and assessing changes in ganglion cell response properties. Anatomical and neurochemical properties of these populations will also be examined to gain information about how these cells mediate their effects. These studies will provide basic information about how retinal circuits process information and insight into mechanisms that underlie circuit malfunctions.