The cholinergic neurons of the rabbit retina, also known as starburst amacrine cells on account of their unique morphology, are a class of excitatory amacrine cells which provide a direct input to certain types of ganglion cells, including the directionally selective group. At the present time, the function of the cholinergic amacrine cells and the role of ACh in regulating ganglion cell firing rate are unknown. The PI proposes to conduct a pharmacological investigation of the cholinergic system in the rabbit retina using a broadly integrated approach which includes: 1) a study of the mechanisms controlling ACh release and 2) recording from individual neurons to evaluate the effects of cholinergic input. Using a well established release technique, the PI will identify the excitatory input to the cholinergic amacrine cells. Since this system is known to receive direct input from bipolar cells, these experiments will also provide information on the identity of the bipolar cell transmitter. Single flash experiments will be used to separate the ON and OFF components in the light-evoked release of ACh. This will permit a comparison of the excitatory and inhibitory inputs to the displaced (ON) and conventional (OFF) cholinergic amacrine cells. By extracellular recording, combined with pharmacology, the PI will compare the light-driven cholinergic input to brisk and complex ganglion cells. Specific experiments will be conducted to investigate interactions between the cholinergic and GABAergic systems. By intracellular recording, the PI will test the hypothesis that only ganglion cells receive cholinergic input. The mechanism of cholinergic excitation may be deduced by measuring changes in input resistance. For directionally selective ganglion cells, ACh and GABA inputs will be isolated and compared. The goal of these experiments is to understand the function of the cholinergic neurons in the rabbit retina. This will be one step toward an understanding of the neuronal circuits which underlie the receptive field properties of retinal ganglion cells.
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