RETINAL PHARMACOLOGY OF DIRECTIONAL GANGLION CELLS

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The research herein proposed as the continuation of grant EY05978 will further our understanding of both the functioning of retinal neurons which underly the detection of the stimulus direction by ganglion cells and the functional role which these directionally sensitive (DS) retinal output neurons play in visually evoked behaviors. DS cells are also found at many other levels of visual processing, but it is not known whether different DS cells use different mechanisms to extract directional information. Furthermore, it is not clear whether DS pathways combine or compete for their control over behavior responses. The proposed research addresses these questions by a unique combination of in vitro and in vivo electrophysiological techniques along with recording eye movements. We've shown that directionally sensitive retinal ganglion cells can be readily recorded in vitro using a healthy and stable superfused retinal eyecup preparation of the turtle. Experiments using this preparation will continue to test the effects of synaptic transmitters and their antagonists on specific response properties of the DS retinal ganglion cells. Release of the neurotransmitters GABA and ACh by amacrine cells have dramatic effects on directional sensitivity. Similarly, exogenously applied agents have direct effects on the spike firing of DS cells during synaptic blockade, suggesting that transmitter receptors are found on the ganglion cell membrane. The possibility that directional sensitivity is first formed at this level is contrary to recent reports that DS responses are recorded from biopolar cells using drifting gratings. We will test this possibility using conventional small spot stimuli after a careful mapping of the receptive field. Preliminary findings reported here show that synaptic drugs that are effective in vitro on DS retinal ganglion cells can also have clear behavioral effects when applied intravitreally. When we pharmacologically perturb the retinal processing of directional sensitivity in vivo we observe eye movement effects which appear specific to optokinetic nystagmus (OKN). OKN is an appropriate behavior to study since it requires the visual system's ability to detect stimulus direction in order for eye movements to stablize the stimulus image on the retina. This knowledge may further OKN's diagnostic usefulness in differentiating retinal versus central directional processing.