Abstract
Abstract: :
I demonstrate relative preservation of broad groups of surviving retinal ganglion cells, based on light–evoked responses with altered stimulus–response relationships, at an intermediate stage of retinal degeneration in the rd1 mouse, a genetic model of retinitis pigmentosa. I previously reported that as rd1 ganglion cells lose photoreceptor input, they develop hyperexcitability in the form of increased spontaneous activity. Purpose: To quantify the light–evoked responses of surviving retinal ganglion cells that are retained at a stage of significant photoreceptor loss in the rd1 mouse. Methods: Extracellular action potentials were recorded simultaneously from 30–90 retinal ganglion cells in the in vitro retina of wild type (wt) or rd1 mice, using a multielectrode array. A series of full field light flashes of five graded intensities was presented in randomized order. Responses were averaged over ten repetitions of this series, and broad groups of ganglion cells were recognized according to the relative proportion of response to light onset or offset, and to response latency and duration. The total number of spikes comprising each response was used to generate stimulus–response (S–R) curves. Results: At postnatal day 14–15 (P14–15), the proportion of ganglion cells comprising each of the broad response groups was similar between rd1 and wt mice. S–R curves for many, but not all, groups revealed decreased slope and maximal response, with responses to light offset generally being less altered than those to light onset. Thus, in the face of a declining number of functional photoreceptor inputs, for a limited time broad response groups of ganglion cells remain recognizable. Many ganglion cells of various groups display both spontaneous hyperexcitability and decreased light responsiveness. Conclusions: These results suggest the possibility that such hyperexcitability may reflect alterations in inner retinal physiology that can only partially and temporarily preserve normal responses to light. The precise mechanism of such changes, and whether they are intrinsic to the ganglion cells or occur in the inner retinal circuitry presynaptic to them, remains to be determined.
Keywords: retinal degenerations: cell biology • ganglion cells • electrophysiology: non-clinical