Abstract
Abstract: :
I present initial multielectrode recordings showing how surviving retinal ganglion cells respond to progressive loss of their normal inputs in a hereditary photoreceptor degeneration. Recent anatomic investigations have disclosed a number of changes in pathways of the outer retina that accompany and even precede the degeneration of photoreceptors in several genetic models of these diseases, including the rd1 mouse. Yet ganglion cells and other inner retinal neurons appear relatively well preserved anatomically. Purpose: To investigate the function of surviving retinal ganglion cells during the process of outer retinal degeneration. Methods: I used extracellular multielectrode recording techniques to monitor simultaneously the spontaneous spike activity of 30–50 retinal ganglion cells in the in vitro retina of wild type (wt) or rd1 mice. Results: At early developmental stages (prior to eye opening), rd1 ganglion cells participate in spontaneous "waves" of correlated firing that appear identical to those observed in wt mice. Shortly after eye opening, these waves fall silent in both rd1 and wt retinas. By early adulthood, after photoreceptors have degenerated to the point that light–evoked responses effectively have disappeared, surviving rd1 ganglion cells fire at a higher spontaneous frequency that those of wt mice. Many discharge in brief, high frequency rhythmic bursts that are clearly distinct from the developmental "waves," with a more rapid time course and with much less evident correlation among different ganglion cells. In still older animals, the rhythmic firing disappears and spontaneous activity decreases to a very low level. Conclusions: These results provide information about physiologic function in the inner retina in hereditary retinal degenerations. The identification of a limited time window during which these changes take place may promote better understanding of endogenous adaptive mechanisms, and perhaps suggest new therapeutic strategies.
Keywords: retinal degenerations: cell biology • ganglion cells • electrophysiology: non–clinical