Activity-regulated cell death contributes to the formation of ON and OFF ganglion cell mosaics

Document Type

Journal Article

Publication Date

5-11-1998

Journal

Journal of Comparative Neurology

Volume

394

Issue

3

DOI

10.1002/(SICI)1096-9861(19980511)394:3<335::AID-CNE5>3.0.CO;2-2

Keywords

Cell death; Development; Mosaic patterns; Retinal ganglion cells; Sodium voltage-gated activity

Abstract

At maturity, ON and OFF α ganglion cells in the cat retina are arrayed in regular mosaics, with adjacent cells commonly forming ON-OFF pairs. In the present study, we investigated the role of activity-mediated ganglion cell death in the formation of such cellular patterns. Because direct measures of ganglion cell mosaics are problematic in the developing retina, we examined the distributions of ON and OFF α cells in the postnatal cat retina by assessing the degree to which cells in closest proximity were of opposite sign (i.e., ON-OFF pairs). Computer simulations demonstrated that superimposition of two regular distributions results in a high incidence (~90%) of opposite sign pairs. This is also the case for ON and OFF α cells in the mature retina, reflecting the high degree of regularity exhibited by this cell class. In contrast, during the first postnatal month, α cells displayed a much lower incidence of opposite sign pairs (~60%), comparable to the superimposition of two simulated random distributions. We also show that there is a 20% loss of α cells in the central retina during postnatal development and that this magnitude of loss is sufficient to form regular distributions of ON and OFF cells. To assess the influence of sodium voltage- gated activity on this developmental process, intraocular injections of tetrodotoxin (TTX) were made during the postnatal period of cell loss. When the TTX-treated animals reached maturity, there was a dose-related decrease in the incidence of opposite sign pairs, without any appreciable change in cell density. Moreover, the regularity index of ON and OFF cells was significantly lower than normal in the TTX-treated retinas. These findings demonstrate that a spatially selective pattern of ganglion cell loss contributes to the formation of regular ON and OFF ganglion cell distributions and that such cell loss is regulated by retinal activity.

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