Gap Junctional Coupling between Retinal Amacrine and Ganglion Cells Underlies Coherent Spike Activity Integral to Global Object Perception

Abstract

Coherent spike activity between neighboring cells is a ubiquitous phenomenon exhibited by ensembles of neurons throughout the central nervous system, including the retina. In addition to the robust coherent activity between neighboring retinal ganglion cells (RGCs), there is evidence that widely separated RGCs can also show correlated spiking. These long range correlations can be evoked by large, contiguous light stimuli, but not to smaller, discontinuous objects. It has thus been posited that long range spike correlations between distant RGCs encode information critical to global object perception. Since the wide separation of the RGCs precludes common excitatory drive from bipolar cells, the mechanism underlying long range concerted activity has remained elusive. Most RGCs show gap junctional coupling to polyaxonal amacrine cells (PACs), which maintain extensive axonal arbors that can extend >1mm across the retina. The electrical coupling between RGCs and PACs thereby form a plausible circuit that can underlie long range correlated activity in the retina. In the current study we tested this hypothesis by targeting and recording from pairs of widely separated ON α-RGCs in the mouse retina, which are coupled indirectly through intermediary PACs. Pharmacological blockade of gap junctions or genetic ablation of connexin36 (Cx36) subunits eliminated the long range correlated spiking between the α-RGCs. These data indicated that electrical coupling between RGCs and PACs was responsible for the long range spike activity. In contrast, I found that direct, serial RGC-RGC coupling was incapable of supporting long range spike correlations. Finally, behavioral experiments were performed to test whether blockade of retinal gap junctions or ablation of Cx36 attenuates the ability of mice to discriminate large, global objects from small, disjointed stimuli. I found that Cx36 knockout mice indeed have significantly reduced ability to discriminate global objects from smaller discontinuous stimuli as compared to wild type littermates. This reduced perception of global objects was not due to a general reduction in spatial acuity that measured in knockout animals was similar to that for wild type mice. Taken together, our results indicate that long range concerted firing between RGCs, derived from electrical coupling with amacrine cells, encodes information critical to global object perception.