Electrical Synapses Underlie the Concerted Spike Activity of Neighboring Ganglion Cells in the Mouse Retina

Purpose: : To determine the contribution of electrical synapses to various forms of concerted spiking activity between mouse retinal ganglion cells (GCs).

Methods: : Extracellular recordings were obtained from dark-adapted GCs in wild-type (WT) and connexin36 (Cx36) knockout (KO) mouse retinas using either a multielectrode array or a pair of Tungsten electrodes. Cross-correlation functions (CCFs) upon spontaneous spikes were generated for cell pairs. Gaussian fits were used to determine the offset (x0), amplitude (A), and width (w) of each function. Pharmacological blockade of chemical or electrical synaptic transmission was performed by using a cocktail of drugs (50µM MK-801, 10µM CNQX, 50µM PTX, 5µM STR and 50µM APB) or 18β-glycyrrhetinic acid (25µM). In addition, pairs of neighbor OFF alpha GCs were targeted, recorded and injected with Neurobiotin. Tracer coupling patterns and spike correlations were then compared for cell pairs in the WT and Cx36 KO mouse.

Results: : Based on CCF features, spike correlations of WT GC pairs were differentiated into reciprocal narrow, divergent medium, and broad scale spike correlations. We found that narrow and medium correlations were eliminated by a blockade of signals transmitted via gap junctions but were unaffected when chemical synapses were blocked. However, most narrow and some medium correlations survived in the Cx36 KO retina. These results indicate that narrow and medium spike correlations are both mediated by electrical synapses, but those that serve medium correlations are largely depend on Cx36 while those mediating narrow synchrony are Cx36 independent. In contrast, broad spike correlations were eliminated by a blockade of chemical synaptic activity in the WT retina and were entirely absent in the Cx36 KO mouse. Thus, broad spike correlations appear to be transmitted to GCs via the Cx36 dependent primary rod pathway. We also found a strong relationship between GC-to-GC tracer-coupling and narrow CCFs for OFF alpha GC pairs in both WT and Cx36 KO retinas. In contrast, both amacrine (AC)-to-GC tracer-coupling and medium CCFs characteristic features of WT OFF alpha GCs were lost in the Cx36 KO.

Conclusions: : Our results indicate that narrow spike correlations are mediated by direct GC-to-GC, whereas medium correlations are generated by GC-to-AC coupling. In contrast, signals underlying broad spike correlations appear to be transmitted via both electrical and chemical synapses within the primary rod pathway. Overall, we found that all types of concerted GC spike activity are dependent on different patterns of electrical synaptic transmission.