Abstract
Purpose: :
Neighboring ganglion cells (GCs) in the mouse retina show different types of spontaneous correlated spike activity that are generated by electrical and/or chemical synaptic transmission. Here, we examined how these types of correlated activity are affected by changes in the dark/light adaptation of the retina.
Methods: :
Extracellular recordings were obtained from GCs in the 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) of spontaneous spiking were generated for cell pairs. Experiments were carried out in retinas initially maintained in a dark-adapted state and then light-adapted with a photopic green background light of 3000 Rh*/rod/s.
Results: :
The spontaneous, correlated activity of neighboring GCs in the dark-adapted retina could be differentiated into three types (narrow, medium, and broad) based on the shape of the CCF profiles. Blockade of chemical transmission eliminated broad correlations, but had no significant effect on the narrow or medium CCFs. Blockade of gap junctions with 18β-glycyrrhetinic acid (18-GA) eliminated all narrow and medium correlations, indicating that they are dependent on electrical synaptic transmission. Surprisingly, application of 18-GA eliminated all broad CCFs as well. We also found a decrease in the number of narrow and medium correlations in the Cx36 KO mouse retina when compared to that in the WT, but a complete loss of broad CCFs. Our results thus indicated that broad correlations are dependent on both chemical and electrical transmission, suggesting that the gap junctions involved are likely distant from the GCs, possibly in the outer retina. We found that light adaptation of the retina had no effect on narrow and medium spike correlations. However, broad correlations were completely eliminated when the retina was light adapted with a photopic background light.
Conclusions: :
Our results indicate that different synaptic pathways are responsible for generating the different types of correlated spike activity of neighboring GCs in mouse retina. In particular, we found that broad correlations were dependent on both chemical and electrical synaptic circuits. Our finding that broad correlations were abolished by deletion of Cx36 and after light adaptation suggests that they are derived from rod-driven circuitry. We posit that broad correlations reflect signals derived from the secondary rod pathway, which depends on rod-cone coupling via gap junctions known to express Cx36 in cone hemichannels. Overall, light adaptation resulted in an increase in the temporal precision of the correlated activity of neighboring GCs.
Keywords: gap junctions/coupling • ganglion cells • retinal connections, networks, circuitry