GABAergic Inhibition Masks Rod Signals in Many Ganglion Cells in the Mouse Retina

Purpose: : To determine whether the variation in ganglion cell dark-adapted thresholds in the mouse (Dean et al., 2002; Volgyi et al. 2004) reflects selective inhibition of signals derived from the different rod pathways.

Methods: : A green (lambda = 525 nm) LED was used to deliver full-field visual stimuli to the retina at various scotopic, mesopic, and photopic intensities. Multielectrode (60 channel) extracellular or whole cell patch-clamp recordings were obtained from ganglion cells in the wild-type (WT) and connexin36 knockout (Cx36 KO) mouse retinas. Cells were classified based on their dark-adapted response thresholds and intensity-response functions.

Results: : As previously reported (Deans et al., 2002: Volgyi et al., 2004), dark-adapted mouse ganglion cells could be differentiated into the high-, intermediate-, and low-sensitivity categories based on their thresholds and intensity-response profiles. Our hypothesis was that this variation was due to selective inhibition of rod signals derived from certain of the multiple rod pathways rather than selective innervation. To test this idea, we applied the non-selective GABA blocker picrotoxin (PTX) and assessed any changes in response sensitivity. Application of 100 µM PTX had no effect on the sensitivity of high-sensitivity ganglion cells. However, it produced an increase in the sensitivity of low-sensitivity cells by either one (37 %) or two (42%) log units. Further, it increased the sensitivity of intermediate cells by one log unit (39%). Thus, PTX changed the classification of many low- and intermediate-sensitivity cells to the intermediate- and high-sensitivity categories. These data suggest a selective masking of signals in ganglion cells derived from the different rod pathways and that PTX unmasks these signals. Consistent with this idea, we found that PTX had no effect on the sensitivity of ganglion cells in the Cx36 KO retina in which the primary and secondary rod pathways are not functional.

Conclusions: : Our results indicate that GABAergic inhibition masks rod signals in many ganglion cells in the mouse retina derived from the different rod pathways. The variation seen in the sensitivity of dark-adapted ganglion cells reflects, in many cases, inhibitory masking of rod signals rather than selective innervation from the different rod pathways. GABAergic inhibition thus appears to define and limit the operating range of ganglion cells under dim light conditions.