Inhibitory Masking of ON and OFF Signals in Mammalian Ganglion Cells

Purpose: : To determine how common is the inhibitory masking of ON and OFF signals in mammalian ganglion cells. Methods: : Extracellular recordings were obtained from ganglion cells in the wild-type mouse and rabbit retinas under dark-adapted conditions using a 60-channel multielectrode array. Cells were classified as ON or OFF based on their response to a full-field light stimulus under control conditions and after application of a number of GABA receptor or gap junction blockers. Results: : We have previously reported that application of the non-selective GABA receptor blocker picrotoxin (PTX) unmasks ON signals in OFF alpha ganglion cells and OFF signals in ON direction-selective ganglion cells (Farajian et al., 2009; Ackert et al., 2009). Here, we determined how common this masking phenomenon is by recording from >100 ganglion cells in the mouse and rabbit retinas. Application of 100 µM PTX unmasked an ON response in a sizeable number of OFF ganglion cells in both rabbit (13%) and mouse (12%) retinas. Likewise, PTX unmasked a robust OFF response in a number of ON ganglion cells in the rabbit (19%) and mouse (22%) retinas. We also found that application of the GABAA receptor blocker SR-95531 (10 µM) or the GABAC receptor blocker TPMPA (100 µM) could unmask ON or OFF responses in certain ganglion cells. Application of the gap junction blockers meclofenamic acid (100 µM) or 18-β-glycyrrhetinic acid (25 µM) blocked the unmasked ON or OFF responses (73% of cells in rabbit, and 100% in mouse). Conclusions: : Our results indicate that the masking of ON and OFF signals in ganglion cells by GABAergic inhibition is common in the mammalian retina. Feedback and/or feedforward inhibition in the IPL likely underlie the masking of these ON and OFF responses. The source of the masked excitatory ON or OFF signals appears to be, in most cases, derived from electrical synapses between ganglion and amacrine cells. Overall, our findings suggest that the classification of a sizeable number ganglion cells as ON or OFF can be equivocal.