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Stuart C Mangel, Andrey Dmitriev, Thomas Hirschauer; Effects of Ethanol and Low Concentration of Picrotoxin Suggest Involvement of Extra-synaptic GABAa Receptors in Direction Selectivity. Invest. Ophthalmol. Vis. Sci. 2014;55(13):4531.
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Although GABAa receptors (GABAaRs) consisting of various subunits are expressed by many retinal neurons, evidence suggests that GABAaRs that contain the δ-subunit are unique to starburst amacrine cells (SACs) (Brandstätter et al., 1995). GABAa-δRs are high-affinity receptors that are tonically active under ambient GABA concentrations and not located within synapses (Belelli et al., 2009). At blood alcohol concentrations typically associated with social consumption (50 mM), the GABAergic effects of ethanol appear to be limited to these GABAa-δRs (Wallner et al., 2003), which ethanol potentiates. Because SACs are pre-synaptic to many ganglion cell (GC) types, including direction selective (DS) GCs, we studied whether ethanol alters the light responses of DS- and non-DS GCs.
The spiking activity of rabbit GCs to stationary (spots, annuli) and moving light stimuli was recorded using the loose patch technique. In addition to studying the effects of ethanol, we also studied the effects of a low concentration (0.5-2.0 µM) of picrotoxin (PTX), which preferentially blocks tonic, extra-synaptic GABAaR currents due to its greater affinity for GABA-bound GABAaRs than for unbound ones. Concentrations of PTX 10 - 30 times higher are needed to block synaptic GABAa and GABAcRs (Walker, Semyanov, 2007).
Ethanol (20-30 mM) dramatically decreased and PTX (0.5-2.0 µM) increased the responses of ON-OFF- and ON-DS GCs to stimuli moving in all directions, thereby decreasing but not eliminating direction selectivity. Neither drug at these concentrations had an observable effect on the responses of non-DS GCs to moving stimuli. ON-DS GCs exhibited OFF responses in the presence of 2 μM PTX. Additionally, ON-DS GCs treated with low PTX began to respond to large (600 x 600 μm) moving rectangles that did not evoke responses in control conditions.
Ethanol (20-30 mM) significantly decreased and low PTX (0.5-2 μM) enhanced the responses of rabbit DS GCs to stimuli moving in all directions, but neither drug had an effect on the motion responses of non-DS GCs. These results are consistent with the idea that the extra-synaptic GABAa-δRs of SACs mediate the DS responses of ON-OFF- and ON-DS GCs. Ethanol may impair our sense of balance in part by disrupting ON-DS GC input to the accessory optic system, which mediates image stabilization (Pu, Amthor, 1990).
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