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Andrey V. Dmitriev, Stuart C. Mangel; Effects of Low Concentration of Picrotoxin Suggest Involvement of Extra-synaptic GABAA Receptors in Direction Selectivity. Invest. Ophthalmol. Vis. Sci. 2012;53(14):1952.
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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 delta subunit are unique to starburst amacrine cells (SACs) Brandstätter et al., 1995). It has been shown that GABAA-ΔRs are only found on extrasynaptic membranes, have a high affinity for GABA and show weak desensitization, thus producing tonic Cl- currents when activated (Belelli et al., 2009). Because SACs are pre-synaptic to many ganglion cell (GC) types, including direction selective (DS) GCs, we investigated the role of extra-synaptic GABAA-ΔRs in GC responses to stationary and moving light stimuli and in the generation of direction selectivity.
The spiking activity of various rabbit GC types to stationary (spots, annuli) and moving light stimuli was recorded using the loose patch technique. Because picrotoxin (PTX) has a greater affinity for GABA-bound GABAARs than for unbound ones, we used a low concentration (0.5-2.0 µM) of PTX to preferentially block tonic, extra-synaptic GABAAR currents. Concentrations of PTX 10 - 30 times higher are needed to block synaptic GABAA and GABACRs (Walker, Semyanov, 2007).
PTX (0.5-2.0 µM) increased GC responses to stationary stimuli, but never evoked spontaneous spiking. In the case of moving stimuli, the effects of low PTX were different for DS and non-DS GCs. PTX (0.5-2.0 µM) dramatically increased the responses of On-Off and On-DS GCs to stimuli moving in all directions, thereby decreasing but not eliminating direction selectivity, but had no 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, an effect that was previously described for 50 μM PTX (Ackert et. al., 2009). 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. Interestingly, non-DS On GCs also exhibited Off responses under low PTX.
Low PTX (0.5-2 μM) significantly enhanced the responses of DS GCs to stimuli moving in all directions, but had no effect on the motion responses of non-DS GCs. These results are consistent with the idea that the extra-synaptic, GABAA-ΔRs of SACs modulate the DS responses of On-Off and On DS GCs.
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