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Mikhail Lipin, William Rowland Taylor, Robert G Smith, ; Activation of mGluR8 Abolishes Off-Direction Selectivity in Guinea Pig Retina. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):3243.
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© ARVO (1962-2015); The Authors (2016-present)
Direction selective ganglion cells (DSGC) respond preferentially to motion in one direction. Responses in the opposite, null direction are suppressed by GABAergic inhibition from starburst amacrine cells (SBACs). Activation of the group-III metabotropic glutamate receptor mGluR8 is known to attenuate the Off-response in DSGCs (Quraishi et al., 2010), however, it is not known whether the attenuation results from augmented GABA release from starburst or other amacrine cells, or suppression of glutamate release from Off-bipolar cells. Here we determined how activation of mGluR8 receptors affects direction selectivity in On-Off DSGCs in the guinea pig retina.
We used a whole-mount guinea pig retina preparation superfused with Ames medium at 360C. The retina was stimulated with narrow dark bars (150 µm by 700 µm) with 50% light contrast moving at 400 µm/s in the preferred or null direction. We recorded extracellular spikes from DSGCs using on-cell mode. To determine light-evoked excitatory and inhibitory conductances, we used whole-cell voltage clamp mode at various holding potentials followed by off-line conductance analysis. To activate mGluR8 receptors, we used 1-3 µM (S)-3,4-DCPG.
Application of DCPG completely abolished Off-direction selectivity in DSGC (n=3) by evoking additional spikes in response to the null direction motion, while the response to the preferred direction motion was barely affected. DCPG also compromised On-direction selectivity by evoking spikes in response to the null direction motion and decreasing spikes in response to the preferred direction. In the whole cell recordings, DCPG abolished the light-evoked Off-inhibitory conductance in DSGCs (n=4), and decreased the light-evoked On-excitatory and On-inhibitory conductances.
Surprisingly, unlike the mouse retina, activation of mGluR8 receptors in the guinea pig retina abolished Off-direction selectivity by evoking a strong response to null direction motion rather than by attenuating responses to preferred direction motion. This finding suggests that mGluR8 receptors in the guinea pig retina are predominantly located on Off-SBACs rather than on Off-bipolar cell terminals, and control GABA release from SBACs.
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