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B.T. Sagdullaev, M.A. McCall, P.D. Lukasiewicz; The Modulation of Glutamate Release by GABAC Receptors Differentially Shapes Responses of ON and OFF Retinal Ganglion Cells . Invest. Ophthalmol. Vis. Sci. 2005;46(13):2274.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: To determine how GABAC receptor–mediated modulation of excitatory signals from ON and OFF bipolar cells shapes retinal outputs. Methods: Spontaneous and evoked excitatory responses were recorded from retinal ganglion cells (RGCs) in wild type (WT) and GABAC null mice. Light–evoked and spontaneous activity was recorded from single optic nerve fibers in vivo. Electrically–evoked and spontaneous excitatory postsynaptic currents (EPSCs) were recorded from RGCs in retinal slices. Results: Light–evoked and spontaneous spiking were enhanced in ON, but not OFF RGCs of GABAC null mice. To determine the underlying mechanism, we recorded monosynaptic, electrically–evoked EPSCs (eEPSCs) from RGCs. Blocking GABAC receptors increased glutamate release from ON bipolar cells, enhancing the eEPSCs in ON RGCs. In contrast, responses in OFF RGCs were not altered. Spontaneous EPSCs (sEPSCs) in ON RGCs from GABAC null mice exhibited a significant NMDA receptor–mediated component, whereas in ON RGCs from WT mice these sEPSCs were exclusively mediated by AMPA receptors. In addition, pharmacologically blocking GABAC receptors in WT mice mimicked the GABAC null mice by revealing an NMDA component in sEPSCs from ON RGCs. This suggests that GABAC–mediated inhibition limits glutamate release from ON bipolar cells and therefore decreases the spillover activation of perisynaptically localized NMDA receptors on ON RGCs. In WT mice, the dynamic range of evoked excitatory responses from OFF RGCs was narrower compared to ON RGCs and was not modulated by GABAC receptors. In contrast, the dynamic range of evoked responses from ON RGCs was decreased in mice that lacked GABAC receptors. Thus, glutamate release from ON bipolar cells and subsequent activation of postsynaptic NMDA receptors, is limited by GABAC receptor–mediated feedback, which selectively extends the dynamic range of ON RGC excitatory responses. Conclusions: We found that transmission of visual information to ganglion cells is differentially modulated by GABAC receptor–mediated inhibition. Inhibitory input via GABAC receptors selectively limits glutamate release from ON bipolar cells and spillover activation of NMDA receptors at ON, but not OFF RGCs. We show that this differential modulation of excitatory signaling in the inner retina underlies some asymmetries in the output characteristics of ON and OFF RGCs.
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