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Raunak Sinha, Mrinalini Hoon, Rachel O Wong, Fred Rieke; Role of GABAA-receptor mediated presynaptic inhibition in shaping ON ganglion cell responses. Invest. Ophthalmol. Vis. Sci. 201657(12):.
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© ARVO (1962-2015); The Authors (2016-present)
Presynaptic inhibition on mouse retinal bipolar cells mediated by GABAergic or glycinergic amacrine cells modulates output from their axon terminals. ON bipolar cell terminals predominantly express α1-containing GABAA(GABAAα1) and GABAC receptors. How presynaptic inhibition on bipolar cells regulates ganglion cell function is not well understood in a cell-type specific manner. The goal of this study was to test how impairment of GABAA-receptor mediated presynaptic inhibition on ON bipolar cells impacts ON ganglion cell responses at low and high light levels
To eliminate GABAA receptors from ON bipolar cell terminals, we crossed GABAAα1 conditional knockout (cKO) animals with an ON bipolar cell specific Cre line. Cell-attached and whole cell patch clamp recordings from ganglion cells were carried out in a flat mount retina preparation. We targeted ON-sustained ganglion cells due to their well-characterized connectivity and functional properties. Visual stimuli were presented through computer-controlled LEDs. To determine receptor expression in control and cKO animals, immunostaining was performed using specific antibodies directed against GABA receptor subtypes.
Immunolabeling confirmed specific elimination of GABAAα1 from ON bipolar cell terminals in the GABAAα1-cKO retinas. Further, GABAC receptor levels were unaltered in the axon terminals of GABAAα1-cKO ON bipolar cells. Excitatory synaptic currents of ON-sustained ganglion cells measured in response to light flashes were altered in both kinetics and amplitude in the cKO mice compared to control. Consequently the contrast response curves under both rod and cone light levels showed significant deviations from control retinas. The altered excitatory input onto ON sustained ganglion cells in the absence of GABAAergic presynaptic inhibition also perturbed their spike output.
Our results show that targeted deletion of GABAAergic presynaptic inhibition from ON bipolar cells results in altered light responses of ON sustained ganglion cells. This underscores an essential role for GABAA-receptor mediated presynaptic inhibition in shaping bipolar cell to ganglion cell transmission of photoreceptor signals and consequently in determining the ganglion cell output.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
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