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Jing Wang, Laura J. Frishman; Effects of GabaC or GabaA Receptor Inactivation on Mouse Electroretinogram. Invest. Ophthalmol. Vis. Sci. 2011;52(14):1609.
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© ARVO (1962-2015); The Authors (2016-present)
GABAC receptors (GABACRs) in the mouse retina are highly expressed on axon terminals of bipolar cells, particularly rod and ON cone bipolar cells, but are also present more distally on those cells. GABAARs, while present on bipolar cells, are also found on amacrine and ganglion cells, and in distal retina. This study investigated functions of these different ionotropic GABARs in retina by studying effects on mouse electroretinogram (ERG) of using receptor antagonists and agonists, or genetic deletion of GABACRs.
Dark-adapted (DA) and light-adapted (LA) brief flash ganzfeld ERGs were recorded from anesthetized C57BL/6 control mice before and after intravitreal injection of TPMPA (50 µM vitreal conc.), GABA (30 mM), GABAAR antagonist (SR95531, 50 µM) and from GABACR knockout (KO) mice. a-wave and negative scotopic threshold response (nSTR) were measured at 6 and 200 ms, respectively, after flashes. After oscillatory potentials (OPs: 50-300 Hz) were extracted, b-waves were measured at peak times: 110 ms for DA ERG, 50 ms for LA ERG. OP amplitude was quantified as root mean square (RMS).
GABACR KO or TPMPA injection in control mice significantly reduced b-wave amplitudes for stimuli > -3 log sc td s in DA ERG (above positive STR saturation), and > 1 log sc td s in LA ERG. Maximum amplitudes were reduced by 30 - 60%. a-wave, nSTR and pSTR amplitudes were unaffected. OP RMS was increased slightly in DA ERG by TPMPA or GABACR KO, and increased in LA ERG, by 15 - 35%. In contrast, SR95531 did not reduce DA or LA ERG b-wave amplitudes; it enhanced DA nSTR, and LA photopic negative response (PhNR) and reduced OPs. GABA injection increased DA and LA b-wave amplitudes for the stimulus ranges affected (oppositely) by elimination of functional GABAcRs. GABA also removed STRs, OPs, and PhNR. GABA injection in GABACR KO mice reduced, rather than increased b-wave amplitudes.
These results suggest an excitatory role for GABA via GABACRs in mouse retina. GABACRs on ON bipolar cells that generate ERG b-waves must be functional for normal maximum amplitudes to be achieved. Results for GABAARs on inner retinal ERG signals (and effects of GABAcRs on OPs) are consistent with the known inhibitory role of GABA on amacrine and ganglion cell signals.
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