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The Journal of Neuroscience, May 15, 2002, 22(10):4163-4174

Elimination of the 1 Subunit Abolishes GABA_C Receptor Expression and Alters Visual Processing in the Mouse Retina

Maureen A. McCall^{1, 2}, Peter D. Lukasiewicz⁴, Ronald G. Gregg^{2, 3}, and Neal S. Peachey^{5, 6, 7}

Departments of ¹ Psychological and Brain Sciences, ² Ophthalmology and Visual Sciences, and ³ Biochemistry and Molecular Biology, University of Louisville, Louisville, Kentucky 40292, ⁴ Department of Ophthalmology and Visual Sciences, Washington University, St. Louis, Missouri 63110, ⁵ Cleveland Veterans Affairs Medical Center, Cleveland, Ohio 44106, ⁶ Cole Eye Institute, Cleveland Clinic Foundation, Cleveland, Ohio 44195, and ⁷ Department of Neurosciences, Case Western Reserve University, Cleveland, Ohio 44106

Inhibition is crucial for normal function in the nervous system. In the CNS, inhibition is mediated primarily by the amino acid GABA via activation of two ionotropic GABA receptors, GABA_A and GABA_C. GABA_A receptor composition and function have been well characterized, whereas much less is known about native GABA_C receptors. Differences in molecular composition, anatomical distributions, and physiological properties strongly suggest that GABA_A receptors and GABA_C receptors have distinct functional roles in the CNS. To determine the functional role of GABA_C receptors, we eliminated their expression in mice using a knock-out strategy. Although native rodent GABA_C receptors are composed of 1 and 2 subunits, we show that after 1 subunit expression was selectively eliminated there was no GABA_C receptor expression. We assessed GABA_C receptor function in the retina because GABA_C receptors are highly expressed on the axon terminals of rod bipolar cells and because this site modulates the visual signal to amacrine and ganglion cells. In GABA_C1 null mice, GABA-evoked responses, normally mediated by GABA_C receptors, were eliminated, and signaling from rod bipolar cells to third order cells was altered. These data demonstrate that elimination of the GABA_C1 subunit, via gene targeting, results in the absence of GABA_C receptors in the retina and selective alterations in normal visual processing.

Key words: knock-out; rod bipolar cell; electroretinogram; IPSC; whole-cell patch clamp; TPMPA; ionotropic receptor; chloride channel; inhibition

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Copyright © 2002 Society for Neuroscience  0270-6474/02/22104163-12$05.00/0

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