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The Journal of Neuroscience, May 15, 2002, 22(10):4163-4174
Elimination of the  1 Subunit Abolishes GABAC
Receptor Expression and Alters Visual Processing in the Mouse
Retina
Maureen A.
McCall1, 2,
Peter D.
Lukasiewicz4,
Ronald G.
Gregg2, 3, and
Neal S.
Peachey5, 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,
GABAA and GABAC. GABAA receptor
composition and function have been well characterized, whereas much
less is known about native GABAC receptors. Differences in
molecular composition, anatomical distributions, and physiological
properties strongly suggest that GABAA receptors and
GABAC receptors have distinct functional roles in the CNS. To determine the functional role of GABAC receptors, we
eliminated their expression in mice using a knock-out strategy.
Although native rodent GABAC receptors are composed of  1
and 2 subunits, we show that after 1 subunit expression was
selectively eliminated there was no GABAC receptor
expression. We assessed GABAC receptor function in the
retina because GABAC 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 GABAC1
null mice, GABA-evoked responses, normally mediated by GABAC receptors, were eliminated, and signaling from rod
bipolar cells to third order cells was altered. These data demonstrate that elimination of the GABAC1 subunit, via gene
targeting, results in the absence of GABAC 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
Copyright © 2002 Society for Neuroscience 0270-6474/02/22104163-12$05.00/0
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