Elimination of the rho1 subunit abolishes GABA(C) receptor expression and alters visual processing in the mouse retina.
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 rho1 and rho2 subunits, we show that after rho1 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(C)rho1 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(C)rho1 subunit, via gene targeting, results in the absence of GABA(C) receptors in the retina and selective alterations in normal visual processing.
McCall
Maureen A
MA
Department of Psychological and Brain Sciences, University of Louisville, Louisville, Kentucky 40292, USA. mo.mccall@louisville.edu
Lukasiewicz
Peter D
PD
Gregg
Ronald G
RG
Peachey
Neal S
NS
D000818:Animals; D003623:Dark Adaptation / Q000502:physiology; D004596:Electroretinography / Q000187:drug effects; D018756:GABA Antagonists / Q000494:pharmacology; D018390:Gene Targeting; D066298:In Vitro Techniques; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009433:Neural Inhibition / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D018408:Patch-Clamp Techniques; D010775:Photic Stimulation / Q000379:methods; D017729:Presynaptic Terminals / Q000187:drug effects / Q000378:metabolism; D021122:Protein Subunits; D018079:Receptors, GABA / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism*; D011995:Recombination, Genetic; D012160:Retina / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D017948:Retinal Rod Photoreceptor Cells / Q000502:physiology; D017384:Sequence Deletion / Q000235:genetics; D013234:Stem Cells; D013268:Stimulation, Chemical; D014785:Vision, Ocular / Q000235:genetics / Q000502:physiology*; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology
D018756:GABA Antagonists; C087200:GABA-C receptor; D021122:Protein Subunits; D018079:Receptors, GABA; D005680:gamma-Aminobutyric Acid