In vivo electroretinographic studies of the role of GABAC receptors in retinal signal processing
Abstract
The retina expresses all three classes of receptors for the inhibitory neurotransmitter GABA (GABAR). Our study investigated roles of GABAR, especially GABA(C)R (GABA(A)-rho), in retinal signaling in vivo by studying effects on the mouse electroretinogram (ERG) of genetic deletion of GABA(C)R versus pharmacological blockade using receptor antagonists. Brief full-field flash ERGs were recorded from anesthetized GABA(C)R(-/-) mice, and WT C57BL/6 (B6) mice, before and after intravitreal injection of GABA(C)R antagonists, TPMPA, 3-APMPA, or the more recently developed 2-AEMP; GABA(A)R antagonist, SR95531; GABA(B)R antagonist, CGP, and agonist, baclofen. Intravitreal injections of TPMPA and SR95531 were also made in Brown Norway rats. The effect of 2-AEMP on GABA-induced current was tested directly in isolated rat rod bipolar cells, and 2-AEMP was found to preferentially block GABA(C)R in those cells. Maximum amplitudes of dark (DA) and light-adapted (LA) ERG b-waves were reduced in GABA(C)R(-/-) mice, compared to B6 mice, by 30-60%; a-waves were unaltered and oscillatory potential amplitudes were increased. In B6 mice, after injection of TPMPA (also in rats), 3-APMPA or 2-AEMP, ERGs became similar to ERGs of GABA(C)R(-/-) mice. Blockade of GABA(A)Rs and GABA(B)Rs, or agonism of GABA(B)Rs did not alter B6 DA b-wave amplitude. Furthermore, the negative scotopic threshold responsemore »
- Authors:
-
[1]
- Univ. of Houston, TX (United States). College of Optometry
- Univ. of Houston, TX (United States). College of Optometry; Texas Tech Univ., Lubbock, TX (United States). Dept. of Neurobiology
- Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States). Biosciences Division; Chengdu Kanghong Pharmaceutical Co., Sichuan (People's Republic of China)
- Univ. of Illinois, Chicago, IL (United States). Lions of Illinois Eye Research Inst.; Brown Univ., Providence, RI (United States). Lifespan Cardiovascular Inst. and Warren Alpert School of Medicine
- Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States). Biosciences Division; Univ. of Tennessee, Knoxville, TN (United States). Dept. of Biochemistry and Molecular and Cellular Biology
- Univ. of Illinois, Chicago, IL (United States). Lions of Illinois Eye Research Inst.; National Inst. of Health (NIH), Bethesda, MD (United States). National Eye Inst.
- Univ. of Illinois, Chicago, IL (United States). Lions of Illinois Eye Research Inst.
- Publication Date:
- Research Org.:
- Oak Ridge National Laboratory (ORNL), Oak Ridge, TN (United States)
- Sponsoring Org.:
- USDOE
- OSTI Identifier:
- 1334449
- Grant/Contract Number:
- AC05-00OR22725
- Resource Type:
- Accepted Manuscript
- Journal Name:
- Experimental Eye Research
- Additional Journal Information:
- Journal Volume: 139; Journal Issue: C; Journal ID: ISSN 0014-4835
- Publisher:
- Elsevier
- Country of Publication:
- United States
- Language:
- English
- Subject:
- 59 BASIC BIOLOGICAL SCIENCES; Electroretinogram; GABA; GABA receptors; Retina; Retinal signaling; DARK-ADAPTED ELECTRORETINOGRAM; ROD BIPOLAR CELLS; SCOTOPIC THRESHOLD RESPONSE; GAMMA-AMINOBUTYRIC-ACID; MOUSE RETINA; CAT RETINA; RAT RETINA; B-WAVE; HORIZONTAL CELLS; TRANSMITTER RELEASE
Citation Formats
Wang, Jing, Mojumder, Deb Kumar, Yan, Jun, Xie, An, Standaert, Robert F., Qian, Haohua, Pepperberg, David R., and Frishman, Laura J. In vivo electroretinographic studies of the role of GABAC receptors in retinal signal processing. United States: N. p., 2015.
Web. doi:10.1016/j.exer.2015.07.002.
Wang, Jing, Mojumder, Deb Kumar, Yan, Jun, Xie, An, Standaert, Robert F., Qian, Haohua, Pepperberg, David R., & Frishman, Laura J. In vivo electroretinographic studies of the role of GABAC receptors in retinal signal processing. United States. https://doi.org/10.1016/j.exer.2015.07.002
Wang, Jing, Mojumder, Deb Kumar, Yan, Jun, Xie, An, Standaert, Robert F., Qian, Haohua, Pepperberg, David R., and Frishman, Laura J. Wed .
"In vivo electroretinographic studies of the role of GABAC receptors in retinal signal processing". United States. https://doi.org/10.1016/j.exer.2015.07.002. https://www.osti.gov/servlets/purl/1334449.
@article{osti_1334449,
title = {In vivo electroretinographic studies of the role of GABAC receptors in retinal signal processing},
author = {Wang, Jing and Mojumder, Deb Kumar and Yan, Jun and Xie, An and Standaert, Robert F. and Qian, Haohua and Pepperberg, David R. and Frishman, Laura J.},
abstractNote = {The retina expresses all three classes of receptors for the inhibitory neurotransmitter GABA (GABAR). Our study investigated roles of GABAR, especially GABA(C)R (GABA(A)-rho), in retinal signaling in vivo by studying effects on the mouse electroretinogram (ERG) of genetic deletion of GABA(C)R versus pharmacological blockade using receptor antagonists. Brief full-field flash ERGs were recorded from anesthetized GABA(C)R(-/-) mice, and WT C57BL/6 (B6) mice, before and after intravitreal injection of GABA(C)R antagonists, TPMPA, 3-APMPA, or the more recently developed 2-AEMP; GABA(A)R antagonist, SR95531; GABA(B)R antagonist, CGP, and agonist, baclofen. Intravitreal injections of TPMPA and SR95531 were also made in Brown Norway rats. The effect of 2-AEMP on GABA-induced current was tested directly in isolated rat rod bipolar cells, and 2-AEMP was found to preferentially block GABA(C)R in those cells. Maximum amplitudes of dark (DA) and light-adapted (LA) ERG b-waves were reduced in GABA(C)R(-/-) mice, compared to B6 mice, by 30-60%; a-waves were unaltered and oscillatory potential amplitudes were increased. In B6 mice, after injection of TPMPA (also in rats), 3-APMPA or 2-AEMP, ERGs became similar to ERGs of GABA(C)R(-/-) mice. Blockade of GABA(A)Rs and GABA(B)Rs, or agonism of GABA(B)Rs did not alter B6 DA b-wave amplitude. Furthermore, the negative scotopic threshold response (nSTR) was slightly less sensitive in GABA(C)R(-/-) than in B6 mice, and unaltered by 2-AEMP. However, amplitudes of nSTR and photopic negative response (PhNR), both of which originate from inner retina, were enhanced by TPMPA and 3-APMPA, each of which has GABA(B) agonist properties, and further increased by baclofen. The finding that genetic deletion of GABA(C)R, the GABA(C)R antagonist 2-AEMP, and other antagonists all reduced ERG b-wave amplitude, supports a role for CABA(C)R in determining the maximum response amplitude of bipolar cells contributing to the b-wave. GABA(C)R antagonists differed in their effects on nSTR and PhNR; antagonists with GABA(B) agonist properties enhanced light-driven responses whereas 2-AEMP did not.},
doi = {10.1016/j.exer.2015.07.002},
journal = {Experimental Eye Research},
number = C,
volume = 139,
place = {United States},
year = {Wed Jul 08 00:00:00 EDT 2015},
month = {Wed Jul 08 00:00:00 EDT 2015}
}
Free Publicly Available Full Text
Publisher's Version of Record
Other availability
Search WorldCat to find libraries that may hold this journal
Cited by: 10 works
Citation information provided by
Web of Science
Web of Science
Save to My Library
You must Sign In or Create an Account in order to save documents to your library.
Works referenced in this record:
Genetic Dissection of Rod and Cone Pathways in the Dark-Adapted Mouse Retina
journal, September 2009
- Abd-El-Barr, Muhammad M.; Pennesi, Mark E.; Saszik, Shannon M.
- Journal of Neurophysiology, Vol. 102, Issue 3
Action and localization of glycine and taurine in the cat retina.
journal, May 1985
- Bolz, J.; Thier, P.; Voigt, T.
- The Journal of Physiology, Vol. 362, Issue 1
Phosphorus analogs of .gamma.-aminobutyric acid, a new class of anticonvulsants
journal, May 1984
- Cates, Lindley A.; Li, Ven Shun; Yakshe, Chriss C.
- Journal of Medicinal Chemistry, Vol. 27, Issue 5
Mechanisms Underlying Lateral GABAergic Feedback onto Rod Bipolar Cells in Rat Retina
journal, February 2010
- Chávez, Andrés E.; Grimes, William N.; Diamond, Jeffrey S.
- The Journal of Neuroscience, Vol. 30, Issue 6
Phosphonic acid analogs of GABA through reductive dealkylation of phosphonic diesters with lithium trialkylborohydrides
journal, July 2007
- Chowdhury, Sarwat; Muni, Niraj J.; Greenwood, Nicholas P.
- Bioorganic & Medicinal Chemistry Letters, Vol. 17, Issue 13
The Photopic Negative Response of the Mouse Electroretinogram: Reduction by Acute Elevation of Intraocular Pressure
journal, July 2013
- Chrysostomou, Vicki; Crowston, Jonathan G.
- Investigative Opthalmology & Visual Science, Vol. 54, Issue 7
Mammalian retinal horizontal cells are unconventional GABAergic neurons
journal, December 2010
- Deniz, Sercan; Wersinger, Eric; Schwab, Yannick
- Journal of Neurochemistry, Vol. 116, Issue 3
GABAc feedback pathway modulates the amplitude and kinetics of ERG b-wave in a mammalian retina in vivo
journal, April 2002
- Dong, Cun-Jian; Hare, William A.
- Vision Research, Vol. 42, Issue 9
GABAA, GABACand glycine receptor-mediated inhibition differentially affects light-evoked signalling from mouse retinal rod bipolar cells
journal, March 2006
- Eggers, Erika D.; Lukasiewicz, Peter D.
- The Journal of Physiology, Vol. 572, Issue 1
Receptor and Transmitter Release Properties Set the Time Course of Retinal Inhibition
journal, September 2006
- Eggers, Erika D.; Lukasiewicz, Peter D.
- The Journal of Neuroscience, Vol. 26, Issue 37
Multiple pathways of inhibition shape bipolar cell responses in the retina
journal, October 2010
- Eggers, Erika D.; Lukasiewicz, Peter D.
- Visual Neuroscience, Vol. 28, Issue 1
Presynaptic inhibition differentially shapes transmission in distinct circuits in the mouse retina
journal, July 2007
- Eggers, Erika D.; McCall, Maureen A.; Lukasiewicz, Peter D.
- The Journal of Physiology, Vol. 582, Issue 2
Molecular composition of GABAC receptors
journal, May 1998
- Enz, Ralf; Cutting, Garry R.
- Vision Research, Vol. 38, Issue 10
Immunocytochemical Localization of the GABACReceptor ρ Subunits in the Mammalian Retina
journal, July 1996
- Enz, Ralf; Brandstätter, Johann Helmut; Wässle, Heinz
- The Journal of Neuroscience, Vol. 16, Issue 14
Different Contributions of GABAAand GABACReceptors to Rod and Cone Bipolar Cells in a Rat Retinal Slice Preparation
journal, March 1998
- Euler, Thomas; Wässle, Heinz
- Journal of Neurophysiology, Vol. 79, Issue 3
Pharmacology of GABA receptor CI− channels in rat retinal bipolar cells
journal, January 1993
- Feigenspan, Andreas; Wässle, Heinz; Bormann, Joachim
- Nature, Vol. 361, Issue 6408
Light-evoked increases in [K+]o in proximal portion of the dark-adapted cat retina
journal, June 1989
- Frishman, L. J.; Steinberg, R. H.
- Journal of Neurophysiology, Vol. 61, Issue 6
Functional role of GABA in cat retina: I. Effects of GABAA agonists
journal, July 1995
- Frumkes, Thomas E.; Nelson, Ralph
- Visual Neuroscience, Vol. 12, Issue 4
The human rod ERG: Correlation with psychophysical responses in light and dark adaptation
journal, January 1978
- Fulton, Anne B.; Rushton, William A. H.
- Vision Research, Vol. 18, Issue 7
Immunocytochemical analysis of the mouse retina
journal, January 2000
- Haverkamp, Silke; W�ssle, Heinz
- The Journal of Comparative Neurology, Vol. 424, Issue 1
Rod Vision Is Controlled by Dopamine-Dependent Sensitization of Rod Bipolar Cells by GABA
journal, October 2011
- Herrmann, Rolf; Heflin, Stephanie J.; Hammond, Timothy
- Neuron, Vol. 72, Issue 1
A quantitative measure of the electrical activity of human rod photoreceptors using electroretinography
journal, October 1990
- Hood, Donald C.; Birch, David G.
- Visual Neuroscience, Vol. 5, Issue 04
GABA Transporters Regulate Inhibition in the Retina by Limiting GABAC Receptor Activation
journal, April 2002
- Ichinose, Tomomi; Lukasiewicz, Peter D.
- The Journal of Neuroscience, Vol. 22, Issue 8
Activation of the Tonic GABACReceptor Current in Retinal Bipolar Cell Terminals by Nonvesicular GABA Release
journal, August 2009
- Jones, S. M.; Palmer, M. J.
- Journal of Neurophysiology, Vol. 102, Issue 2
Opposite effects of GABAA and GABAC receptor antagonists on the b-wave of ERG recorded from the isolated rat retina
journal, June 2000
- Kapousta-Bruneau, Natalia V.
- Vision Research, Vol. 40, Issue 13
Synaptic clustering of GABA
C
receptor ρ‐subunits in the rat retina
journal, January 1998
- Koulen, Peter; Brandstätter, Johann Helmut; Enz, Ralf
- European Journal of Neuroscience, Vol. 10, Issue 1
Presynaptic and postsynaptic localization of GABAB receptors in neurons of the rat retina
journal, April 1998
- Koulen, Peter; Malitschek, Barbara; Kuhn, Rainer
- European Journal of Neuroscience, Vol. 10, Issue 4
GABAa and GABAc receptor mediated influences on the intensity-response functions of the b- and d-wave in the frog ERG
journal, March 2008
- Kupenova, P.; Popova, E.; Vitanova, L.
- Vision Research, Vol. 48, Issue 7
A diversity of GABA receptors in the retina
journal, June 1998
- Lukasiewicz, Peter D.; Shields, Colleen R.
- Seminars in Cell & Developmental Biology, Vol. 9, Issue 3
GABAC receptor-mediated inhibition in the retina
journal, December 2004
- Lukasiewicz, Peter D.; Eggers, Erika D.; Sagdullaev, Botir T.
- Vision Research, Vol. 44, Issue 28
Elimination of the ρ1 Subunit Abolishes GABACReceptor Expression and Alters Visual Processing in the Mouse Retina
journal, May 2002
- McCall, Maureen A.; Lukasiewicz, Peter D.; Gregg, Ronald G.
- The Journal of Neuroscience, Vol. 22, Issue 10
Retinal pathway origins of the pattern ERG of the mouse
journal, June 2009
- Miura, Gen; Wang, Minhua H.; Ivers, Kevin M.
- Experimental Eye Research, Vol. 89, Issue 1
Topical Mydriatics Affect Light-Evoked Retinal Responses in Anesthetized Mice
journal, January 2010
- Mojumder, Deb Kumar; Wensel, Theodore G.
- Investigative Opthalmology & Visual Science, Vol. 51, Issue 1
Actions of GABAergic ligands on brisk ganglion cells in the cat retina
journal, October 1992
- Müller, Frank; Boos, Reimund; Wässle, Heinz
- Visual Neuroscience, Vol. 9, Issue 3-4
The Müller cell: a functional element of the retina
journal, August 1996
- Newman, Eric; Reichenbach, Andreas
- Trends in Neurosciences, Vol. 19, Issue 8
Localization of γ-aminobutyric acid (GABA) receptor ρ3 subunit in rat retina
journal, March 1997
- Ogurusu, Tarou; Eguchi, Goro; Shingai, Ryuzo
- NeuroReport, Vol. 8, Issue 4
Novel GABA responses from rod- driven retinal horizontal cells
journal, January 1993
- Qian, Haohua; Dowling, John E.
- Nature, Vol. 361, Issue 6408
Pharmacology of novel GABA receptors found on rod horizontal cells of the white perch retina
journal, July 1994
- Qian, H.; Dowling, Je
- The Journal of Neuroscience, Vol. 14, Issue 7
GABAA and GABAC receptors on hybrid bass retinal bipolar cells
journal, November 1995
- Qian, H.; Dowling, J. E.
- Journal of Neurophysiology, Vol. 74, Issue 5
Response linearity and kinetics of the cat retina: The bipolar cell component of the dark-adapted electroretinogram
journal, September 1995
- Robson, J. G.; Frishman, L. J.
- Visual Neuroscience, Vol. 12, Issue 5
Rod and cone contributions to the
a
‐wave of the electroretinogram of the macaque
journal, March 2003
- Robson, John G.; Saszik, Shannon M.; Ahmed, Jameel
- The Journal of Physiology, Vol. 547, Issue 2
In vivo studies of signaling in rod pathways of the mouse using the electroretinogram
journal, December 2004
- Robson, J. G.; Maeda, H.; Saszik, S. M.
- Vision Research, Vol. 44, Issue 28
The Scotopic Threshold Response of the Dark‐Adapted Electroretinogram of the Mouse
journal, September 2002
- Saszik, Shannon M.; Robson, John G.; Frishman, Laura J.
- The Journal of Physiology, Vol. 543, Issue 3
Metabotropic GABA receptors facilitate L‐type and inhibit N‐type calcium channels in single salamander retinal neurons
journal, May 1999
- Shen, Wen; Slaughter, Malcolm M.
- The Journal of Physiology, Vol. 516, Issue 3
Scotopic threshold response of proximal retina in cat
journal, October 1986
- Sieving, P. A.; Frishman, L. J.; Steinberg, R. H.
- Journal of Neurophysiology, Vol. 56, Issue 4
Push–pull model of the primate photopic electroretinogram: A role for hyperpolarizing neurons in shaping the b-wave
journal, May 1994
- Sieving, Paul A.; Murayama, Koichiro; Naarendorp, Franklin
- Visual Neuroscience, Vol. 11, Issue 3
Differential effects of baclofen on sustained and transient cells in the mudpuppy retina
journal, February 1989
- Slaughter, M. M.; Bai, S. H.
- Journal of Neurophysiology, Vol. 61, Issue 2
Baclofen inhibits guinea pig magnocellular neurones via activation of an inwardly rectifying K+ conductance
journal, August 2003
- Slugg, R. M.; Zheng, S. -X.; Fang, Y.
- The Journal of Physiology, Vol. 551, Issue 1
Voltage-gated sodium channels contribute to the b-wave of the rodent electroretinogram by mediating input to rod bipolar cell GABAc receptors
journal, November 2013
- Smith, Benjamin J.; Tremblay, François; Côté, Patrice D.
- Experimental Eye Research, Vol. 116
GABABreceptor feedback regulation of bipolar cell transmitter release
journal, December 2010
- Song, Yunbo; Slaughter, Malcolm M.
- The Journal of Physiology, Vol. 588, Issue 24
Pharmacology of the GABAB receptor in amphibian retina
journal, October 1994
- Tian, Ning; Slaughter, Malcolm M.
- Brain Research, Vol. 660, Issue 2
trans
-4-Amino-2-methylbut-2-enoic acid (2-MeTACA) and (±)-trans
-2-aminomethylcyclopropanecarboxylic acid ((±)-TAMP) can differentiate rat ρ3 from human ρ1 and ρ2 recombinant GABAC
receptors
journal, February 2002
- Vien, Jimmy; Duke, Rujee K.; Mewett, Kenneth N.
- British Journal of Pharmacology, Vol. 135, Issue 4
Oscillatory potentials in the retina: what do they reveal
journal, October 1998
- Wachtmeister, Lillemor
- Progress in Retinal and Eye Research, Vol. 17, Issue 4
2-Aminoethyl Methylphosphonate, a Potent and Rapidly Acting Antagonist of GABAA-ρ1 Receptors
journal, August 2011
- Xie, An; Yan, Jun; Yue, Lan
- Molecular Pharmacology, Vol. 80, Issue 6
Differential localization of GABAB receptors in the mouse retina
journal, October 1998
- Zhang, Congxiao; Bettler, Bernhard; Duvoisin, Robert M.
- NeuroReport, Vol. 9, Issue 15
Works referencing / citing this record:
Contribution of GABAa, GABAc and glycine receptors to rat dark-adapted oscillatory potentials in the time and frequency domain
journal, September 2017
- Dai, Jiaman; He, Juncai; Wang, Gang
- Oncotarget, Vol. 8, Issue 44