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Electrophysiological evidence of GABAA and GABAC receptors on zebrafish retinal bipolar cells


To refine inhibitory circuitry models for ON and OFF pathways in zebrafish retina, GABAergic properties of zebrafish bipolar cells were studied with two techniques: whole cell patch responses to GABA puffs in retinal slice, and voltage probe responses in isolated cells. Retinal slices documented predominantly axon terminal responses; isolated cells revealed mainly soma-dendritic responses. In the slice, GABA elicited a conductance increase, GABA responses were more robust at axon terminals than dendrites, and Erev varied with [Cl]in. Axon terminals of ON- and OFF-type cells were similarly sensitive to GABA (30–40 pA peak current); axotomized cells were unresponsive. Bicuculline-sensitive, picrotoxin-sensitive, and picrotoxin-insensitive components were identified. Muscimol was as effective as GABA; baclofen was ineffective. Isolated bipolar cells were either intact or axotomized. Even in cells without an axon, GABA or muscimol (but not baclofen) hyperpolarized dendritic and somatic regions, suggesting significant distal expression. Median fluorescence change for GABA was −0.22 log units (∼ −16 mV); median half-amplitude dose was 0.4 μM. Reduced [Cl]out blocked GABA responses. GABA hyperpolarized isolated ON-bipolar cells; OFF-cells were either unresponsive or depolarized. Hyperpolarizing GABA responses in isolated cells were bicuculline and TPMPA insensitive, but blocked or partially blocked by picrotoxin or zinc. In summary, axon terminals contain bicuculline-sensitive GABAA receptors and both picrotoxin-sensitive and insensitive GABAC receptors. Dendritic processes express zinc- and picrotoxin-sensitive GABAC receptors.

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Address correspondence and reprint requests to: V.P. Connaughton, Department of Biology, American University, 4400 Massachusetts Ave, NW, Washington, DC 20016. E-mail:
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R. Blanco , C.F. Vaquero & P. de la Villa (1996). The effects of GABA and glycine on horizontal cells of the rabbit retina. Vision Research 36, 39873995.

V.P. Connaughton (2003). Zebrafish retinal slice preparation. Methods in Cell Science 25, 4958.

V.P. Connaughton , T.N. Behar , W.-L.S. Liu & S. Massey (1999). Immunocytochemical localization of excitatory and inhibitory neurotransmitters in the zebrafish retina. Visual Neuroscience 16, 483490.

V.P. Connaughton & J.E. Dowling (1998). Comparative morphology of distal neurons in developing and adult zebrafish retinas. Vision Research 38, 1318.

V.P. Connaughton & G. Maguire (1998). Differential expression of voltage-gated K+ and Ca+2 currents in bipolar cells in the zebrafish retinal slice. European Journal of Neuroscience 10, 13501362.

J. Crooks & H. Kolb (1992). Localization of GABA, glycine, glutamate, and tyrosine hydroxylase in the human retina. Journal of Comparative Neurology 315, 287302.

C.-J. Dong & W.A. Hare (2002). GABAC feedback pathway modulates the amplitude and kinetics of ERG b-wave in a mammalian retina in vivo. Vision Research 42, 10811087.

J.-L. Du & X.-L. Yang (2002a). Bullfrog retinal bipolar cells may express heterogeneous glycine receptors at dendrites and axon terminals. Neuroscience Letters 322, 177181.

J.-L. Du & X.-L. Yang (2002b). Glycinergic synaptic transmission to bullfrog retinal bipolar cells is input-specific. Neuroscience 113, 779784.

E.D. Eggers & P. Lukasiewicz (2006). GABAA, GABAC, and glycine receptor-mediated inhibition differentially affects light-evoked signalling from mouse retinal rod bipolar cells. Journal of Physiology 572, 215225.

A. Feigenspan & J. Bormann (1994). Differential pharmacology of GABAA and GABAC receptors on rat retinal bipolar cells. European Journal of Pharmacology 288, 97104.

A. Feigenspan , H. Wässle & J. Bormann (1993). Pharmacology of GABA receptor Cl-channels in rat retinal bipolar cells. Nature 361, 159161.

M.J. Frech & K.H. Backus (2004). Characterization of inhibitory postsynaptic currents in rod bipolar cells of the mouse retina. Visual Neuroscience 21, 645652.

M.A. Freed , R.G. Smith & P. Sterling (2003). Timing of quantal release from the retinal bipolar terminal is regulated by a feedback circuit. Neuron 38, 89101.

M.-H. Han & X.-L. Yang (1999). Zn+2 differentially modulates kinetics of GABAC vs. GABAA receptors in carp retinal bipolar cells. Neuroreport 10, 25932597.

R. Hanitzsch , L. Kuppers & A. Flade (2004). The effect of GABA and the GABA-uptake-blocker NO-711 on the b-wave of the ERG and the responses of horizontal cells to light. Graefe's Archive of Clinical Experimental Ophthalmology 242, 784791.

R. Heidelberger & G. Matthews (1991). Inhibition of calcium influx and calcium current by gamma-aminobutyric acid in single synaptic terminals. Proceeding of the National Academy of Science 88, 71357139.

C. Hull , G.-L. Li & H. von Gersdorff (2006). GABA transporters regulate a standing GABAC receptor-mediated current at a retinal presynaptic terminal. Journal of Neuroscience 26, 69796984.

C. Hull & H. von Gersdorff (2004). Fast endocytosis is inhibited by GABA-mediated chloride influx at a presynaptic terminal. Neuron 44, 469482.

E. Ivanova , E. Muller & H. Wässle (2006). Characterization of the glycinergic input to bipolar cells of the mouse retina. European Journal of Neuroscience 23, 350364.

M. Kaneda , B. Andrasfalvy & A. Kaneko (2000). Modulation of Zn+2 of GABA responses in bipolar cells of the mouse retina. Visual Neuroscience 17, 273281.

N.V. Kapousta-Bruneau (2000). Opposite effects of GABAA and GABAC receptor antagonists on the b-wave of the ERG recorded from the isolated rat retina. Vision Research 40, 16531665.

H. Kolb & J. Jones (1984). Synaptic organization of the outer plexiform layer of the turtle retina: An electron microscope study of serial sections. Journal of Neurocytology 13, 567591.

H. Kolb & R.W. West (1977). Synaptic connections of the interplexiform cell in the retina of the cat. Journal of Neurocytology 6, 155170.

H. Kondo & J.-I. Toyoda (1983). GABA and glycine effects on the bipolar cells of the carp retina. Vision Research 23, 12591264.

A. Lasansky (1973). Organization of the outer synaptic layer in the retina of the larval tiger salamander. Philosophical Transactions of the Royal Society London B-Biological Sciences 265, 471489.

K.A. Linberg & S.K. Fisher (1988). Ultrastructural evidence that horizontal cell axon terminals are presynaptic in the human retina. Journal of Comparative Neurology 268, 281297.

A.F. Mack , U.D. Behrens & H.-J. Wagner (2000). Inhibitory control of synaptic activity in goldfish Mb bipolar cell terminals visualized by FM1-43. Visual Neuroscience 17, 823829.

G. Maguire , B. Maple , P. Lukasiewicz & F.S. Werblin (1989). Gamma-aminobutyric type B receptor modulation of L-type calcium channel current at bipolar cell terminals in the retina of the tiger salamander. Proceeding of the National Academy of Science 86, 1014410147.

B.R. Maple & S.M. Wu (1998). Glycinergic synaptic inputs to bipolar cells in the tiger salamander retina. Journal of Physiology 506, 731744.

R.E. Marc & D. Cameron (2001). A molecular phenotype atlas of the zebrafish retina. Journal of Neurocytology 30, 593654.

R.E. Marc , W.K. Stell , D. Bok & D.M. Lam (1978). GABAergic pathways in the goldfish retina. Journal of Comparative Neurology 182, 221224.

G.S. McGillem , T.C. Rotolo & R.F. Dacheux (2000). GABA responses of rod bipolar cells in rabbit retinal slices. Visual Neuroscience 17, 381389.

R. Nelson , A.M. Bender & V.P. Connaughton (2003). Stimulation of sodium pump restores membrane potential to neurons excited by glutamate in zebrafish distal retina. Journal of Physiology 549, 787800.

R. Nelson , A.E. Schaffner , Y.-X. Li & M.K. Walton (1999). Distribution of GABAC-like responses among acutely dissociated rat retinal neurons. Visual Neuroscience 16, 179190.

Y. Pan , P. Khalili , H. Ripps & H. Qian (2005). Pharmacology of GABAC receptors: Responses to agonists and antagonists distinguish A- and B-subtypes of homomeric rho receptors expressed in Xenopus oocytes. Neuroscience Letters 376, 6065.

Z.-H. Pan (2001). Voltage-activated Ca+2 channels and ionotropic GABA receptors localized at axon terminals of mammalian retinal bipolar cells. Visual Neuroscience 18, 279288.

R.G. Pourcho & D.J. Goebel (1983). Neuronal subpopulations in cat retina which accumulate the GABA agonist, (3H)muscimol: A combined Golgi and autoradiographic study. Journal of Comparative Neurology 219, 2535.

H. Qian , J.E. Dowling & H. Ripps (1998). Molecular and pharmacological properties of GABA-rho subunits from white perch retina. Journal of Neurobiology 37, 305320.

H. Qian , R.P. Malchow , R.L. Chappell & H. Ripps (1996). Zinc enhances ionic currents induced in skate Muller (glial) cells by the inhibitory neurotransmitter GABA. Proceeding of the Royal Society of London B 263, 791796.

H. Qian & Y. Pan (2002). Co-assembly of GABA rho subunits with GABAA receptor gamma-2 subunit cloned from white perch retina. Molecular Brain Research 103, 6270.

H. Qian & H. Ripps (1999). Response kinetics and pharmacological properties of hetermoeric receptors formed by coassembly of GABA rho- and gamma2-subunits. Proceeding of the Royal Society of London B 266, 24192425.

H. Qian , H. Ripps , E. Schuette & R.L. Chappell (2001). Responses of small- and large-field bipolar cells to GABA and glycine. Brain Research 893, 273277.

Y. Shen , L. Chen , Y. Ping & X.-L. Yang (2005). Glycine modulates the center response of ON type rod-dominant bipolar cells in carp retina. Brain Research Bulletin 67, 492497.

C.F. Vaquero & P. de la Villa (1999). Localisation of the GABAC receptors at the axon terminal of rod bipolar cells of the mouse retina. Neuroscience Research 35, 17.

S.M. Wu (1986). Effects of gamma-aminobutyric acid on cones and bipolar cells of the tiger salamander retina. Brain Research 365, 7077.

S.M. Wu & B. Maple (1998). Amino acid neurotransmitters in the retina: A functional overview. Vision Research 38, 13711384.

S. Yazulla , K.M. Studholme & J.Y. Wu (1987). GABAergic input to the synaptic terminals of Mb1 bipolar cells in the goldfish retina. Brain Research 411, 400405.

D. Zhang , Z.-H. Pan , X. Zhang , A.D. Brideau & S.A. Lipton (1995). Cloning of a gamma-aminobutyric acid type C receptor subunit in rat retina with methionine residue critical for picrotoxinin channel block. Proceeding of the National Academy of Science 92, 1175611760.

D.-O. Zhang & X.-L. Yang (1997). OFF pathway is preferentially suppressed by the activation of GABAA receptors in carp retina. Brain Research 759, 160162.

J. Zhang , A.L. De Blas , C.P. Miralles & C.-Y. Yang (2003). Localization of GABAA receptor subunits alpha1, alpha3, beta1, beta2/3, gamma1, and gamma2 in the salamander retina. Journal of Comparative Neurology 459, 440453.

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Visual Neuroscience
  • ISSN: 0952-5238
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