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Genetic targeting and physiological features of VGLUT3+ amacrine cells

Published online by Cambridge University Press:  25 August 2011

WILLIAM N. GRIMES ,
REBECCA P. SEAL ,
NICHOLAS OESCH ,
ROBERT H. EDWARDS  and
JEFFREY S. DIAMOND
WILLIAM N. GRIMES
Affiliation:
Synaptic Physiology Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland
REBECCA P. SEAL
Affiliation:
Department of Neurobiology, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania
NICHOLAS OESCH
Affiliation:
Synaptic Physiology Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland
ROBERT H. EDWARDS
Affiliation:
Departments of Physiology and Neurology, School of Medicine, University of California, San Francisco, California
JEFFREY S. DIAMOND*
Affiliation:
Synaptic Physiology Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland
*
†Address correspondence and reprint requests to: Dr. Jeffrey S. Diamond, Synaptic Physiology Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, 35 Convent Drive, Building 35, Room 3C-1000, Bethesda, MD 20892-3701. E-mail: [email protected]
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Abstract

Amacrine cells constitute a diverse class of interneurons that contribute to visual signal processing in the inner retina, but surprisingly, little is known about the physiology of most amacrine cell subtypes. Here, we have taken advantage of the sparse expression of vesicular glutamate transporter 3 (VGLUT3) in the mammalian retina to target the expression of yellow fluorescent protein (YFP) to a unique population of amacrine cells using a new transgenic mouse line. Electrophysiological recordings made from YFP-positive (VGLUT3+) amacrine cells provide the first functional data regarding the active membrane properties and synaptic connections of this recently identified cell type. We found that VGLUT3+ amacrine cells receive direct synaptic input from bipolar cells via both N-methyl-d-aspartate receptors (NMDARs) and non-NMDARs. Voltage-gated sodium channels amplified these excitatory inputs but repetitive spiking was never observed. VGLUT3+ amacrine cells responded transiently to both light increments (ON response) and decrements (OFF response); ON responses consisted exclusively of inhibitory inputs, while OFF responses comprised both excitatory and inhibitory components, although the inhibitory conductance was larger in amplitude and longer in time course. The physiological properties and anatomical features of the VGLUT3+ amacrine cells suggest that this bistratified interneuron may play a role in disinhibitory signaling and/or crossover inhibition between parallel pathways in the retina.

Keywords

InterneuronsTransgenic Cre miceSynaptic physiology
Type
Research Articles
Information
Visual Neuroscience , Volume 28 , Issue 5 , September 2011 , pp. 381 - 392
Copyright
Copyright © Cambridge University Press 2011

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References

Bieda, M.C. & Copenhagen, D.R. (1999). Sodium action potentials are not required for light-evoked release of GABA or glycine from retinal amacrine cells. Journal of Neurophysiology 81, 3092–3095.CrossRefGoogle ScholarPubMed
Bloomfield, S.A. & Xin, D. (2000). Surround inhibition of mammalian AII amacrine cells is generated in the proximal retina. The Journal of Physiology 523(Pt 3), 771–783.CrossRefGoogle ScholarPubMed
Borg-Graham, L.J. (2001). The computation of directional selectivity in the retina occurs presynaptic to the ganglion cell. Nature Neuroscience 4, 176–183.CrossRefGoogle ScholarPubMed
Chavez, A.E. & Diamond, J.S. (2008). Diverse mechanisms underlie glycinergic feedback transmission onto rod bipolar cells in rat retina. The Journal of Neuroscience 28, 7919–7928.CrossRefGoogle ScholarPubMed
Chavez, A.E., Grimes, W.N. & Diamond, J.S. (2010). Mechanisms underlying lateral GABAergic feedback onto rod bipolar cells in rat retina. The Journal of Neuroscience 30, 2330–2339.CrossRefGoogle ScholarPubMed
Chavez, A.E., Singer, J.H. & Diamond, J.S. (2006). Fast neurotransmitter release triggered by Ca influx through AMPA-type glutamate receptors. Nature 443, 705–708.CrossRefGoogle ScholarPubMed
Cook, P.B., Lukasiewicz, P.D. & McReynolds, J.S. (1998). Action potentials are required for the lateral transmission of glycinergic transient inhibition in the amphibian retina. The Journal of Neuroscience 18, 2301–2308.CrossRefGoogle ScholarPubMed
Eggers, E.D. & Lukasiewicz, P.D. (2010 a). Interneuron circuits tune inhibition in retinal bipolar cells. Journal of Neurophysiology 103, 25–37.CrossRefGoogle ScholarPubMed
Eggers, E.D. & Lukasiewicz, P.D. (2010 b). Multiple pathways of inhibition shape bipolar cell responses in the retina. Visual Neuroscience 28, 95–108.CrossRefGoogle ScholarPubMed
Euler, T., Detwiler, P.B. & Denk, W. (2002). Directionally selective calcium signals in dendrites of starburst amacrine cells. Nature 418, 845–852.CrossRefGoogle ScholarPubMed
Fremeau, R.T. Jr, Burman, J., Qureshi, T., Tran, C.H., Proctor, J., Johnson, J., Zhang, H., Sulzer, D., Copenhagen, D.R., Storm-Mathisen, J., Reimer, R.J., Chaudhry, F.A. & Edwards, R.H. (2002). The identification of vesicular glutamate transporter 3 suggests novel modes of signaling by glutamate. Proceedings of the National Academy of Sciences of the United States of America 99, 14488–14493.CrossRefGoogle ScholarPubMed
Gong, J., Jellali, A., Mutterer, J., Sahel, J.A., Rendon, A. & Picaud, S. (2006). Distribution of vesicular glutamate transporters in rat and human retina. Brain Research 1082, 73–85.CrossRefGoogle ScholarPubMed
Gras, C., Herzog, E., Bellenchi, G.C., Bernard, V., Ravassard, P., Pohl, M., Gasnier, B., Giros, B. & El Mestikawy, S. (2002). A third vesicular glutamate transporter expressed by cholinergic and serotoninergic neurons. The Journal of Neuroscience 22, 5442–5451.CrossRefGoogle ScholarPubMed
Gras, C., Vinatier, J., Amilhon, B., Guerci, A., Christov, C., Ravassard, P., Giros, B. & El Mestikawy, S. (2005). Developmentally regulated expression of VGLUT3 during early post-natal life. Neuropharmacology 49, 901–911.CrossRefGoogle ScholarPubMed
Grimes, W.N., Li, W., Chavez, A.E. & Diamond, J.S. (2009). BK channels modulate pre- and postsynaptic signaling at reciprocal synapses in retina. Nature Neuroscience 12, 585–592.CrossRefGoogle ScholarPubMed
Grimes, W.N., Zhang, J., Graydon, C.W., Kachar, B. & Diamond, J.S. (2010). Retinal parallel processors: More than 100 independent microcircuits operate within a single interneuron. Neuron 65, 873–885.CrossRefGoogle ScholarPubMed
Hartveit, E. (1999). Reciprocal synaptic interactions between rod bipolar cells and amacrine cells in the rat retina. Journal of Neurophysiology 81, 2923–2936.CrossRefGoogle ScholarPubMed
Haverkamp, S. & Wassle, H. (2004). Characterization of an amacrine cell type of the mammalian retina immunoreactive for vesicular glutamate transporter 3. The Journal of Comparative Neurology 468, 251–263.CrossRefGoogle ScholarPubMed
Hsueh, H.A., Molnar, A. & Werblin, F.S. (2008). Amacrine-to-amacrine cell inhibition in the rabbit retina. Journal of Neurophysiology 100, 2077–2088.CrossRefGoogle ScholarPubMed
Ichinose, T. & Lukasiewicz, P.D. (2005). Inner and outer retinal pathways both contribute to surround inhibition of salamander ganglion cells. The Journal of Physiology 565, 517–535.CrossRefGoogle ScholarPubMed
Johnson, J., Sherry, D.M., Liu, X., Fremeau, R.T. Jr, Seal, R.P., Edwards, R.H. & Copenhagen, D.R. (2004). Vesicular glutamate transporter 3 expression identifies glutamatergic amacrine cells in the rodent retina. The Journal of Comparative Neurology 477, 386–398.CrossRefGoogle ScholarPubMed
MacNeil, M.A., Heussy, J.K., Dacheux, R.F., Raviola, E. & Masland, R.H. (1999). The shapes and numbers of amacrine cells: Matching of photofilled with Golgi-stained cells in the rabbit retina and comparison with other mammalian species. The Journal of Comparative Neurology 413, 305–326.3.0.CO;2-E>CrossRefGoogle ScholarPubMed
MacNeil, M.A. & Masland, R.H. (1998). Extreme diversity among amacrine cells: Implications for function. Neuron 20, 971–982.CrossRefGoogle ScholarPubMed
Manookin, M.B., Beaudoin, D.L., Ernst, Z.R., Flagel, L.J. & Demb, J.B. (2008). Disinhibition combines with excitation to extend the operating range of the OFF visual pathway in daylight. The Journal of Neuroscience 28, 4136–4150.CrossRefGoogle ScholarPubMed
Molnar, A., Hsueh, H.A., Roska, B. & Werblin, F.S. (2009). Crossover inhibition in the retina: Circuitry that compensates for nonlinear rectifying synaptic transmission. Journal of Computational Neuroscience 27, 569–590.CrossRefGoogle ScholarPubMed
Munch, T.A., da Silveira, R.A., Siegert, S., Viney, T.J., Awatramani, G.B. & Roska, B. (2009). Approach sensitivity in the retina processed by a multifunctional neural circuit. Nature Neuroscience 12, 1308–1316.CrossRefGoogle ScholarPubMed
Murphy, G.J. & Rieke, F. (2008). Signals and noise in an inhibitory interneuron diverge to control activity in nearby retinal ganglion cells. Nature Neuroscience 11, 318–326.CrossRefGoogle Scholar
Oesch, N.W. & Taylor, W.R. (2010). Tetrodotoxin-resistant sodium channels contribute to directional responses in starburst amacrine cells. PLoS One 5, e12447.CrossRefGoogle ScholarPubMed
Pang, J.J., Gao, F. & Wu, S.M. (2003). Light-evoked excitatory and inhibitory synaptic inputs to ON and OFF alpha ganglion cells in the mouse retina. The Journal of Neuroscience 23, 6063–6073.CrossRefGoogle Scholar
Protti, D.A., Gerschenfeld, H.M. & Llano, I. (1997). GABAergic and glycinergic IPSCs in ganglion cells of rat retinal slices. The Journal of Neuroscience 17, 6075–6085.CrossRefGoogle ScholarPubMed
Schafer, M.K., Varoqui, H., Defamie, N., Weihe, E. & Erickson, J.D. (2002). Molecular cloning and functional identification of mouse vesicular glutamate transporter 3 and its expression in subsets of novel excitatory neurons. The Journal of Biological Chemistry 277, 50734–50748.CrossRefGoogle ScholarPubMed
Siegert, S., Scherf, B.G., Del Punta, K., Didkovsky, N., Heintz, N., Roska, B. (2009). Genetic address book for retinal cell types. Nature Neuroscience 12, 1197–1204.CrossRefGoogle ScholarPubMed
Singer, J.H. & Diamond, J.S. (2003). Sustained Ca2+ entry elicits transient postsynaptic currents at a retinal ribbon synapse. The Journal of Neuroscience 23, 10923–10933.CrossRefGoogle Scholar
Stella, S.L. Jr, Li, S., Sabatini, A., Vila, A. & Brecha, N.C. (2008). Comparison of the ontogeny of the vesicular glutamate transporter 3 (VGLUT3) with VGLUT1 and VGLUT2 in the rat retina. Brain Research 1215, 20–29.CrossRefGoogle ScholarPubMed
Taylor, W.R. & Vaney, D.I. (2002). Diverse synaptic mechanisms generate direction selectivity in the rabbit retina. The Journal of Neuroscience 22, 7712–7720.CrossRefGoogle ScholarPubMed
Vaney, D.I. & Taylor, W.R. (2002). Direction selectivity in the retina. Current Opinion in Neurobiology 12, 405–410.CrossRefGoogle ScholarPubMed
van Wyk, M., Wassle, H. & Taylor, W.R. (2009). Receptive field properties of ON- and OFF-ganglion cells in the mouse retina. Visual Neuroscience 26, 297–308.CrossRefGoogle Scholar
Wallner, M., Meera, P. & Toro, L. (1999). Molecular basis of fast inactivation in voltage and Ca2+-activated K+ channels: A transmembrane beta-subunit homolog. Proceedings of the National Academy of Sciences of the United States of America 96, 4137–4142.CrossRefGoogle ScholarPubMed
Xia, X.M., Ding, J.P. & Lingle, C.J. (1999). Molecular basis for the inactivation of Ca2+- and voltage-dependent BK channels in adrenal chromaffin cells and rat insulinoma tumor cells. The Journal of Neuroscience 19, 5255–5264.CrossRefGoogle ScholarPubMed
Yang, X.W., Model, P. & Heintz, N. (1997). Homologous recombination based modification in Escherichia coli and germline transmission in transgenic mice of a bacterial artificial chromosome. Nature Biotechnology 15, 859–865.CrossRefGoogle ScholarPubMed
Zhang, J., Jung, C.S. & Slaughter, M.M. (1997). Serial inhibitory synapses in retina. Visual Neuroscience 14, 553–563.CrossRefGoogle ScholarPubMed
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