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Genetic targeting and physiological features of VGLUT3+ amacrine cells

  • WILLIAM N. GRIMES (a1), REBECCA P. SEAL (a2), NICHOLAS OESCH (a1), ROBERT H. EDWARDS (a3) and JEFFREY S. DIAMOND (a1)...
Abstract
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.

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Corresponding author
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: diamondj@ninds.nih.gov
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S.A. Bloomfield & D. Xin (2000). Surround inhibition of mammalian AII amacrine cells is generated in the proximal retina. The Journal of Physiology 523(Pt 3), 771783.

L.J. Borg-Graham (2001). The computation of directional selectivity in the retina occurs presynaptic to the ganglion cell. Nature Neuroscience 4, 176183.

A.E. Chavez & J.S. Diamond (2008). Diverse mechanisms underlie glycinergic feedback transmission onto rod bipolar cells in rat retina. The Journal of Neuroscience 28, 79197928.

A.E. Chavez , W.N. Grimes & J.S. Diamond (2010). Mechanisms underlying lateral GABAergic feedback onto rod bipolar cells in rat retina. The Journal of Neuroscience 30, 23302339.

A.E. Chavez , J.H. Singer & J.S. Diamond (2006). Fast neurotransmitter release triggered by Ca influx through AMPA-type glutamate receptors. Nature 443, 705708.

E.D. Eggers & P.D. Lukasiewicz (2010 a). Interneuron circuits tune inhibition in retinal bipolar cells. Journal of Neurophysiology 103, 2537.

T. Euler , P.B. Detwiler & W. Denk (2002). Directionally selective calcium signals in dendrites of starburst amacrine cells. Nature 418, 845852.

R.T. Fremeau Jr, J. Burman , T. Qureshi , C.H. Tran , J. Proctor , J. Johnson , H. Zhang , D. Sulzer , D.R. Copenhagen , J. Storm-Mathisen , R.J. Reimer , F.A. Chaudhry & R.H. Edwards (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, 1448814493.

J. Gong , A. Jellali , J. Mutterer , J.A. Sahel , A. Rendon & S. Picaud (2006). Distribution of vesicular glutamate transporters in rat and human retina. Brain Research 1082, 7385.

C. Gras , J. Vinatier , B. Amilhon , A. Guerci , C. Christov , P. Ravassard , B. Giros & S. El Mestikawy (2005). Developmentally regulated expression of VGLUT3 during early post-natal life. Neuropharmacology 49, 901911.

W.N. Grimes , W. Li , A.E. Chavez & J.S. Diamond (2009). BK channels modulate pre- and postsynaptic signaling at reciprocal synapses in retina. Nature Neuroscience 12, 585592.

W.N. Grimes , J. Zhang , C.W. Graydon , B. Kachar & J.S. Diamond (2010). Retinal parallel processors: More than 100 independent microcircuits operate within a single interneuron. Neuron 65, 873885.

S. Haverkamp & H. Wassle (2004). Characterization of an amacrine cell type of the mammalian retina immunoreactive for vesicular glutamate transporter 3. The Journal of Comparative Neurology 468, 251263.

H.A. Hsueh , A. Molnar & F.S. Werblin (2008). Amacrine-to-amacrine cell inhibition in the rabbit retina. Journal of Neurophysiology 100, 20772088.

T. Ichinose & P.D. Lukasiewicz (2005). Inner and outer retinal pathways both contribute to surround inhibition of salamander ganglion cells. The Journal of Physiology 565, 517535.

J. Johnson , D.M. Sherry , X. Liu , R.T. Fremeau Jr, R.P. Seal , R.H. Edwards & D.R. Copenhagen (2004). Vesicular glutamate transporter 3 expression identifies glutamatergic amacrine cells in the rodent retina. The Journal of Comparative Neurology 477, 386398.

M.A. MacNeil , J.K. Heussy , R.F. Dacheux , E. Raviola & R.H. Masland (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, 305326.

M.A. MacNeil & R.H. Masland (1998). Extreme diversity among amacrine cells: Implications for function. Neuron 20, 971982.

M.B. Manookin , D.L. Beaudoin , Z.R. Ernst , L.J. Flagel & J.B. Demb (2008). Disinhibition combines with excitation to extend the operating range of the OFF visual pathway in daylight. The Journal of Neuroscience 28, 41364150.

A. Molnar , H.A. Hsueh , B. Roska & F.S. Werblin (2009). Crossover inhibition in the retina: Circuitry that compensates for nonlinear rectifying synaptic transmission. Journal of Computational Neuroscience 27, 569590.

T.A. Munch , R.A. da Silveira , S. Siegert , T.J. Viney , G.B. Awatramani & B. Roska (2009). Approach sensitivity in the retina processed by a multifunctional neural circuit. Nature Neuroscience 12, 13081316.

G.J. Murphy & F. Rieke (2008). Signals and noise in an inhibitory interneuron diverge to control activity in nearby retinal ganglion cells. Nature Neuroscience 11, 318326.

N.W. Oesch & W.R. Taylor (2010). Tetrodotoxin-resistant sodium channels contribute to directional responses in starburst amacrine cells. PLoS One 5, e12447.

M.K. Schafer , H. Varoqui , N. Defamie , E. Weihe & J.D. Erickson (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, 5073450748.

S.L. Stella Jr, S. Li , A. Sabatini , A. Vila & N.C. Brecha (2008). Comparison of the ontogeny of the vesicular glutamate transporter 3 (VGLUT3) with VGLUT1 and VGLUT2 in the rat retina. Brain Research 1215, 2029.

D.I. Vaney & W.R. Taylor (2002). Direction selectivity in the retina. Current Opinion in Neurobiology 12, 405410.

M. Wallner , P. Meera & L. Toro (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, 41374142.

X.W. Yang , P. Model & N. Heintz (1997). Homologous recombination based modification in Escherichia coli and germline transmission in transgenic mice of a bacterial artificial chromosome. Nature Biotechnology 15, 859865.

J. Zhang , C.S. Jung & M.M. Slaughter (1997). Serial inhibitory synapses in retina. Visual Neuroscience 14, 553563.

S. Siegert , B.G. Scherf , K. Del Punta , N. Didkovsky , N. Heintz , B. Roska (2009). Genetic address book for retinal cell types. Nature Neuroscience 12, 11971204.

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Visual Neuroscience
  • ISSN: 0952-5238
  • EISSN: 1469-8714
  • URL: /core/journals/visual-neuroscience
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