Skip to main content
    • Aa
    • Aa
  • Get access
    Check if you have access via personal or institutional login
  • Cited by 19
  • Cited by
    This article has been cited by the following publications. This list is generated based on data provided by CrossRef.

    Seal, Rebecca P. 2016. Do the distinct synaptic properties of VGLUTs shape pain?. Neurochemistry International, Vol. 98, p. 82.

    Kim, Tahnbee Soto, Florentina and Kerschensteiner, Daniel 2015. An excitatory amacrine cell detects object motion and provides feature-selective input to ganglion cells in the mouse retina. eLife, Vol. 4,

    Krishnaswamy, Arjun Yamagata, Masahito Duan, Xin Hong, Y. Kate and Sanes, Joshua R. 2015. Sidekick 2 directs formation of a retinal circuit that detects differential motion. Nature, Vol. 524, Issue. 7566, p. 466.

    Balasubramanian, Revathi and Gan, Lin 2014. Development of Retinal Amacrine Cells and Their Dendritic Stratification. Current Ophthalmology Reports, Vol. 2, Issue. 3, p. 100.

    Atoji, Yasuro and Karim, Mohammad Rabiul 2014. Expression of vesicular glutamate transporter 3 mRNA in the brain and retina of the pigeon. Journal of Chemical Neuroanatomy, Vol. 61-62, p. 124.

    Masland, Richard H. 2012. The Neuronal Organization of the Retina. Neuron, Vol. 76, Issue. 2, p. 266.

    Tien, Nai-Wen Kim, Tahnbee and Kerschensteiner, Daniel 2016. Target-Specific Glycinergic Transmission from VGluT3-Expressing Amacrine Cells Shapes Suppressive Contrast Responses in the Retina. Cell Reports, Vol. 15, Issue. 7, p. 1369.

    Tatti, Roberta Bhaukaurally, Khaleel Gschwend, Olivier Seal, Rebecca P. Edwards, Robert H. Rodriguez, Ivan and Carleton, Alan 2014. A population of glomerular glutamatergic neurons controls sensory information transfer in the mouse olfactory bulb. Nature Communications, Vol. 5,

    Della Santina, Luca Kuo, Sidney P. Yoshimatsu, Takeshi Okawa, Haruhisa Suzuki, Sachihiro C. Hoon, Mrinalini Tsuboyama, Kotaro Rieke, Fred and Wong, Rachel O.L. 2016. Glutamatergic Monopolar Interneurons Provide a Novel Pathway of Excitation in the Mouse Retina. Current Biology, Vol. 26, Issue. 15, p. 2070.

    Peirs, Cedric Williams, Sean-Paul G. Zhao, Xinyi Walsh, Claire E. Gedeon, Jeremy Y. Cagle, Natalie E. Goldring, Adam C. Hioki, Hiroyuki Liu, Zheng Marell, Paulina S. and Seal, Rebecca P. 2015. Dorsal Horn Circuits for Persistent Mechanical Pain. Neuron, Vol. 87, Issue. 4, p. 797.

    Michalski, D. Härtig, W. Krügel, K. Edwards, R.H. Böddener, M. Böhme, L. Pannicke, T. Reichenbach, A. and Grosche, A. 2013. Region-specific expression of vesicular glutamate and GABA transporters under various ischaemic conditions in mouse forebrain and retina. Neuroscience, Vol. 231, p. 328.

    Honsek, Silke D. Seal, Rebecca P. and Sandkühler, Jürgen 2015. Presynaptic inhibition of optogenetically identified VGluT3+ sensory fibres by opioids and baclofen. PAIN, Vol. 156, Issue. 2, p. 243.

    Stafford, Benjamin K. Manookin, Michael B. Singer, Joshua H. and Demb, Jonathan B. 2014. NMDA and AMPA receptors contribute similarly to temporal processing in mammalian retinal ganglion cells. The Journal of Physiology, Vol. 592, Issue. 22, p. 4877.

    MARSHAK, DAVID W. CHUANG, ALICE Z. DOLINO, DREW M. JACOBY, ROY A. LIU, WEILEY S. LONG, YE SHERMAN, MICHAEL B. SUH, JAE M. VILA, ALEJANDRO and MILLS, STEPHEN L. 2015. Synaptic connections of amacrine cells containing vesicular glutamate transporter 3 in baboon retinas. Visual Neuroscience, Vol. 32,

    Qi, Jia Zhang, Shiliang Wang, Hui-Ling Wang, Huikun de Jesus Aceves Buendia, Jose Hoffman, Alexander F. Lupica, Carl R. Seal, Rebecca P. and Morales, Marisela 2014. A glutamatergic reward input from the dorsal raphe to ventral tegmental area dopamine neurons. Nature Communications, Vol. 5, p. 5390.

    Dhande, Onkar S. Stafford, Benjamin K. Lim, Jung-Hwan A. and Huberman, Andrew D. 2015. Contributions of Retinal Ganglion Cells to Subcortical Visual Processing and Behaviors. Annual Review of Vision Science, Vol. 1, Issue. 1, p. 291.

    Lee, Seunghoon Zhang, Yi Chen, Minggang and Zhou, Z. Jimmy 2016. Segregated Glycine-Glutamate Co-transmission from vGluT3 Amacrine Cells to Contrast-Suppressed and Contrast-Enhanced Retinal Circuits. Neuron, Vol. 90, Issue. 1, p. 27.

    Hoggarth, Alex McLaughlin, Amanda J. Ronellenfitch, Kara Trenholm, Stuart Vasandani, Rishi Sethuramanujam, Santhosh Schwab, David Briggman, Kevin L. and Awatramani, Gautam B. 2015. Specific Wiring of Distinct Amacrine Cells in the Directionally Selective Retinal Circuit Permits Independent Coding of Direction and Size. Neuron, Vol. 86, Issue. 1, p. 276.

    Lee, Seunghoon Chen, Lujing Chen, Minggang Ye, Meijun Seal, Rebecca P. and Zhou, Z. Jimmy 2014. An Unconventional Glutamatergic Circuit in the Retina Formed by vGluT3 Amacrine Cells. Neuron, Vol. 84, Issue. 4, p. 708.


Genetic targeting and physiological features of VGLUT3+ amacrine cells

  • DOI:
  • Published online: 25 August 2011

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.

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:
Linked references
Hide All

This list contains references from the content that can be linked to their source. For a full set of references and notes please see the PDF or HTML where available.

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.

Recommend this journal

Email your librarian or administrator to recommend adding this journal to your organisation's collection.

Visual Neuroscience
  • ISSN: 0952-5238
  • EISSN: 1469-8714
  • URL: /core/journals/visual-neuroscience
Please enter your name
Please enter a valid email address
Who would you like to send this to? *