Vesicular glutamate transport promotes dopamine storage and glutamate corelease in vivo
Open accessAbstract
Dopamine neurons in the ventral tegmental area (VTA) play an important role in the motivational systems underlying drug addiction, and recent work has suggested that they also release the excitatory neurotransmitter glutamate. To assess a physiological role for glutamate corelease, we disrupted the expression of vesicular glutamate transporter 2 selectively in dopamine neurons. The conditional knockout abolishes glutamate release from midbrain dopamine neurons in culture and severely reduces their excitatory synaptic output in mesoaccumbens slices. Baseline motor behavior is not affected, but stimulation of locomotor activity by cocaine is impaired, apparently through a selective reduction of dopamine stores in the projection of VTA neurons to ventral striatum. Glutamate co-entry promotes monoamine storage by increasing the pH gradient that drives vesicular monoamine transport. Remarkably, low concentrations of glutamate acidify synaptic vesicles more slowly but to a greater extent than equimolar Cl(-), indicating a distinct, presynaptic mechanism to regulate quantal size.
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Selective deletion of Slc17a6 from DA neurons decreases DA release in the ventral striatum.
“decreased DA release in the ventral striatum”
From Synaptic and circuit functions of multitransmitter neurons in the mammalian brain (2023) · cites this paper as [113]
Selective deletion of Slc17a6 from DA neurons in vivo abolishes glutamate release.
“selective deletion of Slc17a6 from DA neurons in vivo abolished glutamate release”
From Synaptic and circuit functions of multitransmitter neurons in the mammalian brain (2023) · cites this paper as [113]
vGluT2 can stimulate monoamine uptake into synaptic vesicles by vMAT2 by lowering intravesicular pH, providing a mechanism for reduced DA release when vGluT2 is absent.
“vGluT2 was capable of stimulating monoamine uptake into synaptic vesicles by vMAT2 by lowering the intravesicular pH, providing a mechanism for reduced DA release in the absence of vGluT2.113”
From Synaptic and circuit functions of multitransmitter neurons in the mammalian brain (2023) · cites this paper as [113]
Some cells in the SN and VTA are GABAergic or glutamatergic, and others release both glutamate and dopamine.
“Although the SN and VTA are known as dopaminergic regions, some cells in these regions are GABAergic or glutamatergic, and others release both glutamate and dopamine [31, 32].”
From A neoHebbian framework for episodic memory; role of dopamine-dependent late LTP (2011) · cites this paper as [32]
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Cre reporter strains produced by targeted insertion of EYFP and ECFP into the ROSA26 locus
Srinivas, S., Watanabe, T., Lin, C.-S., William, C. M., Tanabe, Y., Jessell, T. M., & Costantini, F. (2001) · BMC Developmental Biology · doi:10.1186/1471-213x-1-4 · Cited by 3,121 · see citing works
Visualizing secretion and synaptic transmission with pH-sensitive green fluorescent proteins
Miesenböck, G., Angelis, D. A. D., & Rothman, J. E. (1998) · Nature · doi:10.1038/28190 · Cited by 2,569 · see citing works
A gene expression atlas of the central nervous system based on bacterial artificial chromosomes
Gong, S., Zheng, C., Doughty, M. L., Losos, K., Didkovsky, N., Schambra, U. B., Nowak, N. J., Joyner, A., Leblanc, G., Hatten, M. E., et al. (2003) · Nature · doi:10.1038/nature02033 · Cited by 2,108 · see citing works
Ikemoto, S. (2007) · Brain Research Reviews · doi:10.1016/j.brainresrev.2007.05.004 · Cited by 1,477 · see citing works
Cell Biology: a Laboratory Handbook
Harris, A. (1995) · Journal of Medical Genetics · doi:10.1136/jmg.32.9.759 · Cited by 1,230 · see citing works
Cell biology :a laboratory handbook.
Celis, J. E. (1994) · Cited by 1,199 · see citing works
Plasma membrane monoamine transporters: structure, regulation and function
Torres, G. E., Gainetdinov, R. R., & Caron, M. G. (2003) · Nature reviews. Neuroscience · doi:10.1038/nrn1008 · Cited by 936 · see citing works
Takamori, S., Rhee, J. S., Rosenmund, C., & Jahn, R. (2000) · Nature · doi:10.1038/35025070 · Cited by 862 · see citing works
Novak, A., Guo, C., Yang, W., Nagy, A., & Lobe, C. G. (2000) · genesis · doi:10.1002/1526-968x(200011/12)28:3/4 · Cited by 841 · see citing works
Uptake of Glutamate into Synaptic Vesicles by an Inorganic Phosphate Transporter
Bellocchio, E. E., Reimer, R. J., Fremeau, R. T., & Edwards, R. H. (2000) · Science · doi:10.1126/science.289.5481.957 · Cited by 795 · see citing works
Self-citationCorelease of Two Fast Neurotransmitters at a Central Synapse
Jonas, P., Bischofberger, J., & Sandkühler, J. (1998) · Science · doi:10.1126/science.281.5375.419 · Cited by 784 · see citing works
Uniform Inhibition of Dopamine Neurons in the Ventral Tegmental Area by Aversive Stimuli
Ungless, M. A., Magill, P. J., & Bolam, J. P. (2004) · Science · doi:10.1126/science.1093360 · Cited by 782 · see citing works
VGLUTs define subsets of excitatory neurons and suggest novel roles for glutamate
Fremeau, R. T., Voglmaier, S., Seal, R. P., & Edwards, R. H. (2004) · Trends in Neurosciences · doi:10.1016/j.tins.2003.11.005 · Cited by 745 · see citing works
Self-citationSchuldiner, S., Rottenberg, H., & Avron, M. (1972) · European Journal of Biochemistry · doi:10.1111/j.1432-1033.1972.tb01667.x · Cited by 650 · see citing works
A third vesicular glutamate transporter expressed by cholinergic and serotoninergic neurons
Gras, C., Herzog, E., Bellenchi, G. C., Bernard, V., Ravassard, P., Pohl, M., Gasnier, B., Giros, B., & El Mestikawy, S. (2002) · The Journal of Neuroscience · doi:10.1523/jneurosci.22-13-05442.2002 · Cited by 639 · see citing works
Secondary active transport mediated by a prokaryotic homologue of ClC Cl- channels
Accardi, A., & Miller, C. (2004) · Nature · doi:10.1038/nature02314 · Cited by 612 · see citing works
The Use of pHluorins for Optical Measurements of Presynaptic Activity
Sankaranarayanan, S., Angelis, D. A. D., Rothman, J. E., & Ryan, T. A. (2000) · Biophysical Journal · doi:10.1016/s0006-3495(00)76468-x · Cited by 586 · see citing works
Fremeau, R. T., Burman, J. L., Qureshi, T., Tran, C. H., Proctor, J. M., Johnson, J., Zhang, H., Sulzer, D. L., Copenhagen, D. R., Storm‐Mathisen, J., et al. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.222546799 · Cited by 568 · see citing works
Self-citationMargolis, E. B., Lock, H., Hjelmstad, G. O., & Fields, H. L. (2006) · The Journal of Physiology · doi:10.1113/jphysiol.2006.117069 · Cited by 527 · see citing works
Glutamatergic Afferents of the Ventral Tegmental Area in the Rat
Geisler, S., Derst, C., Veh, R. W., & Zahm, D. S. (2007) · Journal of Neuroscience · doi:10.1523/jneurosci.0012-07.2007 · Cited by 486 · see citing works
Voltage-dependent electrogenic chloride/proton exchange by endosomal CLC proteins
Scheel, O., Zdebik, A., Lourdel, S., & Jentsch, T. (2005) · Nature · doi:10.1038/nature03860 · Cited by 483 · see citing works
Parkin-deficient mice are not a robust model of parkinsonism
Perez, F. A., & Palmiter, R. D. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0409598102 · Cited by 477 · see citing works
Self-citationChloride/proton antiporter activity of mammalian CLC proteins ClC-4 and ClC-5
Picollo, A., & Pusch, M. (2005) · Nature · doi:10.1038/nature03720 · Cited by 454 · see citing works
Characterization of Glutamate Uptake into Synaptic Vesicles
Naito, S., & Ueda, T. (1985) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.1985.tb07118.x · Cited by 446 · see citing works
Schäfer, M. K.-H., Varoqui, H., Defamie, N., Weihe, E., & Erickson, J. D. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m206738200 · Cited by 410 · see citing works
The Cl-/H+ antiporter ClC-7 is the primary chloride permeation pathway in lysosomes
Graves, A. R., Curran, P. K., Smith, C. L., & Mindell, J. A. (2008) · Nature · doi:10.1038/nature06907 · Cited by 399 · see citing works
A shared vesicular carrier allows synaptic corelease of GABA and glycine
Wojcik, S. M., Katsurabayashi, S., Guillemin, I., Friauf, E., Rosenmund, C., Brose, N., & Rhee, J.-S. (2006) · Neuron · doi:10.1016/j.neuron.2006.04.016 · Cited by 374 · see citing works
Glutamatergic neurons are present in the rat ventral tegmental area
Yamaguchi, T., Sheen, W., & Morales, M. (2007) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2006.05263.x · Cited by 367 · see citing works
Maycox, P. R., Deckwerth, T. L., Hell, J. W., & Jahn, R. (1988) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)37605-7 · Cited by 361 · see citing works
Fon, E. A., Pothos, E. N., Sun, B.-C., Killeen, N. P., Sulzer, D. L., & Edwards, R. H. (1997) · Neuron · doi:10.1016/s0896-6273(00)80418-3 · Cited by 337 · see citing works
Self-citationControl of dopamine extracellular concentration in rat striatum by impulse flow and uptake
Wightman, R. M., & Zimmerman, J. B. (1990) · Brain Research Reviews · doi:10.1016/0165-0173(90)90015-g · Cited by 328 · see citing works
Johnson, R. G. (1988) · Physiological Reviews · doi:10.1152/physrev.1988.68.1.232 · Cited by 323 · see citing works
Dopamine neurons make glutamatergic synapses in vitro
Sulzer, D. L., Joyce, M. P., Lin, L., Geldwert, D., Haber, S. N., Hattori, T., & Rayport, S. (1998) · PubMed Central · doi:10.7916/d8-snm4-r132 · Cited by 316 · see citing works
Self-citationTargeted gene expression in dopamine and serotonin neurons of the mouse brain
Zhuang, X., Masson, J., Gingrich, J. A., Rayport, S., & Hen, R. (2004) · Journal of Neuroscience Methods · doi:10.1016/j.jneumeth.2004.09.020 · Cited by 316 · see citing works
Self-citationDopamine Neurons Make Glutamatergic SynapsesIn Vitro
Sulzer, D. L., Joyce, M. P., Lin, L., Geldwert, D., Haber, S. N., Hattori, T., & Rayport, S. (1998) · Journal of Neuroscience · doi:10.1523/jneurosci.18-12-04588.1998 · Cited by 304 · see citing works
Self-citationVGLUTs: ‘Exciting’ times for glutamatergic research?
Takamori, S. (2006) · Neuroscience Research · doi:10.1016/j.neures.2006.04.016 · Cited by 249 · see citing works
Spyraki, C., Fibiger, H. C., & Phillips, A. G. (1982) · Brain Research · doi:10.1016/0006-8993(82)90686-2 · Cited by 242 · see citing works
Stornetta, R. L., Sevigny, C. P., & Guyenet, P. G. (2002) · The Journal of Comparative Neurology · doi:10.1002/cne.10141 · Cited by 236 · see citing works
Mesocortical Dopamine Neurons Operate in Distinct Temporal Domains Using Multimodal Signaling
Lavin, A., Nogueira, L., Lapish, C. C., Wightman, R. M., Phillips, P. E. M., & Seamans, J. K. (2005) · The Journal of Neuroscience · doi:10.1523/jneurosci.0557-05.2005 · Cited by 233 · see citing works
Kawano, M., Kawasaki, A., Sakata‐Haga, H., Fukui, Y., Kawano, H., Nogami, H., & Hisano, S. (2006) · The Journal of Comparative Neurology · doi:10.1002/cne.21054 · Cited by 230 · see citing works
Developmental switch from GABA to glycine release in single central synaptic terminals
Nabekura, J., Katsurabayashi, S., Kakazu, Y., Shibata, S., Matsubara, A., Jinno, S., Mizoguchi, Y., Sasaki, A., & Ishibashi, H. (2004) · Nature Neuroscience · doi:10.1038/nn1170 · Cited by 228 · see citing works
Dopamine Neurons Mediate a Fast Excitatory Signal via Their Glutamatergic Synapses
Chuhma, N., Zhang, H., Masson, J., Zhuang, X., Sulzer, D. L., Hen, R., & Rayport, S. (2004) · Journal of Neuroscience · doi:10.1523/jneurosci.4317-03.2004 · Cited by 228 · see citing works
Self-citationPHYSIOLOGICAL FUNCTIONS OF CLC Cl−CHANNELS GLEANED FROM HUMAN GENETIC DISEASE AND MOUSE MODELS
Jentsch, T. J., Poët, M., Fuhrmann, J. C., & Zdebik, A. A. (2005) · Annual Review of Physiology · doi:10.1146/annurev.physiol.67.032003.153245 · Cited by 227 · see citing works
Vesicular Glutamate Transporter VGLUT2 Expression Levels Control Quantal Size and Neuropathic Pain
Moechars, D., Weston, M. C., Leo, S., Callaerts‐Vegh, Z., Goris, I., Daneels, G., Buist, A., Cik, M., van der Spek, P. J., Kass, S. U., et al. (2006) · Journal of Neuroscience · doi:10.1523/jneurosci.2556-06.2006 · Cited by 226 · see citing works
Cocaine, reward, movement and monoamine transporters
Uhl, G. R., Hall, F. S., & Sora, I. (2002) · Molecular Psychiatry · doi:10.1038/sj.mp.4000964 · Cited by 219 · see citing works
The vesicular glutamate transporter VGLUT3 synergizes striatal acetylcholine tone
Gras, C., Amilhon, B., Lepicard, È. M., Poirel, O., Vinatier, J., Herbin, M., Dumas, S., Tzavara, E. T., Wade, M. R., Nomikos, G. G., et al. (2008) · Nature Neuroscience · doi:10.1038/nn2052 · Cited by 211 · see citing works
Wallén‐Mackenzie, Å., Gezelius, H., Thoby‐Brisson, M., Nygård, A., Enjin, A., Fujiyama, F., Fortin, G., & Kullander, K. (2006) · Journal of Neuroscience · doi:10.1523/jneurosci.3855-06.2006 · Cited by 198 · see citing works
Protonmotive force and catecholamine transport in isolated chromaffin granules.
Johnson, R. G., & Scarpa, A. (1979) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)50650-5 · Cited by 193 · see citing works
Corelease of Dopamine and Serotonin from Striatal Dopamine Terminals
Zhou, F.-M., Liang, Y., Salas, R., Zhang, L., Biasi, M. D., & Dani, J. A. (2005) · Neuron · doi:10.1016/j.neuron.2005.02.010 · Cited by 187 · see citing works
Tabb, J. S., Kish, P. E., Van Dyke, R., & Ueda, T. (1992) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)49549-5 · Cited by 182 · see citing works
Organic anion transport is the primary function of the SLC17/type I phosphate transporter family
Reimer, R. J., & Edwards, R. H. (2004) · Pflügers Archiv - European Journal of Physiology · doi:10.1007/s00424-003-1087-y · Cited by 181 · see citing works
Self-citationCaMKII?-cre transgene expression and recombination patterns in the mouse brain
Dragatsis, I., & Zeitlin, S. O. (2000) · genesis · doi:10.1002/(sici)1526-968x(200002)26:2 · Cited by 171 · see citing works
Bo, G. D., St-Gelais, F., Danik, M., Williams, S., Cotton, M., & Trudeau, L. (2004) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.2003.02277.x · Cited by 159 · see citing works
A chloride conductance in VGLUT1 underlies maximal glutamate loading into synaptic vesicles
Schenck, S., Wojcik, S. M., Brose, N., & Takamori, S. (2009) · Nature Neuroscience · doi:10.1038/nn.2248 · Cited by 155 · see citing works
Busch, A. E., Schuster, A., Waldegger, S., Wagner, C. A., Zempel, G., Bröer, S., Biber, J., Murer, H., & Lang, F. J. W. (1996) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.93.11.5347 · Cited by 142 · see citing works
Price, G. D., & Trussell, L. O. (2006) · Journal of Neuroscience · doi:10.1523/jneurosci.1660-06.2006 · Cited by 141 · see citing works
Staggered development of GABAergic and glycinergic transmission in the MNTB
Awatramani, G. B., Turecek, R., & Trussell, L. O. (2005) · Journal of Neurophysiology · doi:10.1152/jn.00798.2004 · Cited by 138 · see citing works
Synaptic glutamate release by postnatal rat serotonergic neurons in microculture
Johnson, M. D. (1994) · Neuron · doi:10.1016/0896-6273(94)90283-6 · Cited by 137 · see citing works
Regulation of Glutamate Transport into Synaptic Vesicles by Chloride and Proton Gradient
Wolosker, H., Souza, D. O., & MEIS, L. D. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.20.11726 · Cited by 137 · see citing works
Characterization of a H+-ATPase in rat brain synaptic vesicles
Cidon, S., & Sihra, T. S. (1989) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)83180-5 · Cited by 135 · see citing works
Glutamate in dopamine neurons: Synaptic versus diffuse transmission
Descarries, L., Bérubé‐Carrière, N., Riad, M., Bo, G. D., Méndez, J. A. T., & Trudeau, L. (2007) · Brain Research Reviews · doi:10.1016/j.brainresrev.2007.10.005 · Cited by 128 · see citing works
Zhang, H., & Sulzer, D. L. (2003) · Journal of Neuroscience · doi:10.1523/jneurosci.23-33-10585.2003 · Cited by 124 · see citing works
Self-citationOmelchenko, N., & Sesack, S. R. (2007) · Neuroscience · doi:10.1016/j.neuroscience.2007.02.016 · Cited by 121 · see citing works
An anion binding site that regulates the glutamate transporter of synaptic vesicles.
Hartinger, J., & Jahn, R. (1993) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)49435-0 · Cited by 120 · see citing works
Méndez, J. A. T., Bourque, M.-J., Bo, G. D., Bourdeau, M. L., Danik, M., Williams, S., Lacaille, J., & Trudeau, L. (2008) · Journal of Neuroscience · doi:10.1523/jneurosci.1331-08.2008 · Cited by 108 · see citing works
Gutiérrez, R. (2000) · Journal of Neurophysiology · doi:10.1152/jn.2000.84.6.3088 · Cited by 103 · see citing works
Cocaine-Conditioned Place Preference by Dopamine-Deficient Mice Is Mediated by Serotonin
Hnasko, T. S., Sotak, B. N., & Palmiter, R. D. (2007) · The Journal of Neuroscience · doi:10.1523/jneurosci.3133-07.2007 · Cited by 99 · see citing works
Self-citationThe dual dopamine‐glutamate phenotype of growing mesencephalic neurons regresses in mature rat brain
Bérubé‐Carrière, N., Riad, M., Bo, G. D., Lévesque, D., Trudeau, L., & Descarries, L. (2009) · The Journal of Comparative Neurology · doi:10.1002/cne.22194 · Cited by 98 · see citing works
Mesoaccumbens dopamine neuron synapses reconstructed in vitro are glutamatergic
Joyce, M. P., & Rayport, S. (2000) · Neuroscience · doi:10.1016/s0306-4522(00)00219-0 · Cited by 86 · see citing works
Self-citationBo, G. D., Bérubé‐Carrière, N., Méndez, J. A. T., Leo, D., Riad, M., Descarries, L., Lévesque, D., & Trudeau, L. (2008) · Neuroscience · doi:10.1016/j.neuroscience.2008.07.032 · Cited by 86 · see citing works
Chuhma, N., Choi, W., Mingote, S., & Rayport, S. (2009) · Neuroscience · doi:10.1016/j.neuroscience.2009.08.057 · Cited by 83 · see citing works
Self-citationCharacterization of ATP Transport into Chromaffin Granule Ghosts
Bankston, L. A., & Guidotti, G. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.29.17132 · Cited by 83 · see citing works
Fujiyama, F., Unzai, T., Nakamura, K., Nomura, S., & Kaneko, T. (2006) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2006.05177.x · Cited by 81 · see citing works
Nguyen, M. L., Cox, G. D., & Parsons, S. M. (1998) · Biochemistry · doi:10.1021/bi9802263 · Cited by 66 · see citing works
Bröer, S., Schuster, A., Wagner, C. A., et al. (1998) · The Journal of Membrane Biology · doi:10.1007/s002329900394 · Cited by 62 · see citing works
Syntaxin-1A Is Excluded from Recycling Synaptic Vesicles at Nerve Terminals
Mitchell, S. J., & Ryan, T. A. (2004) · Journal of Neuroscience · doi:10.1523/jneurosci.0174-04.2004 · Cited by 57 · see citing works
Erickson, J. D., Masserano, J. M., Barnes, E. M., Ruth, J. A., & Weiner, N. (1990) · Brain Research · doi:10.1016/0006-8993(90)90912-u · Cited by 35 · see citing works
Coupling of H+ Gradients to Catecholamine Transport in Chromaffin Granulesa
Johnson, R. G., Carty, S. E., & Scarpa, A. (1985) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.1985.tb14874.x · Cited by 18 · see citing works
Preparation of Synaptic Vesicles from Mammalian Brain
Hell, J. W., & Jahn, R. (2006) · Cell Biology · doi:10.1016/b978-012164730-8/50084-8 · Cited by 16 · see citing works
POIRIER, L. J. (1975) · Journal of Neural Transmission · doi:10.1007/bf01670129 · Cited by 16 · see citing works
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Bromberg-Martin, E. S., Matsumoto, M., & Hikosaka, O. (2010) · Neuron · doi:10.1016/j.neuron.2010.11.022 · Cited by 2,396 · see citing works
Ventral tegmental area: cellular heterogeneity, connectivity and behaviour
Morales, M., & Margolis, E. B. (2017) · Nature reviews. Neuroscience · doi:10.1038/nrn.2016.165 · Cited by 1,108 · see citing works
Reward and aversion in a heterogeneous midbrain dopamine system
Lammel, S., Lim, B. K., & Malenka, R. C. (2014) · Neuropharmacology · doi:10.1016/j.neuropharm.2013.03.019 · Cited by 804 · see citing works
Dopaminergic modulation of synaptic transmission in cortex and striatum
Tritsch, N. X., & Sabatini, B. L. (2012) · Neuron · doi:10.1016/j.neuron.2012.09.023 · Cited by 756 · see citing works
Scofield, M. D., Heinsbroek, J. A., Gipson, C. D., Kupchik, Y. M., Spencer, S., Smith, A. C. W., Roberts-Wolfe, D., & Kalivas, P. W. (2016) · Pharmacological Reviews · doi:10.1124/pr.116.012484 · Cited by 598 · see citing works
Dopaminergic neurons inhibit striatal output through non-canonical release of GABA
Tritsch, N. X., Ding, J. B., & Sabatini, B. L. (2012) · Nature · doi:10.1038/nature11466 · Cited by 576 · see citing works
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Stuber, G. D., Hnasko, T. S., Britt, J. P., Edwards, R. H., & Bonci, A. (2010) · Journal of Neuroscience · doi:10.1523/jneurosci.1754-10.2010 · Cited by 529 · see citing works
Self-citationA neoHebbian framework for episodic memory; role of dopamine-dependent late LTP
Lisman, J., Grace, A. A., & Duzel, E. (2011) · Trends in Neurosciences · doi:10.1016/j.tins.2011.07.006 · Cited by 465 · see citing works
Striatal dopamine neurotransmission: Regulation of release and uptake
Sulzer, D., Cragg, S. J., & Rice, M. E. (2016) · Basal Ganglia · doi:10.1016/j.baga.2016.02.001 · Cited by 382 · see citing works
Self-citationFrom glutamate co-release to vesicular synergy: vesicular glutamate transporters
El Mestikawy, S., Wallén-Mackenzie, Å., Fortin, G. M., Descarries, L., & Trudeau, L.-E. (2011) · Nature Reviews Neuroscience · doi:10.1038/nrn2969 · Cited by 385 · see citing works
Adamantidis, A. R., Tsai, H.-C., Boutrel, B., Zhang, F., Stuber, G. D., Budygin, E. A., Tourino, C., Bonci, A., Deisseroth, K., & de Lecea, L. (2011) · Journal of Neuroscience · doi:10.1523/jneurosci.2246-11.2011 · Cited by 357 · see citing works
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Ren, J., Qin, C., Hu, F., Tan, J., Qiu, L., Zhao, S., Feng, G., & Luo, M. (2011) · Neuron · doi:10.1016/j.neuron.2010.12.038 · Cited by 315 · see citing works
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Hnasko, T. S., & Edwards, R. H. (2012) · Annual Review of Physiology · doi:10.1146/annurev-physiol-020911-153315 · Cited by 284 · see citing works
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Poulin, J.-F., Gaertner, Z., Moreno-Ramos, O. A., & Awatramani, R. (2020) · Trends in Neurosciences · doi:10.1016/j.tins.2020.01.004 · Cited by 238 · see citing works
Aldehyde dehydrogenase 1a1 mediates a GABA synthesis pathway in midbrain dopaminergic neurons
Kim, J.-I., Ganesan, S., Luo, S. X., Wu, Y.-W., Park, E., Huang, E. J., Chen, L., & Ding, J. B. (2015) · Science · doi:10.1126/science.aac4690 · Cited by 217 · see citing works
Chuhma, N., Mingote, S., Moore, H., & Rayport, S. (2014) · Neuron · doi:10.1016/j.neuron.2013.12.027 · Cited by 233 · see citing works
Self-citationA Neural Circuit for the Suppression of Pain by a Competing Need State
Alhadeff, A. L., Su, Z., Hernandez, E., Klima, M. L., Phillips, S. Z., Holland, R. A., Guo, C., Hantman, A. W., De Jonghe, B. C., & Betley, J. N. (2018) · Cell · doi:10.1016/j.cell.2018.02.057 · Cited by 218 · see citing works
Glutamate neurons within the midbrain dopamine regions
Morales, M., & Root, D. H. (2014) · Neuroscience · doi:10.1016/j.neuroscience.2014.05.032 · Cited by 218 · see citing works
Li, C., Sugam, J. A., Lowery-Gionta, E. G., McElligott, Z. A., McCall, N. M., Lopez, A. J., McKlveen, J. M., Pleil, K. E., & Kash, T. L. (2016) · Neuropsychopharmacology · doi:10.1038/npp.2016.12 · Cited by 161 · see citing works
Learning from Action: Reconsidering Movement Signaling in Midbrain Dopamine Neuron Activity
Coddington, L. T., & Dudman, J. T. (2019) · Neuron · doi:10.1016/j.neuron.2019.08.036 · Cited by 150 · see citing works
Neuropeptide and small transmitter coexistence: Fundamental studies and relevance to mental illness
Hökfelt, T., Barde, S., Xu, Z.-Q. D., Kuteeva, E., Rüegg, J., Le Maitre, E., Risling, M., Kehr, J., Ihnatko, R., Theodorsson, E., et al. (2018) · Frontiers in Neural Circuits · doi:10.3389/fncir.2018.00106 · Cited by 139 · see citing works
Vesicular Neurotransmitter Transporter: Bioenergetics and Regulation of Glutamate Transport
Omote, H., Miyaji, T., Juge, N., & Moriyama, Y. (2011) · Biochemistry · doi:10.1021/bi200567k · Cited by 112 · see citing works
Zhang, T. A., Placzek, A. N., & Dani, J. A. (2010) · Neuropharmacology · doi:10.1016/j.neuropharm.2010.06.004 · Cited by 100 · see citing works
An essential role of acetylcholine-glutamate synergy at habenular synapses in nicotine dependence
Frahm, S., Antolin-Fontes, B., Görlich, A., Zander, J.-F., Ahnert-Hilger, G., & Ibañez-Tallon, I. (2015) · eLife · doi:10.7554/elife.11396 · Cited by 98 · see citing works
Striatal cholinergic neurotransmission requires VGLUT3
Nelson, A. B., Bussert, T. G., Kreitzer, A. C., & Seal, R. P. (2014) · Journal of Neuroscience · doi:10.1523/jneurosci.0901-14.2014 · Cited by 99 · see citing works
Role for VGLUT2 in selective vulnerability of midbrain dopamine neurons
Steinkellner, T., Zell, V., Farino, Z. J., Sonders, M. S., Villeneuve, M., Freyberg, R. J., Przedborski, S., Lu, W., Freyberg, Z., & Hnasko, T. S. (2018) · Journal of Clinical Investigation · doi:10.1172/jci95795 · Cited by 102 · see citing works
Self-citationGorelova, N., Mulholland, P. J., Chandler, L. J., & Seamans, J. K. (2012) · Cerebral Cortex · doi:10.1093/cercor/bhr107 · Cited by 98 · see citing works
Mesolimbic Dopamine Transients in Motivated Behaviors: Focus on Maternal Behavior
Robinson, D. L., Zitzman, D. L., & Williams, S. K. (2011) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2011.00023 · Cited by 89 · see citing works
Wood, J., & Ahmari, S. E. (2015) · Frontiers in Systems Neuroscience · doi:10.3389/fnsys.2015.00171 · Cited by 85 · see citing works
“In recent years, it has come to light that VTA also contains a sizeable population of neurons that release glutamate, and that dopamine neurons can co-release glutamate and GABA (Yamaguchi et al., 2007, 2011; Hnasko et al., 2010; Stuber et al., 2010; Tritsch et al., 2012).”
BackgroundCocaine self-administration behaviors in ClockΔ19 mice
Ozburn, A. R., Larson, E. B., Self, D. W., & McClung, C. A. (2012) · Psychopharmacology · doi:10.1007/s00213-012-2704-2 · Cited by 85 · see citing works
Upmanyu, N., Jin, J., Emde, H. V. D., Ganzella, M., Bösche, L., Malviya, V. N., Zhuleku, E., Politi, A. Z., Ninov, M., Silbern, I., et al. (2022) · Neuron · doi:10.1016/j.neuron.2022.02.008 · Cited by 69 · see citing works
Synaptic and circuit functions of multitransmitter neurons in the mammalian brain
Wallace, M. L., & Sabatini, B. L. (2023) · Neuron · doi:10.1016/j.neuron.2023.06.003 · Cited by 59 · see citing works
Shen, H., Marino, R. A. M., McDevitt, R. A., Bi, G.-H., Chen, K., Madeo, G., Lee, P.-T., Liang, Y., De Biase, L. M., Su, T.-P., et al. (2018) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1800886115 · Cited by 58 · see citing works
Inhibitory co-transmission from midbrain dopamine neurons relies on presynaptic GABA uptake
Melani, R., & Tritsch, N. X. (2022) · Cell Reports · doi:10.1016/j.celrep.2022.110716 · Cited by 56 · see citing works
Paradoxical network excitation by glutamate release from VGluT3+ GABAergic interneurons
Pelkey, K. A., Calvigioni, D., Fang, C., Vargish, G., Ekins, T., Auville, K., Wester, J. C., Lai, M., Mackenzie-Gray Scott, C., Yuan, X., et al. (2020) · eLife · doi:10.7554/elife.51996 · Cited by 46 · see citing works
Divergent properties and independent regulation of striatal dopamine and GABA co-transmission
Zych, S. M., & Ford, C. P. (2022) · Cell Reports · doi:10.1016/j.celrep.2022.110823 · Cited by 46 · see citing works
Viereckel, T., Dumas, S., Smith-Anttila, C. J. A., Vlcek, B., Bimpisidis, Z., Lagerström, M. C., Konradsson-Geuken, Å., & Wallén-Mackenzie, Å. (2016) · Scientific Reports · doi:10.1038/srep35203 · Cited by 45 · see citing works
Fortin, G. M., Ducrot, C., Giguère, N., Kouwenhoven, W. M., Bourque, M.-J., Pacelli, C., Varaschin, R. K., Brill, M., Singh, S., Wiseman, P. W., et al. (2019) · The FASEB Journal · doi:10.1096/fj.201800713rr · Cited by 45 · see citing works
Khan, S., Stott, S. R. W., Chabrat, A., Truckenbrodt, A. M., Spencer-Dene, B., Nave, K.-A., Guillemot, F., Levesque, M., & Ang, S.-L. (2017) · The Journal of Neuroscience · doi:10.1523/jneurosci.2414-16.2016 · Cited by 37 · see citing works
Perelmuter, J. T., & Forlano, P. M. (2017) · Journal of Comparative Neurology · doi:10.1002/cne.24177 · Cited by 21 · see citing works
Analytical approaches to examine gamma-aminobutyric acid and glutamate vesicular co-packaging
Kim, S., & Sabatini, B. L. (2023) · Frontiers in Synaptic Neuroscience · doi:10.3389/fnsyn.2022.1076616 · Cited by 10 · see citing works
Vrettou, M., Thalhammer, S. B., Svensson, A.-L., Dumas, S., Nilsson, K. W., Wallén-Mackenzie, Å., Fredriksson, R., Nylander, I., & Comasco, E. (2023) · Drug and Alcohol Dependence Reports · doi:10.1016/j.dadr.2023.100180 · Cited by 4 · see citing works
- Authors
- Hnasko, T. S., Chuhma, N., Zhang, H., Goh, G. Y., Sulzer, D., Palmiter, R. D., Rayport, S., & Edwards, R. H.
- Affiliations
- University of California, San Francisco (US)
- New York State Psychiatric Institute (US)
- Columbia University Irving Medical Center (US)
- Howard Hughes Medical Institute (US)
- Corresponding author
- Edwards, Robert H.
- ORCID
- Venue
- Neuron
- Publisher
- Elsevier BV
- Published
- 2010-03
- Volume
- 65
- Issue
- 5
- Pages
- 643-656
- ISSN
- 0896-6273 (ISSN-L)
- PMC
- PMC2846457
- OpenAlex
- W2037500812
- Cited by
- 405
- References
- 80
- Citations by year
- 2026: 12 · 2025: 19 · 2024: 26 · 2023: 21 · 2022: 21 · 2021: 28 · 2020: 20 · 2019: 19 · 2018: 28 · 2017: 30 · 2016: 30 · 2015: 37 · 2014: 35 · 2013: 20 · 2012: 15
- FWCI
- 10.22
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (vor, 1270 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- Neuron (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Development Administration
- National Institute of Mental Health
- A.P. Giannini Foundation
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Keywords
- vesicular glutamate transporter 2, dopamine storage, ventral tegmental area, dopaminergic neurons, conditional knockout, quantal size, monoamine storage, ventral striatum
- MeSH terms
- Adenosine Triphosphate, Analysis of Variance, Animals, Animals, Newborn, Catecholamines, Cell Line, Transformed, Chlorides, Choline, Cocaine, Corpus Striatum, Dopamine, Humans, Hydrogen-Ion Concentration, Luminescent Proteins, Membrane Potentials, Mice, Transgenic, Motor Activity, Neurons, Serotonin, Synaptic Vesicles, Transfection, Tyrosine 3-Monooxygenase, Presynaptic Terminals, Glutamic Acid, Dopamine Uptake Inhibitors, Green Fluorescent Proteins, Vesicular Glutamate Transport Protein 2, Mice, Rats, In Vitro Techniques
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