Mesocorticolimbic Glutamatergic Pathway
Open accessAbstract
The mesocorticolimbic dopamine (DA) system plays important roles in reward, motivation, learning, memory, and movement. This system arises from the A10 region, comprising the ventral tegmental area and three adjacent midline nuclei (caudal linear nucleus, interfascicular nucleus, and rostral linear nucleus of the raphe). DAergic and GABAergic neurons are intermingled in this region with recently discovered glutamatergic neurons expressing the vesicular glutamate transporter 2 (VGluT2). Here, we show by in situ hybridization and immunohistochemistry that there are two subpopulations of neurons expressing VGluT2 mRNA in the A10 region: (1) a major subpopulation that expresses VGluT2 but lacks tyrosine hydroxylase (TH; VGluT2-only neurons), present in each nucleus of the A10 region, and (2) a smaller subpopulation that coexpresses VGluT2 and TH (VGluT2-TH neurons). By quantitative real-time PCR, we determined the mRNA copy numbers encoding VGluT2 or TH in samples of individual microdissected TH immunoreactive (IR) neurons. Data from both in situ hybridization and from mRNA quantification showed that VGluT2 mRNA is not present in every TH-IR neuron, but restricted to a subset of TH-IR neurons located in the medial portion of the A10 region. By integration of tract tracing, in situ hybridization, and immunohistochemistry, we found that VGluT2-only neurons and VGluT2-TH neurons each innervate both the prefrontal cortex and the nucleus accumbens. These findings establish that in addition to the well-recognized mesocorticolimbic DA-only and GABA-only pathways, there exist parallel mesocorticolimbic glutamate-only and glutamate-DA pathways.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Some dopaminergic neurons projecting to the various PFC subdomains are capable of co-releasing glutamate and have an exclusive excitatory effect on the GABAergic interneurons in the various layers of the PFC.
“Of note here is that some of these dopaminergic neurons projecting to the various PFC subdomains are capable of co-releasing glutamate as well and have an exclusive excitatory effect on the GABAergic interneurons in the various layers of the PFC [170–173].”
From Development of prefrontal cortex (2022) · cites this paper as [170]
The Results section (‘The PFC and the nAcc receive inputs…’; page unavailable) identifies PFC-projecting neurons that coexpress VGluT2 mRNA and TH, supporting a population with glutamatergic and dopaminergic markers. The paper does not establish glutamate co-release from those neurons or show that they exclusively excite GABAergic interneurons across PFC layers or subdomains. (LLM, conf=0.87)
Experimental — accuracy not yet measuredVarious sources of glutamatergic input projections include a subset of (non-)dopaminergic VTA neurons to GABAergic interneurons in the PFC.
“There are various sources of glutamatergic input projections including a subset of (non-)dopaminergic VTA neurons to GABAergic interneurons in the PFC [170–173].”
From Development of prefrontal cortex (2022) · cites this paper as [170]
The section ‘The PFC and the nAcc receive inputs from VGluT2-only neurons and from VGluT2-TH neurons’ (page unavailable) identifies glutamatergic PFC-projecting neurons both without and with the dopamine marker TH. It does not identify GABAergic interneurons as the targets within the PFC, so that specificity is unsupported. (LLM, conf=0.88)
Experimental — accuracy not yet measured
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
The Rat Brain in Stereotaxic Coordinates
Paxinos, G., & Watson, C. (1983) · Elsevier eBooks · doi:10.1016/c2009-0-63235-9 · Cited by 28,585 · see citing works
Swanson, L. W. (1982) · Brain Research Bulletin · doi:10.1016/0361-9230(82)90145-9 · Cited by 1,718 · see citing works
Opioids excite dopamine neurons by hyperpolarization of local interneurons
Johnson, S., & North, R. (1992) · The Journal of Neuroscience · doi:10.1523/jneurosci.12-02-00483.1992 · Cited by 1,637 · see citing works
Matsuda, W., Furuta, T., Nakamura, K. C., Hioki, H., Fujiyama, F., Arai, R., & Kaneko, T. (2009) · The Journal of Neuroscience · doi:10.1523/jneurosci.4029-08.2009 · Cited by 865 · see citing works
Nair‐Roberts, R. G., Chatelain-Badie, S. D., Benson, E. M., White‐Cooper, H., Bolam, J. P., & Ungless, M. A. (2008) · Neuroscience · doi:10.1016/j.neuroscience.2008.01.046 · Cited by 653 · see citing works
Dopaminergic terminals in the nucleus accumbens but not the dorsal striatum corelease glutamate
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
Vesicular glutamate transport promotes dopamine storage and glutamate corelease in vivo
Hnasko, T. S., Chuhma, N., Zhang, H., Goh, G. Y., Sulzer, D., Palmiter, R. D., Rayport, S., & Edwards, R. H. (2010) · Neuron · doi:10.1016/j.neuron.2010.02.012 · Cited by 405 · 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
Self-citationGABA-containing neurons in the ventral tegmental area project to the nucleus accumbens in rat brain
Bockstaele, E. J. V., & Pickel, V. M. (1995) · Brain Research · doi:10.1016/0006-8993(95)00334-m · Cited by 328 · see citing works
Voorn, P., Jorritsma‐Byham, B., Dijk, C. V., & Buijs, R. M. (1986) · The Journal of Comparative Neurology · doi:10.1002/cne.902510106 · Cited by 318 · 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
Glutamatergic signaling by mesolimbic dopamine neurons in the nucleus accumbens
Tecuapetla, F., Patel, J. C., Xenias, H., English, D., Tadros, I., Shah, F., Berlin, J., Deisseroth, K., Rice, M. E., Tepper, J. M., et al. (2010) · The Journal of Neuroscience · doi:10.1523/jneurosci.0265-10.2010 · Cited by 310 · see citing works
Hur, E. E., & Záborszky, L. (2005) · The Journal of Comparative Neurology · doi:10.1002/cne.20444 · Cited by 305 · see citing works
Dobi, A., Margolis, E. B., Wang, H.-L., Harvey, B. K., & Morales, M. (2010) · The Journal of Neuroscience · doi:10.1523/jneurosci.3884-09.2010 · Cited by 257 · see citing works
Self-citationMidbrain dopaminergic neurons (nuclei A8, A9, and A10): Three‐dimensional reconstruction in the rat
German, D. C., & Manaye, K. F. (1993) · The Journal of Comparative Neurology · doi:10.1002/cne.903310302 · Cited by 255 · 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
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
Omelchenko, N., & Sesack, S. R. (2009) · Synapse · doi:10.1002/syn.20668 · Cited by 194 · see citing works
The cytoarchitecture of the interfascicular nucleus and ventral tegmental area of tsai in the rat
Phillipson, O. T. (1979) · The Journal of Comparative Neurology · doi:10.1002/cne.901870106 · Cited by 193 · see citing works
Morales, M., & Wang, S. (2002) · Journal of Neuroscience · doi:10.1523/jneurosci.22-15-06732.2002 · Cited by 175 · see citing works
Self-citationArluison, M., Dietl, M., & Thibault, J. (1984) · Brain Research Bulletin · doi:10.1016/0361-9230(84)90128-x · Cited by 173 · see citing works
GDNF enhances the synaptic efficacy of dopaminergic neurons in culture
Bourque, M.-J., & Trudeau, L. (2000) · European Journal of Neuroscience · doi:10.1046/j.1460-9568.2000.00219.x · Cited by 163 · see citing works
The ability of the mesocortical dopamine system to operate in distinct temporal modes
Lapish, C. C., Kroener, S., Durstewitz, D., Lavı́n, A., & Seamans, J. K. (2006) · Psychopharmacology · doi:10.1007/s00213-006-0527-8 · Cited by 153 · see citing works
Comparative anatomy of the ventromedial mesencephalic tegmentum in the rat, cat, monkey and human
Halliday, G. M., & Törk, I. (1986) · The Journal of Comparative Neurology · doi:10.1002/cne.902520402 · Cited by 147 · see citing works
A Golgi study of the ventral tegmental area of Tsai and interfascicular nucleus in the rat
Phillipson, O. T. (1979) · The Journal of Comparative Neurology · doi:10.1002/cne.901870107 · Cited by 123 · see citing works
VGLUT2 in dopamine neurons is required for psychostimulant-induced behavioral activation
Birgner, C., Nordenankar, K., Lundblad, M., Méndez, J. A. T., Smith, C., Grevès, M. L., Galter, D., Olson, L., Fredriksson, A., Trudeau, L., et al. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0910986107 · Cited by 119 · see citing works
Tagliaferro, P. A., & Morales, M. (2007) · The Journal of Comparative Neurology · doi:10.1002/cne.21576 · Cited by 107 · 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
Chuhma, N., Choi, W., Mingote, S., & Rayport, S. (2009) · Neuroscience · doi:10.1016/j.neuroscience.2009.08.057 · Cited by 83 · see citing works
Glutamate‐Dopamine Cotransmission and Reward Processing in Addiction
Lapish, C. C., Seamans, J. K., & Chandler, L. J. (2006) · Alcoholism Clinical and Experimental Research · doi:10.1111/j.1530-0277.2006.00176.x · Cited by 82 · see citing works
Ultrastructural localization of tyrosine hydroxylase in rat nucleus accumbens
Bouyer, J. J., JOH, T. H., & Pickel, V. M. (1984) · The Journal of Comparative Neurology · doi:10.1002/cne.902270110 · Cited by 72 · see citing works
Wang, H., & Morales, M. (2008) · The Journal of Comparative Neurology · doi:10.1002/cne.21751 · Cited by 70 · see citing works
Self-citationDale's principle and glutamate corelease from ventral midbrain dopamine neurons
Sulzer, D. L., & Rayport, S. (2000) · Amino Acids · doi:10.1007/s007260070032 · Cited by 64 · see citing works
Chou, Y.-H., Halldin, C., & Farde, L. (2000) · Synapse · doi:10.1002/1098-2396(200011)38:2 · Cited by 57 · see citing works
Gene profiling of laser-microdissected brain regions and sub-regions
Sanna, P. P., King, A. R., van der Stap, L. D., & Repunte‐Canonigo, V. (2005) · Brain Research Protocols · doi:10.1016/j.brainresprot.2005.04.002 · Cited by 16 · see citing works
Mesocortical Dopamine Neurons Operate in Distinct Temporal Domains Using Multimodal Signaling
Lavin, A. (2020) · Carolina Digital Repository (University of North Carolina at Chapel Hill) · doi:10.17615/bjt1-5020 · Cited by 8 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
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
Self-citationThe Nucleus Accumbens: An Interface Between Cognition, Emotion, and Action
Floresco, S. B. (2015) · Annual Review of Psychology · doi:10.1146/annurev-psych-010213-115159 · Cited by 938 · 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
Witten, I. B., Steinberg, E. E., Lee, S. Y., Davidson, T. J., Zalocusky, K. A., Brodsky, M., Yizhar, O., Cho, S. L., Gong, S., Ramakrishnan, C., et al. (2011) · Neuron · doi:10.1016/j.neuron.2011.10.028 · Cited by 680 · see citing works
Activation of VTA GABA Neurons Disrupts Reward Consumption
van Zessen, R., Phillips, J. L., Budygin, E. A., & Stuber, G. D. (2012) · Neuron · doi:10.1016/j.neuron.2012.02.016 · Cited by 609 · 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
A 4 Hz oscillation adaptively synchronizes prefrontal, VTA, and hippocampal activities
Fujisawa, S., & Buzsáki, G. (2011) · Neuron · doi:10.1016/j.neuron.2011.08.018 · Cited by 501 · see citing works
Are you or aren’t you? Challenges associated with physiologically identifying dopamine neurons
Ungless, M. A., & Grace, A. A. (2012) · Trends in Neurosciences · doi:10.1016/j.tins.2012.02.003 · Cited by 431 · see citing works
Fields, H. L., & Margolis, E. B. (2015) · Trends in Neurosciences · doi:10.1016/j.tins.2015.01.002 · Cited by 432 · see citing works
Development of prefrontal cortex
Kolk, S. M., & Rakic, P. (2022) · Neuropsychopharmacology · doi:10.1038/s41386-021-01137-9 · Cited by 378 · see citing works
The ventral pallidum: Subregion-specific functional anatomy and roles in motivated behaviors
Root, D. H., Meléndez, R. I., Záborszky, L., & Napier, T. C. (2015) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2015.03.005 · Cited by 343 · see citing works
Single rodent mesohabenular axons release glutamate and GABA
Root, D. H., Mejias-Aponte, C. A., Zhang, S., Wang, H.-L., Hoffman, A. F., Lupica, C. R., & Morales, M. (2014) · Nature Neuroscience · doi:10.1038/nn.3823 · Cited by 349 · see citing works
Self-citationGABA and glutamate neurons in the VTA regulate sleep and wakefulness
Yu, X., Li, W., Ma, Y., Tossell, K., Harris, J. J., Harding, E. C., Ba, W., Miracca, G., Wang, D., Li, L., et al. (2018) · Nature Neuroscience · doi:10.1038/s41593-018-0288-9 · Cited by 317 · see citing works
Ventral Tegmental Area Glutamate Neurons: Electrophysiological Properties and Projections
Hnasko, T. S., Hjelmstad, G. O., Fields, H. L., & Edwards, R. H. (2012) · Journal of Neuroscience · doi:10.1523/jneurosci.3128-12.2012 · Cited by 287 · see citing works
Neurotransmitter Corelease: Mechanism and Physiological Role
Hnasko, T. S., & Edwards, R. H. (2012) · Annual Review of Physiology · doi:10.1146/annurev-physiol-020911-153315 · Cited by 284 · see citing works
“Robust glutamate-mediated AMPA receptor currents were observed in the ventral striatum but not in the dorsal striatum, even though light evoked dopamine release at both sites (94), consistent with the restricted expression of VGLUT2 by dopamine neurons in the VTA but not in the SNc (53, 54).”
InfluentialDopamine release in the basal ganglia
Rice, M. E., Patel, J. C., & Cragg, S. J. (2011) · Neuroscience · doi:10.1016/j.neuroscience.2011.08.066 · Cited by 281 · see citing works
Striatal Local Circuitry: A New Framework for Lateral Inhibition
Burke, D. A., Rotstein, H. G., & Alvarez, V. A. (2017) · Neuron · doi:10.1016/j.neuron.2017.09.019 · Cited by 263 · see citing works
Dopaminergic and glutamatergic microdomains in a subset of rodent mesoaccumbens axons
Zhang, S., Qi, J., Li, X., Wang, H.-L., Britt, J. P., Hoffman, A. F., Bonci, A., Lupica, C. R., & Morales, M. (2015) · Nature Neuroscience · doi:10.1038/nn.3945 · Cited by 252 · see citing works
Self-citationRole of Dopamine Neurons in Reward and Aversion: A Synaptic Plasticity Perspective
Pignatelli, M., & Bonci, A. (2015) · Neuron · doi:10.1016/j.neuron.2015.04.015 · Cited by 244 · see citing works
Classification of midbrain dopamine neurons using single-cell gene expression profiling approaches
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
Matsui, A., Jarvie, B. C., Robinson, B. G., Hentges, S. T., & Williams, J. T. (2014) · Neuron · doi:10.1016/j.neuron.2014.04.030 · Cited by 237 · see citing works
Recent Advances in the Detection of Neurotransmitters
Si, B., & Song, E. (2018) · Chemosensors · doi:10.3390/chemosensors6010001 · Cited by 222 · 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
Self-citationBossert, J. M., Stern, A. L., Theberge, F. R. M., Marchant, N. J., Wang, H.-L., Morales, M., & Shaham, Y. (2012) · The Journal of Neuroscience · doi:10.1523/jneurosci.0005-12.2012 · Cited by 223 · see citing works
Self-citationRoot, D. H., Mejías-Aponte, C. A., Qi, J., & Morales, M. (2014) · Journal of Neuroscience · doi:10.1523/jneurosci.2029-14.2014 · Cited by 213 · see citing works
Self-citationVentral tegmental area glutamate neurons co-release GABA and promote positive reinforcement
Yoo, J. H., Zell, V., Gutierrez-Reed, N. A., Wu, J., Ressler, R. L., Shenasa, M. A., Johnson, A. B., Fife, K. H., Faget, L. C., & Hnasko, T. S. (2016) · Nature Communications · doi:10.1038/ncomms13697 · Cited by 210 · see citing works
GABAergic and glutamatergic efferents of the mouse ventral tegmental area
Taylor, S. R., Badurek, S., Dileone, R., Nashmi, R., Minichiello, L., & Picciotto, M. R. (2014) · The Journal of Comparative Neurology · doi:10.1002/cne.23603 · Cited by 209 · see citing works
VTA glutamatergic inputs to nucleus accumbens drive aversion by acting on GABAergic interneurons
Qi, J., Zhang, S., Wang, H., Barker, D. J., Miranda-Barrientos, J. A., & Morales, M. (2016) · Nature Neuroscience · doi:10.1038/nn.4281 · Cited by 203 · see citing works
Self-citationIdentification of Rat Ventral Tegmental Area GABAergic Neurons
Margolis, E. B., Toy, B. C., Himmels, P., Morales, M., & Fields, H. L. (2012) · PLoS ONE · doi:10.1371/journal.pone.0042365 · Cited by 202 · see citing works
Self-citationA glutamatergic reward input from the dorsal raphe to ventral tegmental area dopamine neurons
Qi, J., Zhang, S. S., Wang, H., Wang, H., Buendia, J. D. J. A., Hoffman, A. F., Lupica, C. R., Seal, R. P., & Morales, M. (2014) · Nature Communications · doi:10.1038/ncomms6390 · Cited by 195 · see citing works
Self-citationLecca, S., Melis, M., Luchicchi, A., Muntoni, A. L., & Pistis, M. (2011) · Neuropsychopharmacology · doi:10.1038/npp.2011.302 · Cited by 185 · see citing works
Afferent Inputs to Neurotransmitter-Defined Cell Types in the Ventral Tegmental Area
Faget, L. C., Osakada, F., Duan, J., Ressler, R. L., Johnson, A. B., Proudfoot, J., Yoo, J. H., Callaway, E. M., & Hnasko, T. S. (2016) · Cell Reports · doi:10.1016/j.celrep.2016.05.057 · Cited by 180 · see citing works
Dopamine neurons projecting to medial shell of the nucleus accumbens drive heroin reinforcement
Corre, J., van Zessen, R., Loureiro, M., Patriarchi, T., Tian, L., Pascoli, V., & Lüscher, C. (2018) · eLife · doi:10.7554/elife.39945 · Cited by 168 · see citing works
An update on the connections of the ventral mesencephalic dopaminergic complex
Yetnikoff, L., Lavezzi, H. N., Reichard, R. A., & Zahm, D. S. (2014) · Neuroscience · doi:10.1016/j.neuroscience.2014.04.010 · Cited by 172 · see citing works
Volman, S. F., Lammel, S., Margolis, E. B., Kim, Y., Richard, J. M., Roitman, M. F., & Lobo, M. K. (2013) · The Journal of Neuroscience · doi:10.1523/jneurosci.3250-13.2013 · Cited by 168 · see citing works
The control of sleep and wakefulness by mesolimbic dopamine systems
Oishi, Y., & Lazarus, M. (2017) · Neuroscience Research · doi:10.1016/j.neures.2017.04.008 · Cited by 159 · see citing works
Peris, J., MacFadyen, K. A., Smith, J. A., de Kloet, A. D., Wang, L. A., & Krause, E. G. (2016) · The Journal of Comparative Neurology · doi:10.1002/cne.24116 · Cited by 158 · see citing works
Flagel, S. B., Cameron, C., Pickup, K. N., Watson, S. J., Akil, H., & Robinson, T. E. (2011) · Neuroscience · doi:10.1016/j.neuroscience.2011.09.004 · Cited by 153 · see citing works
Intrinsic plasticity: an emerging player in addiction
Kourrich, S., Calu, D. J., & Bonci, A. (2015) · Nature reviews. Neuroscience · doi:10.1038/nrn3877 · Cited by 151 · see citing works
Root, D. H., Zhang, S., Barker, D. J., Miranda-Barrientos, J., Liu, B., Wang, H.-L., & Morales, M. (2018) · Cell Reports · doi:10.1016/j.celrep.2018.05.063 · Cited by 153 · see citing works
Self-citationRapid, transient synaptic plasticity in addiction
Gipson, C. D., Kupchik, Y. M., & Kalivas, P. W. (2013) · Neuropharmacology · doi:10.1016/j.neuropharm.2013.04.032 · Cited by 145 · see citing works
Aransay, A., Rodríguez-López, C., García‐Amado, M., Clascá, F., & Prensa, L. (2015) · Frontiers in Neuroanatomy · doi:10.3389/fnana.2015.00059 · Cited by 143 · see citing works
The multilingual nature of dopamine neurons
Trudeau, L., Hnasko, T. S., Wallén‐Mackenzie, Å., Morales, M., Rayport, S., & Sulzer, D. L. (2014) · Progress in brain research · doi:10.1016/b978-0-444-63425-2.00006-4 · Cited by 138 · see citing works
Self-citationAfferents to anterior cingulate areas 24a and 24b and midcingulate areas 24a′ and 24b′ in the mouse
Fillinger, C., Yalçın, İ., Barrot, M., & Veinante, P. (2016) · Brain Structure and Function · doi:10.1007/s00429-016-1290-1 · Cited by 139 · see citing works
Glutamatergic and dopaminergic neurons in the mouse ventral tegmental area
Yamaguchi, T., Qi, J., Wang, H., Zhang, S. S., & Morales, M. (2015) · European Journal of Neuroscience · doi:10.1111/ejn.12818 · Cited by 139 · see citing works
Self-citationTejeda, H. A., Wu, J., Kornspun, A. R., Pignatelli, M., Kashtelyan, V., Krashes, M. J., Lowell, B. B., Carlezon, W. A., & Bonci, A. (2017) · Neuron · doi:10.1016/j.neuron.2016.12.005 · Cited by 134 · see citing works
Tejeda, H. A., Counotte, D. S., Oh, E. J., Ramamoorthy, S., Schultz‐Kuszak, K., Bäckman, C. M., Chefer, V., O’Donnell, P., & Shippenberg, T. S. (2013) · Neuropsychopharmacology · doi:10.1038/npp.2013.76 · Cited by 132 · see citing works
Li, X., Qi, J., Yamaguchi, T., Wang, H., & Morales, M. (2012) · Brain Structure and Function · doi:10.1007/s00429-012-0452-z · Cited by 129 · see citing works
Self-citationMuscarinic regulation of dopamine and glutamate transmission in the nucleus accumbens
Shin, J. H., Adrover, M. F., Wess, J., & Alvarez, V. A. (2015) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1508846112 · Cited by 129 · see citing works
Development, wiring and function of dopamine neuron subtypes
Garritsen, O., van Battum, E. Y., Grossouw, L. M., & Pasterkamp, R. J. (2023) · Nature reviews. Neuroscience · doi:10.1038/s41583-022-00669-3 · Cited by 128 · see citing works
Lateral Preoptic Control of the Lateral Habenula through Convergent Glutamate and GABA Transmission
Barker, D. J., Miranda-Barrientos, J. A., Zhang, S., Root, D. H., Wang, H.-L., Liu, B., Calipari, E. S., & Morales, M. (2017) · Cell Reports · doi:10.1016/j.celrep.2017.10.066 · Cited by 125 · see citing works
Self-citationRoot, D. H., Barker, D. J., Estrin, D. J., Miranda-Barrientos, J. A., Liu, B., Zhang, S., Wang, H.-L., Vautier, F., Ramakrishnan, C., Kim, Y. S., et al. (2020) · Cell Reports · doi:10.1016/j.celrep.2020.108094 · Cited by 128 · see citing works
Self-citationSego, C., Gonçalves, L., Lima, L. B., Furigo, I. C., Donato, J., & Metzger, M. (2013) · The Journal of Comparative Neurology · doi:10.1002/cne.23533 · Cited by 126 · see citing works
VTA Glutamate Neuron Activity Drives Positive Reinforcement Absent Dopamine Co-release
Zell, V., Steinkellner, T., Hollon, N. G., Warlow, S. M., Souter, E. A., Faget, L. C., Hunker, A. C., Jin, X., Zweifel, L. S., & Hnasko, T. S. (2020) · Neuron · doi:10.1016/j.neuron.2020.06.011 · Cited by 127 · see citing works
VTA Glutamatergic Neurons Mediate Innate Defensive Behaviors
Barbano, M. F., Wang, H.-L., Zhang, S., Miranda-Barrientos, J. A., Estrin, D. J., Figueroa‐González, A., Liu, B., Barker, D. J., & Morales, M. (2020) · Neuron · doi:10.1016/j.neuron.2020.04.024 · Cited by 124 · see citing works
Self-citationLiu, S., Plachez, C., Shao, Z., Puché, A. C., & Shipley, M. T. (2013) · Journal of Neuroscience · doi:10.1523/jneurosci.3607-12.2013 · Cited by 124 · see citing works
The Evolving Understanding of Dopamine Neurons in the Substantia Nigra and Ventral Tegmental Area
Gantz, S. C., Ford, C., Morikawa, H., & Williams, J. T. (2017) · Annual Review of Physiology · doi:10.1146/annurev-physiol-021317-121615 · Cited by 122 · see citing works
Rewarding Effects of Optical Stimulation of Ventral Tegmental Area Glutamatergic Neurons
Wang, H., Qi, J., Zhang, S. S., Wang, H., & Morales, M. (2015) · Journal of Neuroscience · doi:10.1523/jneurosci.3428-15.2015 · Cited by 119 · see citing works
Self-citationBreton, J., Charbit, A. R., Snyder, B. J., Fong, P. T. K., Dias, E. V., Himmels, P., Lock, H., & Margolis, E. B. (2018) · The Journal of Comparative Neurology · doi:10.1002/cne.24572 · Cited by 118 · see citing works
Revel, F. G., Meyer, C. A., Bradaïa, A., Jeanneau, K., Calcagno, E., André, C. B., Hänggi, M., Miss, M.-T., Galley, G., Norcross, R. D., et al. (2012) · Neuropsychopharmacology · doi:10.1038/npp.2012.109 · Cited by 114 · see citing works
Pistillo, F., Clementi, F., Zoli, M., & Gotti, C. (2014) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2014.10.002 · Cited by 113 · see citing works
Witek, K., Wydra, K., & Filip, M. (2022) · Nutrients · doi:10.3390/nu14142940 · Cited by 128 · see citing works
An atlas of transcriptionally defined cell populations in the rat ventral tegmental area
Phillips, R. A., Tuscher, J. J., Black, S. L., Andraka, E., Fitzgerald, N. D., Ianov, L., & Day, J. J. (2022) · Cell Reports · doi:10.1016/j.celrep.2022.110616 · Cited by 114 · see citing works
Considerations When Using Cre-Driver Rodent Lines for Studying Ventral Tegmental Area Circuitry
Stuber, G. D., Stamatakis, A. M., & Kantak, P. A. (2015) · Neuron · doi:10.1016/j.neuron.2014.12.034 · Cited by 104 · 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
Glutamate neurons are intermixed with midbrain dopamine neurons in nonhuman primates and humans
Root, D. H., Wang, H., Liu, B., Barker, D. J., Mód, L., Szocsics, P., Silva, A. C., Maglóczky, Z., & Morales, M. (2016) · Scientific Reports · doi:10.1038/srep30615 · Cited by 98 · see citing works
Self-citationBossert, J. M., Adhikary, S., Laurent, R. S., Marchant, N. J., Wang, H.-L., Morales, M., & Shaham, Y. (2015) · Psychopharmacology · doi:10.1007/s00213-015-4060-5 · Cited by 99 · see citing works
Self-citationMultiplexed neurochemical signaling by neurons of the ventral tegmental area
Barker, D. J., Root, D. H., Zhang, S., & Morales, M. (2016) · Journal of Chemical Neuroanatomy · doi:10.1016/j.jchemneu.2015.12.016 · Cited by 99 · see citing works
Self-citationMaternal Immune Activation Disrupts Dopamine System in the Offspring
Luchicchi, A., Lecca, S., Melis, M., Felice, M. D., Cadeddu, F., Frau, R., Muntoni, A. L., Fadda, P., Devoto, P., & Pistis, M. (2016) · The International Journal of Neuropsychopharmacology · doi:10.1093/ijnp/pyw007 · Cited by 96 · see citing works
Zhang, L., & Hernández, V. S. (2013) · Neuroscience · doi:10.1016/j.neuroscience.2012.10.010 · Cited by 96 · see citing works
Functional Connectome Analysis of Dopamine Neuron Glutamatergic Connections in Forebrain Regions
Mingote, S., Chuhma, N., Kusnoor, S. V., Field, B. C., Deutch, A. Y., & Rayport, S. (2015) · Journal of Neuroscience · doi:10.1523/jneurosci.1674-15.2015 · Cited by 93 · see citing works
Sobolewski, M., Conrad, K., Allen, J. L., Weston, H., Martin, K., Lawrence, B. P., & Cory-Slechta, D. A. (2014) · NeuroToxicology · doi:10.1016/j.neuro.2014.09.008 · Cited by 91 · see citing works
Aversion or Salience Signaling by Ventral Tegmental Area Glutamate Neurons
Root, D. H., Estrin, D. J., & Morales, M. (2018) · iScience · doi:10.1016/j.isci.2018.03.008 · Cited by 89 · see citing works
Self-citationAnatomy and Function of Ventral Tegmental Area Glutamate Neurons
Cai, J., & Tong, Q. (2022) · Frontiers in Neural Circuits · doi:10.3389/fncir.2022.867053 · Cited by 89 · see citing works
Massi, L., Lagler, M., Hartwich, K., Borhegyi, Z., Somogyi, P., & Klausberger, T. (2012) · The Journal of Neuroscience · doi:10.1523/jneurosci.3475-12.2012 · Cited by 88 · see citing works
Alsiö, J., Nordenankar, K., Arvidsson, E., Birgner, C., Mahmoudi, S., Halbout, B., Smith, C., Fortin, G. M., Olson, L., Descarries, L., et al. (2011) · Journal of Neuroscience · doi:10.1523/jneurosci.2397-11.2011 · Cited by 88 · see citing works
Sex differences in the glutamate system: Implications for addiction
Giacometti, L. L., & Barker, J. M. (2020) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2020.03.010 · Cited by 87 · see citing works
Glutamate neurons in the substantia nigra compacta and retrorubral field
Yamaguchi, T., Wang, H., & Morales, M. (2013) · European Journal of Neuroscience · doi:10.1111/ejn.12359 · Cited by 87 · see citing works
Self-citationEnhanced serotonin and mesolimbic dopamine transmissions in a rat model of neuropathic pain
Sagheddu, C., Aroni, S., Felice, M. D., Lecca, S., Luchicchi, A., Melis, M., Muntoni, A. L., Romano, R., Palazzo, E., Guida, F., et al. (2015) · Neuropharmacology · doi:10.1016/j.neuropharm.2015.06.003 · Cited by 86 · 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
“Approximately two thirds of the neurons in the VTA are dopaminergic, and the majority of the remaining neurons are GABAergic (Swanson, 1982; Nair-Roberts et al., 2008; Sesack and Grace, 2010).”
BackgroundInfluentialRole of corticostriatal circuits in context-induced reinstatement of drug seeking
Marchant, N. J., Kaganovsky, K., Shaham, Y., & Bossert, J. M. (2014) · Brain Research · doi:10.1016/j.brainres.2014.09.004 · Cited by 81 · see citing works
Boswell, R. G., Potenza, M. N., & Grilo, C. M. (2020) · Clinical Therapeutics · doi:10.1016/j.clinthera.2020.10.014 · Cited by 82 · see citing works
Hub and switches: endocannabinoid signalling in midbrain dopamine neurons
Melis, M., & Pistis, M. (2012) · Philosophical Transactions of the Royal Society B Biological Sciences · doi:10.1098/rstb.2011.0383 · Cited by 79 · see citing works
Doyon, W. M., Thomas, A. M., Ostroumov, A., Dong, Y., & Dani, J. A. (2013) · Biochemical Pharmacology · doi:10.1016/j.bcp.2013.07.007 · Cited by 77 · see citing works
DePuy, S. D., Stornetta, R. L., Bochorishvili, G., Deisseroth, K. A., Witten, I. B., Coates, M. B., & Guyenet, P. G. (2013) · Journal of Neuroscience · doi:10.1523/jneurosci.4269-12.2013 · Cited by 78 · see citing works
Glutamate Corelease Promotes Growth and Survival of Midbrain Dopamine Neurons
Fortin, G. M., Bourque, M.-J., Méndez, J. A. T., Leo, D., Nordenankar, K., Birgner, C., Arvidsson, E., Rymar, V. V., Bérubé‐Carrière, N., Claveau, A.-M., et al. (2012) · Journal of Neuroscience · doi:10.1523/jneurosci.1939-12.2012 · Cited by 77 · see citing works
Role of Cannabidiol in the Therapeutic Intervention for Substance Use Disorders
Navarrete, F., García‐Gutiérrez, M. S., Gasparyan, A., Austrich-Olivares, A., & Manzanares, J. (2021) · Frontiers in Pharmacology · doi:10.3389/fphar.2021.626010 · Cited by 78 · see citing works
Adrover, M. F., Shin, J. H., & Alvarez, V. A. (2014) · Journal of Neuroscience · doi:10.1523/jneurosci.4958-13.2014 · Cited by 75 · see citing works
Dopamine-glutamate neuron projections to the nucleus accumbens medial shell and behavioral switching
Mingote, S., Amsellem, A., Kempf, A., Rayport, S., & Chuhma, N. (2019) · Neurochemistry International · doi:10.1016/j.neuint.2019.104482 · Cited by 71 · see citing works
van Zessen, R., Plasse, G., & Adan, R. A. H. (2012) · Proceedings of The Nutrition Society · doi:10.1017/s0029665112000614 · Cited by 70 · see citing works
Tang, Y., Chen, Z., Tao, H., Li, C., Zhang, X., Tang, A., & Liu, Y. (2014) · Neuropharmacology · doi:10.1016/j.neuropharm.2013.10.004 · Cited by 68 · see citing works
Ghanbarian, E., & Motamedi, F. (2013) · PLoS ONE · doi:10.1371/journal.pone.0058844 · Cited by 67 · see citing works
Xin, J., Shan, W., Li, J., Yu, H., & Zuo, Z. (2022) · Advanced Science · doi:10.1002/advs.202202228 · Cited by 66 · see citing works
Weisenhorn, D. M. V., Giesert, F., & Wurst, W. (2016) · Journal of Neurochemistry · doi:10.1111/jnc.13670 · Cited by 67 · see citing works
Leptin/LepRb in the Ventral Tegmental Area Mediates Anxiety-Related Behaviors
Liu, J., Guo, M., & Lu, X. (2015) · The International Journal of Neuropsychopharmacology · doi:10.1093/ijnp/pyv115 · Cited by 65 · see citing works
The Formation and Function of the VTA Dopamine System
Hou, G., Hao, M., Duan, J., & Han, M.-H. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25073875 · Cited by 65 · see citing works
Estrous Cycle Mediates Midbrain Neuron Excitability Altering Social Behavior upon Stress
Shanley, M. R., Miura, Y., Guevara, C. A., Onoichenco, A., Kore, R., Ustundag, E., Darwish, R., Renzoni, L., Sanchez, A. M. S., Blicker, E., et al. (2022) · Journal of Neuroscience · doi:10.1523/jneurosci.1504-22.2022 · Cited by 63 · see citing works
Function and developmental origin of a mesocortical inhibitory circuit
Kabanova, A., Pabst, M., Lorkowski, M., Braganza, O., Boehlen, A., Nikbakht, N., Pothmann, L., Vaswani, A. R., Musgrove, R., Di Monte, D. A., et al. (2015) · Nature Neuroscience · doi:10.1038/nn.4020 · Cited by 61 · see citing works
Ventral Tegmental Area Afferents and Drug-Dependent Behaviors
Oliva, I., & Wanat, M. J. (2016) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2016.00030 · Cited by 62 · see citing works
Warlow, S. M., Singhal, S. M., Hollon, N. G., Faget, L. C., Dowlat, D. S., Zell, V., Hunker, A. C., Zweifel, L. S., & Hnasko, T. S. (2023) · Neuron · doi:10.1016/j.neuron.2023.11.002 · Cited by 59 · see citing works
- Authors
- Yamaguchi, T., Wang, H.-L., Li, X., Ng, T. H., & Morales, M.
- Affiliations
- National Institute on Drug Abuse (US)
- Corresponding author
- Morales, M.
- Venue
- Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2011-06-08
- Volume
- 31
- Issue
- 23
- Pages
- 8476-8490
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC6623324
- OpenAlex
- W2010408327
- Cited by
- 332
- References
- 38
- Citations by year
- 2026: 8 · 2025: 20 · 2024: 32 · 2023: 23 · 2022: 19 · 2021: 16 · 2020: 24 · 2019: 18 · 2018: 19 · 2017: 20 · 2016: 22 · 2015: 33 · 2014: 26 · 2013: 22 · 2012: 18
- FWCI
- 10.33
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Neuroscience (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Institute on Drug Abuse
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Health Sciences › Medicine › Neurology › Neurological disorders and treatments
- Keywords
- ventral tegmental area, vesicular glutamate transporter 2, tyrosine hydroxylase, dopaminergic neurons, prefrontal cortex, nucleus accumbens, GABAergic neurons, neuronal subpopulations
- MeSH terms
- Animals, Dopamine, Immunohistochemistry, Neurons, Nucleus Accumbens, Raphe Nuclei, RNA, Messenger, Tyrosine 3-Monooxygenase, Rats, Sprague-Dawley, In Situ Hybridization, Ventral Tegmental Area, Glutamic Acid, Reverse Transcriptase Polymerase Chain Reaction, Vesicular Glutamate Transport Protein 2, Rats, Neuronal Tract-Tracers
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
