Lateral Habenula Stimulation Inhibits Rat Midbrain Dopamine Neurons through a GABAA Receptor-Mediated Mechanism
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Transient changes in the activity of midbrain dopamine neurons encode an error signal that contributes to associative learning. Although considerable attention has been devoted to the mechanisms contributing to phasic increases in dopamine activity, less is known about the origin of the transient cessation in firing accompanying the unexpected loss of a predicted reward. Recent studies suggesting that the lateral habenula (LHb) may contribute to this type of signaling in humans prompted us to evaluate the effects of LHb stimulation on the activity of dopamine and non-dopamine neurons of the anesthetized rat. Single-pulse stimulation of the LHb (0.5 mA, 100 micros) transiently suppressed the activity of 97% of the dopamine neurons recorded in the substantia nigra and ventral tegmental area. The duration of the cessation averaged approximately 85 ms and did not differ between the two regions. Identical stimuli transiently excited 52% of the non-dopamine neurons in the ventral midbrain. Electrolytic lesions of the fasciculus retroflexus blocked the effects of LHb stimulation on dopamine neurons. Local application of bicuculline but not the SK-channel blocker apamin attenuated the effects of LHb stimulation on dopamine cells, indicating that the response is mediated by GABA(A) receptors. These data suggest that LHb-induced suppression of dopamine cell activity is mediated indirectly by orthodromic activation of putative GABAergic neurons in the ventral midbrain. The habenulomesencephalic pathway, which is capable of transiently suppressing the activity of dopamine neurons at a population level, may represent an important component of the circuitry involved in encoding reward expectancy.
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RMTg neurons project to the VTA and largely mediate the inhibitory action of lateral habenula projections onto VTA dopaminergic neurons.
“RMTg neurons, in turn, project to the VTA and are largely responsible for the predominantly inhibitory action of LHb projections onto VTA dopaminergic neurons [256].”
From Plasticity of synapses and reward circuit function in the genesis and treatment of depression (2023) · cites this paper as [256]
Electrical stimulation of the LHb inhibits most DA neurons indirectly via the RMTg.
“Furthermore, electrical stimulation of the LHb inhibits the vast majority of DA neurons [69, 71, 72]. Such inhibition is not direct, but rather occurs through the stimulation of neurons in the rostromedial tegmental nucleus (RMTg) [73].”
From Mechanistic insights into nicotine withdrawal (2011) · cites this paper as [72]
LHb has an inhibitory influence on dopaminergic neurons via GABAergic interneurons in RMTg, reflected by lesioning of habenula increasing cortical and striatal dopamine.
“It was shown that the LHb has an inhibitory influence on dopaminergic neurons (Matsumoto and Hikosaka, 2007) via GABAergic interneurons in the rostromedial tegmental nucleus (Ji and Shepard, 2007; Jhou et al., 2009), which is reflected by the fact that lesioning of the habenula leads to an increase of cortical and striatal dopamine levels (Nishikawa et al., 1986).”
From Circuit Mechanisms of Reward, Anhedonia, and Depression (2019) · cites this paper as Ji and Shepard, 2007
Habenula stimulation elicits inhibitory electrophysiological dopamine responses through an intermediate reticular nucleus, rather than the excitatory responses required for a postulated aversive dopamine influence on place preferences.
“In support of the latter result, habenula stimulation elicits inhibitory electrophysiological dopamine responses139–141 through an intermediate reticular nucleus138, rather than the excitatory responses required for a postulated aversive dopamine influence on place preferences137.”
From Dopamine reward prediction-error signalling: A two-component response (2016) · cites this paper as [140]
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Cites
A neural substrate of prediction and reward
Schultz, W., Dayan, P., & Montague, P. R. (1997) · Science · doi:10.1126/science.275.5306.1593 · Cited by 9,388 · see citing works
Discrete coding of reward probability and uncertainty by dopamine neurons
Fiorillo, C. D., Tobler, P. N., & Schultz, W. (2003) · Science · doi:10.1126/science.1077349 · Cited by 2,085 · see citing works
The control of firing pattern in nigral dopamine neurons: burst firing
Grace, A., & Bunney, B. (1984) · Journal of Neuroscience · doi:10.1523/jneurosci.04-11-02877.1984 · Cited by 1,346 · see citing works
Lateral habenula as a source of negative reward signals in dopamine neurons
Matsumoto, M., & Hikosaka, O. (2007) · Nature · doi:10.1038/nature05860 · Cited by 1,292 · see citing works
Schultz, W., Apicella, P., & Ljungberg, T. (1993) · The Journal of Neuroscience · doi:10.1523/jneurosci.13-03-00900.1993 · Cited by 1,291 · see citing works
DOPAMINERGIC NEURONS: EFFECT OF ANTIPSYCHOTIC DRUGS AND AMPHETAMINE ON SINGLE CELL ACTIVITY
Bunney, B. S., Walters, J. R., Roth, R. H., & Aghajanian, G. K. (1973) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(25)29539-8 · Cited by 1,283 · see citing works
Responses of monkey dopamine neurons during learning of behavioral reactions
Ljungberg, T., Apicella, P., & Schultz, W. (1992) · Journal of Neurophysiology · doi:10.1152/jn.1992.67.1.145 · Cited by 987 · see citing works
Grace, A. A., & Bunney, B. S. (1983) · Neuroscience · doi:10.1016/0306-4522(83)90135-5 · Cited by 937 · see citing works
Efferent connections of the habenular nuclei in the rat
Herkenham, M. A., & Nauta, W. J. H. (1979) · The Journal of Comparative Neurology · doi:10.1002/cne.901870103 · Cited by 855 · see citing works
Phillipson, O. T. (1979) · The Journal of Comparative Neurology · doi:10.1002/cne.901870108 · Cited by 553 · see citing works
Midbrain dopamine neurons encode decisions for future action
Morris, G., Nevet, A., Arkadir, D., Vaadia, E., & Bergman, H. (2006) · Nature Neuroscience · doi:10.1038/nn1743 · Cited by 503 · see citing works
Antidromic identification of dopaminergic and other output neurons of the rat substantia nigra
Guyenet, P. G., & Aghajanian, G. K. (1978) · Brain Research · doi:10.1016/0006-8993(78)90654-6 · Cited by 500 · see citing works
Ullsperger, M., & von Cramon, D. Y. (2003) · Journal of Neuroscience · doi:10.1523/jneurosci.23-10-04308.2003 · Cited by 484 · see citing works
Pan, W.-X., Schmidt, R., Wickens, J. R., & Hyland, B. I. (2005) · The Journal of Neuroscience · doi:10.1523/jneurosci.1478-05.2005 · Cited by 429 · see citing works
Christoph, G., Leonzio, R., & Wilcox, K. (1986) · The Journal of Neuroscience · doi:10.1523/jneurosci.06-03-00613.1986 · Cited by 418 · see citing works
Physiological Evidence for Habenula as Major Link Between Forebrain and Midbrain Raphe
Wang, R. Y., & Aghajanian, G. K. (1977) · Science · doi:10.1126/science.194312 · Cited by 411 · see citing works
Grace, A. A., & Bunney, B. S. (1979) · European Journal of Pharmacology · doi:10.1016/0014-2999(79)90283-8 · Cited by 392 · see citing works
Electrophysiological Characterization of GABAergic Neurons in the Ventral Tegmental Area
Steffensen, S. C., Svingos, A. L., Pickel, V. M., & Henriksen, S. J. (1998) · Journal of Neuroscience · doi:10.1523/jneurosci.18-19-08003.1998 · Cited by 388 · see citing works
Bunney, B. S., & Aghajanian, G. K. (1976) · Brain Research · doi:10.1016/0006-8993(76)90751-4 · Cited by 378 · see citing works
Tepper, J. M., Martin, L., & Anderson, D. (1995) · Journal of Neuroscience · doi:10.1523/jneurosci.15-04-03092.1995 · Cited by 362 · see citing works
Hugues, M., Romey, G., Duval, D., Vincent, J., & Lazdunski, M. (1982) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.79.4.1308 · Cited by 348 · see citing works
Coding of Predicted Reward Omission by Dopamine Neurons in a Conditioned Inhibition Paradigm
Tobler, P. N., Dickinson, A., & Schultz, W. (2003) · The Journal of Neuroscience · doi:10.1523/jneurosci.23-32-10402.2003 · Cited by 300 · see citing works
Correlated Coding of Motivation and Outcome of Decision by Dopamine Neurons
Satoh, T., Nakai, S., Sato, T., & Kimura, M. (2003) · The Journal of Neuroscience · doi:10.1523/jneurosci.23-30-09913.2003 · Cited by 298 · see citing works
Gariano, R. F., & Groves, P. M. (1988) · Brain Research · doi:10.1016/0006-8993(88)90606-3 · Cited by 286 · see citing works
Lecourtier, L., & Kelly, P. H. (2007) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2007.01.004 · Cited by 283 · see citing works
Burst activity of ventral tegmental dopamine neurons is elicited by sensory stimuli in the awake cat
Horvitz, J. C., Stewart, T., & Jacobs, B. L. (1997) · Brain Research · doi:10.1016/s0006-8993(97)00265-5 · Cited by 283 · see citing works
Opposing effects of striatonigral feedback pathways on midbrain dopamine cell activity
Grace, A. A., & Bunney, B. S. (1985) · Brain Research · doi:10.1016/0006-8993(85)91581-1 · Cited by 280 · see citing works
Dopamine Neurons Can Represent Context-Dependent Prediction Error
Nakahara, H., Itoh, H., Kawagoe, R., Takikawa, Y., & Hikosaka, O. (2004) · Neuron · doi:10.1016/s0896-6273(03)00869-9 · Cited by 276 · see citing works
Dopaminergic neurons in the rat ventral tegmental area. I. Identification and characterization
Wang, R. Y. (1981) · Brain Research Reviews · doi:10.1016/0165-0173(81)90002-3 · Cited by 244 · see citing works
Firing properties of substantia nigra dopaminergic neurons in freely moving rats
Freeman, A. S., Meltzer, L. T., & Bunney, B. S. (1985) · Life Sciences · doi:10.1016/0024-3205(85)90448-5 · Cited by 236 · see citing works
Richards, C. D., Shiroyama, T., & Kitai, S. T. (1997) · Neuroscience · doi:10.1016/s0306-4522(97)00093-6 · Cited by 233 · see citing works
Role of the subthalamic nucleus in the regulation of nigral dopamine neuron activity
Smith, I. D., & Grace, A. A. (1992) · Synapse · doi:10.1002/syn.890120406 · Cited by 232 · see citing works
Pan, W. X., & Hyland, B. I. (2005) · Journal of Neuroscience · doi:10.1523/jneurosci.0277-05.2005 · Cited by 209 · see citing works
Substance P containing and cholinergic projections from the habenula
Claudio Cuello, A., Emson, P. C., Paxinos, G., & Jessell, T. (1978) · Brain Research · doi:10.1016/0006-8993(78)90484-5 · Cited by 197 · see citing works
SK channels in excitability, pacemaking and synaptic integration
Bond, C. T., Maylie, J., & Adelman, J. P. (2005) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2005.05.001 · Cited by 180 · see citing works
Bicuculline block of small-conductance calcium-activated potassium channels
Khawaled, R., Bruening‐Wright, A., Adelman, J. P., & Maylie, J. (1999) · Pflügers Archiv - European Journal of Physiology · doi:10.1007/s004240050915 · Cited by 179 · see citing works
Mesencephalic dopaminergic unit activity in the behaviorally conditioned rat
Miller, J. D., Sanghera, M. K., & German, D. C. (1981) · Life Sciences · doi:10.1016/0024-3205(81)90231-9 · Cited by 170 · see citing works
Nishikawa, T., Fage, D., & Scatton, B. (1986) · Brain Research · doi:10.1016/0006-8993(86)90347-1 · Cited by 166 · see citing works
Kalén, P., Karlson, M., & Wiklund, L. (1985) · Brain Research · doi:10.1016/0006-8993(85)91244-2 · Cited by 148 · see citing works
Paladini, C. A., Celada, P., & Tepper, J. M. (1999) · Neuroscience · doi:10.1016/s0306-4522(98)00355-8 · Cited by 141 · see citing works
Shepard, D. S., Holcomb, H. H., & Gold, J. M. (2005) · Schizophrenia Bulletin · doi:10.1093/schbul/sbj083 · Cited by 140 · see citing works
Davey, N. J., ELLAWAY, P. H., & Stein, R. B. (1986) · Journal of Neuroscience Methods · doi:10.1016/0165-0270(86)90068-3 · Cited by 133 · see citing works
Lisoprawski, A., Herve, D., Blanc, G., Glowinski, J., & Tassin, J. P. (1980) · Brain Research · doi:10.1016/0006-8993(80)90135-3 · Cited by 130 · see citing works
Mailly, P., Charpier, S., Menetrey, A., & Deniau, J. (2003) · Journal of Neuroscience · doi:10.1523/jneurosci.23-12-05247.2003 · Cited by 129 · see citing works
Geisler, S., Andres, K. H., & Veh, R. W. (2003) · The Journal of Comparative Neurology · doi:10.1002/cne.10566 · Cited by 128 · see citing works
Recent advances in the pharmacology of quaternary salts of bicuculline
Seutin, V., & Johnson, S. W. (1999) · Trends in Pharmacological Sciences · doi:10.1016/s0165-6147(99)01334-6 · Cited by 126 · see citing works
Identification and characterization
Bernstein, J., & Reutzel‐Edens, S. M. (2019) · urn:isbn:978-1-118-41628-0 · Cited by 112 · see citing works
Gervais, J., & Rouillard, C. (2000) · Synapse · doi:10.1002/(sici)1098-2396(20000315)35:4 · Cited by 109 · see citing works
Kiyatkin, E. A., & Rebec, G. V. (1998) · Neuroscience · doi:10.1016/s0306-4522(98)00054-2 · Cited by 107 · see citing works
SK channels control the firing pattern of midbrain dopaminergic neurons <i>in vivo</i>
Waroux, O., Massotte, L., Alleva, L., Graulich, A., Thomas, E., Liégeois, J., Scuvée‐Moreau, J., & Seutin, V. (2005) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2005.04484.x · Cited by 103 · see citing works
Lateral Habenular Influence on Dorsal Raphe Neurons
Ferraro, G., Montalbano, M. E., Sardo, P., & Grutta, V. L. (1996) · Brain Research Bulletin · doi:10.1016/0361-9230(96)00170-0 · Cited by 100 · see citing works
O’Brien, D. P., & White, F. J. (1987) · European Journal of Pharmacology · doi:10.1016/0014-2999(87)90072-0 · Cited by 76 · see citing works
Dougherty, K. D., & Milner, T. A. (1999) · The Journal of Comparative Neurology · doi:10.1002/(sici)1096-9861(19990428)407:1 · Cited by 76 · see citing works
Transmitters contained in the efferents of the habenula
Vincent, S. R., Staines, W. A., McGeer, E. G., & Fibiger, H. C. (1980) · Brain Research · doi:10.1016/0006-8993(80)90084-0 · Cited by 74 · see citing works
Steward, O., Tomasulo, R. A., & Levy, W. B. (1990) · Brain Research · doi:10.1016/0006-8993(90)90930-a · Cited by 72 · see citing works
Intravenous GABA agonist administration stimulates firing of A10 dopaminergic neurons
Waszczak, B. L., & Walters, J. R. (1980) · European Journal of Pharmacology · doi:10.1016/0014-2999(80)90308-8 · Cited by 67 · see citing works
SK Ca2+-activated K+ channel ligands alter the firing pattern of dopamine-containing neurons in vivo
Ji, H., & Shepard, D. S. (2006) · Neuroscience · doi:10.1016/j.neuroscience.2006.02.020 · Cited by 65 · see citing works
Self-citationEvidence for a non-GABAergic action of quaternary salts of bicuculline on dopaminergic neurones
Seutin, V., Scuvée-Moreau, J., & Dresse, A. (1997) · Neuropharmacology · doi:10.1016/s0028-3908(97)00147-0 · Cited by 64 · see citing works
Kalén, P., Pritzel, M., Nieoullon, A. L., & Wiklund, L. (1986) · Neuroscience Letters · doi:10.1016/0304-3940(86)90225-9 · Cited by 57 · see citing works
Ping, H., & Shepard, P. D. (1999) · Journal of Neurophysiology · doi:10.1152/jn.1999.81.3.977 · Cited by 41 · see citing works
Self-citationGernert, M., Fedrowitz, M., Właź, P., & Löscher, W. (2004) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2004.03699.x · Cited by 40 · see citing works
Park, M. R. (1987) · Brain Research Bulletin · doi:10.1016/0361-9230(87)90075-x · Cited by 40 · see citing works
Waszczak, B. L., Lee, E. K., Ferraro, T. N., Hare, T. A., & Walters, J. R. (1984) · Brain Research · doi:10.1016/0006-8993(84)90380-9 · Cited by 37 · see citing works
Emson, P. C., Cuello, A. C., Paxinos, G., Jessell, T. M., & Ll, I. (1977) · PubMed · Cited by 37 · see citing works
Efferent Connections of the Habenular Nuclei in the Rat
Herkenham, M. A., & Nauta, W. J. H. (1979) · Birkhäuser Boston eBooks · doi:10.1007/978-1-4684-7920-1_17 · Cited by 30 · see citing works
Lateral Habenular Influence on Dorsal Raphe Neurons
Ferraro, G. (1996) · Brain Research Bulletin · doi:10.1016/s0361-9230(96)00170-0 · Cited by 4 · see citing works
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The reward circuit: linking primate anatomy and human imaging
Haber, S. N., & Knutson, B. (2010) · Neuropsychopharmacology · doi:10.1038/npp.2009.129 · Cited by 3,718 · see citing works
Dopamine in motivational control: rewarding, aversive, and alerting
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
The brain on drugs: from reward to addiction
Volkow, N. D., & Morales, M. (2015) · Cell · doi:10.1016/j.cell.2015.07.046 · Cited by 1,306 · see citing works
Input-specific control of reward and aversion in the ventral tegmental area
Lammel, S., Lim, B. K., Ran, C., Huang, K. W., Betley, M. J., Tye, K. M., Deisseroth, K., & Malenka, R. C. (2012) · Nature · doi:10.1038/nature11527 · Cited by 1,300 · see citing works
Dysregulation of the dopamine system in the pathophysiology of schizophrenia and depression
Grace, A. A. (2016) · Nature Reviews Neuroscience · doi:10.1038/nrn.2016.57 · Cited by 1,166 · see citing works
Mechanisms of ketamine action as an antidepressant
Zanos, P., & Gould, T. D. (2018) · Molecular Psychiatry · doi:10.1038/mp.2017.255 · Cited by 1,127 · see citing works
Neuronal Reward and Decision Signals: From Theories to Data
Schultz, W. (2015) · Physiological Reviews · doi:10.1152/physrev.00023.2014 · Cited by 1,126 · see citing works
Dopamine reward prediction-error signalling: A two-component response
Schultz, W. (2016) · Nature Reviews Neuroscience · doi:10.1038/nrn.2015.26 · Cited by 1,036 · see citing works
Cortico-Basal Ganglia Reward Network: Microcircuitry
Sesack, S. R., & Grace, A. A. (2010) · Neuropsychopharmacology · doi:10.1038/npp.2009.93 · Cited by 985 · see citing works
The habenula: from stress evasion to value-based decision-making
Hikosaka, O. (2010) · Nature Reviews Neuroscience · doi:10.1038/nrn2866 · Cited by 955 · 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
Jhou, T. C., Fields, H. L., Baxter, M. G., Saper, C. B., & Holland, P. C. (2009) · Neuron · doi:10.1016/j.neuron.2009.02.001 · Cited by 696 · see citing works
GABA Neurons of the VTA Drive Conditioned Place Aversion
Tan, K. R., Yvon, C., Turiault, M., Mirzabekov, J. J., Doehner, J., Labouèbe, G., Deisseroth, K. A., Tye, K. M., & Lüscher, C. (2012) · Neuron · doi:10.1016/j.neuron.2012.02.015 · Cited by 635 · see citing works
Neurophysiology of performance monitoring and adaptive behavior
Ullsperger, M., Danielmeier, C., & Jocham, G. (2014) · Physiological Reviews · doi:10.1152/physrev.00041.2012 · Cited by 634 · see citing works
Synaptic potentiation onto habenula neurons in the learned helplessness model of depression
Li, B., Piriz, J., Mirrione, M., Chung, C., Proulx, C. D., Schulz, D., Henn, F., & Malinow, R. (2011) · Nature · doi:10.1038/nature09742 · Cited by 634 · see citing works
Activation of lateral habenula inputs to the ventral midbrain promotes behavioral avoidance
Stamatakis, A. M., & Stuber, G. D. (2012) · Nature Neuroscience · doi:10.1038/nn.3145 · Cited by 564 · see citing works
Representation of negative motivational value in the primate lateral habenula
Matsumoto, M., & Hikosaka, O. (2009) · Nature Neuroscience · doi:10.1038/nn.2233 · Cited by 547 · see citing works
A high-resolution probabilistic in vivo atlas of human subcortical brain nuclei
Pauli, W. M., Nili, A. N., & Tyszka, J. M. (2018) · Scientific Data · doi:10.1038/sdata.2018.63 · Cited by 505 · see citing works
Jhou, T. C., Geisler, S., Marinelli, M., Degarmo, B. A., & Zahm, D. S. (2009) · Journal of Comparative Neurology · doi:10.1002/cne.21891 · Cited by 503 · see citing works
Tripp, G., & Wickens, J. R. (2009) · Neuropharmacology · doi:10.1016/j.neuropharm.2009.07.026 · Cited by 492 · see citing works
Basal Ganglia Disorders Associated with Imbalances in the Striatal Striosome and Matrix Compartments
Crittenden, J. R., & Graybiel, A. M. (2011) · Frontiers in Neuroanatomy · doi:10.3389/fnana.2011.00059 · Cited by 470 · see citing works
Circuits and functions of the lateral habenula in health and in disease
Hu, H., Cui, Y., & Yang, Y. (2020) · Nature reviews. Neuroscience · doi:10.1038/s41583-020-0292-4 · Cited by 471 · see citing works
Habenula: crossroad between the basal ganglia and the limbic system
Hikosaka, O., Sesack, S. R., Lecourtier, L., & Shepard, P. D. (2008) · The Journal of Neuroscience · doi:10.1523/jneurosci.3463-08.2008 · Cited by 432 · see citing works
Self-citationCao, J.-L., Covington, H. E., Friedman, A. K., Wilkinson, M. B., Walsh, J. J., Cooper, D. C., Nestler, E. J., & Han, M.-H. (2010) · The Journal of Neuroscience · doi:10.1523/jneurosci.3177-10.2010 · Cited by 402 · see citing works
Hong, S., Jhou, T. C., Smith, M., Saleem, K. S., & Hikosaka, O. (2011) · The Journal of Neuroscience · doi:10.1523/jneurosci.1384-11.2011 · Cited by 390 · see citing works
The place of dopamine in the cortico-basal ganglia circuit
Haber, S. N. (2014) · Neuroscience · doi:10.1016/j.neuroscience.2014.10.008 · Cited by 364 · see citing works
Reward, addiction, withdrawal to nicotine
De Biasi, M., & Dani, J. A. (2011) · Annual Review of Neuroscience · doi:10.1146/annurev-neuro-061010-113734 · Cited by 366 · see citing works
“Furthermore, electrical stimulation of the LHb inhibits most DA neurons (Christoph et al. 1986, Ji & Shepard 2007, Matsumoto & Hikosaka 2007).”
BackgroundStamatakis, A. M., Jennings, J. H., Ung, R. L., Blair, G. A., Weinberg, R. J., Neve, R. L., Boyce, F., Mattis, J., Ramakrishnan, C., Deisseroth, K., et al. (2013) · Neuron · doi:10.1016/j.neuron.2013.08.023 · Cited by 364 · see citing works
The habenular nuclei: a conserved asymmetric relay station in the vertebrate brain
Bianco, I. H., & Wilson, S. W. (2008) · Philosophical Transactions of the Royal Society B Biological Sciences · doi:10.1098/rstb.2008.0213 · Cited by 344 · see citing works
The globus pallidus sends reward-related signals to the lateral habenula
Hong, S., & Hikosaka, O. (2008) · Neuron · doi:10.1016/j.neuron.2008.09.035 · Cited by 346 · see citing works
Dialogues on prediction errors
Niv, Y., & Schoenbaum, G. M. (2008) · Trends in Cognitive Sciences · doi:10.1016/j.tics.2008.03.006 · Cited by 355 · see citing works
Shabel, S. J., Proulx, C. D., Trias, A., Murphy, R. T., & Malinow, R. (2012) · Neuron · doi:10.1016/j.neuron.2012.02.037 · Cited by 334 · see citing works
Lateral habenula neurons signal errors in the prediction of reward information
Bromberg-Martin, E. S., & Hikosaka, O. (2011) · Nature Neuroscience · doi:10.1038/nn.2902 · Cited by 275 · see citing works
Fujiyama, F., Sohn, J., Nakano, T., Furuta, T., Nakamura, K., Matsuda, W., & Kaneko, T. (2011) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2010.07564.x · Cited by 266 · see citing works
Dandekar, M. P., Fenoy, A. J., Carvalho, A. F., Soares, J. C., & Quevedo, J. (2018) · Molecular Psychiatry · doi:10.1038/mp.2018.2 · Cited by 264 · see citing works
Circuit Mechanisms of Reward, Anhedonia, and Depression
Höflich, A., Michenthaler, P., Kasper, S., & Lanzenberger, R. (2019) · International Journal of Neuropsychopharmacology · doi:10.1093/ijnp/pyy081 · Cited by 253 · see citing works
Lateral habenula projections to dopamine and GABA neurons in the rat ventral tegmental area
Omelchenko, N., Bell, R., & Sesack, S. R. (2009) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2009.06924.x · Cited by 253 · see citing works
Brinschwitz, K., Dittgen, A., Madai, V. I., Lommel, R., Geisler, S., & Veh, R. W. (2010) · Neuroscience · doi:10.1016/j.neuroscience.2010.03.050 · Cited by 240 · see citing works
Balcita‐Pedicino, J. J., Omelchenko, N., Bell, R., & Sesack, S. R. (2010) · The Journal of Comparative Neurology · doi:10.1002/cne.22561 · Cited by 236 · see citing works
Haber, S. N., & Behrens, T. E. J. (2014) · Neuron · doi:10.1016/j.neuron.2014.08.031 · Cited by 230 · see citing works
Reward deficiency and anti-reward in pain chronification
Borsook, D., Linnman, C., Faria, V., Strassman, A. M., Becerra, L. R., & Elman, I. (2016) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2016.05.033 · Cited by 227 · see citing works
Basal ganglia circuit loops, dopamine and motivation: a review and enquiry
Ikemoto, S., Yang, C., & Tan, A. (2015) · Behavioural Brain Research · doi:10.1016/j.bbr.2015.04.018 · Cited by 226 · see citing works
Grady, S. R., Moretti, M., Zoli, M., Marks, M. J., Zanardi, A., Pucci, L., Clementi, F., & Gotti, C. (2009) · The Journal of Neuroscience · doi:10.1523/jneurosci.5121-08.2009 · Cited by 222 · see citing works
Pain and suicidality: Insights from reward and addiction neuroscience
Elman, I., Borsook, D., & Volkow, N. D. (2013) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2013.06.003 · Cited by 220 · see citing works
Smoking, nicotine and neuropsychiatric disorders
Döme, P., Lazáry, J., Kalapos, M. P., & Rihmer, Z. (2009) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2009.07.013 · Cited by 215 · see citing works
Brief optogenetic inhibition of dopamine neurons mimics endogenous negative reward prediction errors
Chang, C. Y., Esber, G. R., Marrero-Garcia, Y., Yau, H., Bonci, A., & Schoenbaum, G. M. (2015) · Nature Neuroscience · doi:10.1038/nn.4191 · Cited by 211 · see citing works
Wallace, M. L., Saunders, A., Huang, K. W., Philson, A. C., Goldman, M., Macosko, E. Z., McCarroll, S. A., & Sabatini, B. L. (2017) · Neuron · doi:10.1016/j.neuron.2017.03.017 · Cited by 205 · see citing works
Jhou, T. C., Good, C. H., Rowley, C. S., Xu, S., Wang, H., Burnham, N. W., Hoffman, A. F., Lupica, C. R., & Ikemoto, S. (2013) · Journal of Neuroscience · doi:10.1523/jneurosci.3634-12.2013 · Cited by 198 · see citing works
The lateral habenula in addiction and depression: an anatomical, synaptic and behavioral overview
Lecca, S., Meye, F. J., & Mameli, M. (2014) · European Journal of Neuroscience · doi:10.1111/ejn.12480 · Cited by 196 · see citing works
Matsui, A., & Williams, J. T. (2011) · Journal of Neuroscience · doi:10.1523/jneurosci.4570-11.2011 · Cited by 191 · see citing works
Surprise! Neural correlates of Pearce–Hall and Rescorla–Wagner coexist within the brain
Roesch, M. R., Esber, G. R., Li, J., Daw, N. D., & Schoenbaum, G. M. (2012) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2011.07986.x · Cited by 186 · see citing works
Reinforcement learning, conditioning, and the brain: Successes and challenges
Maia, T. V. (2009) · Cognitive Affective & Behavioral Neuroscience · doi:10.3758/cabn.9.4.343 · Cited by 184 · see citing works
A Pallidus-Habenula-Dopamine Pathway Signals Inferred Stimulus Values
Bromberg-Martin, E. S., Matsumoto, M., Hong, S., & Hikosaka, O. (2010) · Journal of Neurophysiology · doi:10.1152/jn.00158.2010 · Cited by 182 · see citing works
Lecca, S., Melis, M., Luchicchi, A., Muntoni, A. L., & Pistis, M. (2011) · Neuropsychopharmacology · doi:10.1038/npp.2011.302 · Cited by 185 · see citing works
Stephenson‐Jones, M., Floros, O., Robertson, B., & Grillner, S. E. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1119348109 · Cited by 167 · see citing works
Shifted pallidal co-release of GABA and glutamate in habenula drives cocaine withdrawal and relapse
Meye, F. J., Soiza-Reilly, M., Smit, T., Diana, M. A., Schwarz, M. K., & Mameli, M. (2016) · Nature Neuroscience · doi:10.1038/nn.4334 · Cited by 173 · see citing works
Neuropharmacology of performance monitoring
Jocham, G., & Ullsperger, M. (2008) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2008.08.011 · Cited by 168 · see citing works
Habenula Lesions Reveal that Multiple Mechanisms Underlie Dopamine Prediction Errors
Tian, J., & Uchida, N. (2015) · Neuron · doi:10.1016/j.neuron.2015.08.028 · Cited by 165 · see citing works
Aversive stimuli drive hypothalamus-to-habenula excitation to promote escape behavior
Lecca, S., Meye, F. J., Trusel, M., Tchenio, A., Harris, J., Schwarz, M. K., Burdakov, D., Georges, F., & Mameli, M. (2017) · eLife · doi:10.7554/elife.30697 · Cited by 166 · see citing works
The Lateral Habenula Circuitry: Reward Processing and Cognitive Control
Baker, P. M., Jhou, T. C., Li, B., Matsumoto, M., Mizumori, S. J. Y., Stephenson‐Jones, M., & Vicentic, A. (2016) · Journal of Neuroscience · doi:10.1523/jneurosci.2350-16.2016 · Cited by 156 · see citing works
Schultz, W., Stauffer, W. R., & Lak, A. (2017) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2017.03.013 · Cited by 164 · see citing works
Lecca, S., Melis, M., Luchicchi, A., Ennas, M. G., Castelli, M. P., Muntoni, A. L., & Pistis, M. (2010) · Neuropsychopharmacology · doi:10.1038/npp.2010.190 · 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
Wichmann, T., & DeLong, M. R. (2016) · Neurotherapeutics · doi:10.1007/s13311-016-0426-6 · Cited by 154 · see citing works
Orsini, C. A., Moorman, D. E., Young, J. W., Setlow, B., & Floresco, S. B. (2015) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2015.04.009 · Cited by 153 · see citing works
Dopamine and addiction: what have we learned from 40 years of research
Solinas, M., Belujon, P., Fernagut, P., Jaber, M., & Thiriet, N. (2018) · Journal of Neural Transmission · doi:10.1007/s00702-018-1957-2 · Cited by 155 · see citing works
The Lateral Habenula:No Longer Neglected
Geisler, S., & Trimble, M. (2008) · CNS Spectrums · doi:10.1017/s1092852900016710 · Cited by 149 · see citing works
Distinct Tonic and Phasic Anticipatory Activity in Lateral Habenula and Dopamine Neurons
Bromberg-Martin, E. S., Matsumoto, M., & Hikosaka, O. (2010) · Neuron · doi:10.1016/j.neuron.2010.06.016 · Cited by 146 · see citing works
Friedman, A., Lax, E., Dikshtein, Y., Abraham, L., Flaumenhaft, Y., Sudai, E., Ben‐Tzion, M., Ami-Ad, L., Yaka, R., & Yadid, G. (2010) · Neuropharmacology · doi:10.1016/j.neuropharm.2010.06.008 · Cited by 145 · see citing works
Negative learning bias is associated with risk aversion in a genetic animal model of depression
Shabel, S. J., Murphy, R. T., & Malinow, R. (2014) · Frontiers in Human Neuroscience · doi:10.3389/fnhum.2014.00001 · Cited by 148 · see citing works
Independent circuits in the basal ganglia for the evaluation and selection of actions
Stephenson‐Jones, M., Kardamakis, A. A., Robertson, B., & Grillner, S. E. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1314815110 · Cited by 141 · see citing works
Functional connectivity mapping of regions associated with self‐ and other‐processing
Murray, R. J., Debbané, M., Fox, P. T., Bzdok, D., & Eickhoff, S. B. (2014) · Human Brain Mapping · doi:10.1002/hbm.22703 · Cited by 145 · see citing works
New insights on the subcortical representation of reward
Hikosaka, O., Bromberg-Martin, E. S., Hong, S., & Matsumoto, M. (2008) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2008.07.002 · Cited by 141 · see citing works
Emerging role of CaMKII in neuropsychiatric disease
Robison, A. J. (2014) · Trends in Neurosciences · doi:10.1016/j.tins.2014.07.001 · Cited by 142 · see citing works
Glial Dysfunction in the Mouse Habenula Causes Depressive-Like Behaviors and Sleep Disturbance
Cui, W., Mizukami, H., Yanagisawa, M., Aida, T., Nomura, M., Isomura, Y., Takayanagi, R., Ozawa, K., Tanaka, K., & Aizawa, H. (2014) · The Journal of Neuroscience · doi:10.1523/jneurosci.1465-14.2014 · Cited by 139 · see citing works
Learning shapes the aversion and reward responses of lateral habenula neurons
Wang, D., Li, Y., Feng, Q., Guo, Q., Zhou, J., & Luo, M. (2017) · eLife · doi:10.7554/elife.23045 · Cited by 141 · see citing works
Overriding Phasic Dopamine Signals Redirects Action Selection during Risk/Reward Decision Making
Stopper, C. M., Tse, M. T. L., Montes, D. R., Wiedman, C. R., & Floresco, S. B. (2014) · Neuron · doi:10.1016/j.neuron.2014.08.033 · Cited by 136 · see citing works
Deep brain stimulation for treatment-resistant depression: Efficacy, safety and mechanisms of action
Anderson, R. J., Frye, M. A., Abulseoud, O. A., Lee, K. H., McGillivray, J., Berk, M., & Tye, S. J. (2012) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2012.06.001 · Cited by 137 · see citing works
Gonçalves, L., Sego, C., & Metzger, M. (2011) · The Journal of Comparative Neurology · doi:10.1002/cne.22787 · Cited by 134 · see citing works
Kim, U., & Lee, T. (2012) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2012.08030.x · Cited by 133 · see citing works
What's better for me? Fundamental role for lateral habenula in promoting subjective decision biases
Stopper, C. M., & Floresco, S. (2013) · Nature Neuroscience · doi:10.1038/nn.3587 · Cited by 129 · see citing works
Hendrickson, L. M., Guildford, M. J., & Tapper, A. R. (2013) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2013.00029 · Cited by 132 · see citing works
Unmasking the mysteries of the habenula in pain and analgesia
Shelton, L., Becerra, L. R., & Borsook, D. (2012) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2012.01.004 · Cited by 128 · see citing works
Electric foot shock stress: a useful tool in neuropsychiatric studies
Bali, A., & Jaggi, A. S. (2015) · Reviews in the Neurosciences · doi:10.1515/revneuro-2015-0015 · Cited by 127 · see citing works
Sego, 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
The Origins and Organization of Vertebrate Pavlovian ConditioningPreprint
Fanselow, M., & Wassum, K. (2015) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a021717 · Cited by 123 · see citing works
Functional implications of glutamatergic projections to the ventral tegmental area
Geisler, S., & Wise, R. A. (2008) · Reviews in the Neurosciences · doi:10.1515/revneuro.2008.19.4-5.227 · Cited by 125 · see citing works
Defining the habenula in human neuroimaging studies
Lawson, R. P., Drevets, W. C., & Roiser, J. P. (2012) · NeuroImage · doi:10.1016/j.neuroimage.2012.08.076 · Cited by 125 · see citing works
Lecourtier, L., Oranburg, T. D., & Moghaddam, B. (2008) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2008.06130.x · Cited by 125 · see citing works
The Effects of Tryptophan Depletion on Neural Responses to Emotional Words in Remitted Depression
Roiser, J. P., Levy, J., Fromm, S. J., Nugent, A. C., Talagala, S. L., Hasler, G., Henn, F. A., Sahakian, B. J., & Drevets, W. C. (2009) · Biological Psychiatry · doi:10.1016/j.biopsych.2009.05.002 · Cited by 123 · see citing works
Distinct Midbrain and Habenula Pathways Are Involved in Processing Aversive Events in Humans
Hennigan, K., D’Ardenne, K., & McClure, S. M. (2015) · Journal of Neuroscience · doi:10.1523/jneurosci.0927-14.2015 · Cited by 119 · see citing works
A glass full of optimism: Enrichment effects on cognitive bias in a rat model of depression
Richter, S. H., Schick, A., Hoyer, C., Lankisch, K., Gass, P., & Vollmayr, B. (2012) · Cognitive Affective & Behavioral Neuroscience · doi:10.3758/s13415-012-0101-2 · Cited by 123 · see citing works
The neural underpinnings of cognitive flexibility and their disruption in psychotic illness
Waltz, J. A. (2017) · Neuroscience · doi:10.1016/j.neuroscience.2016.06.005 · Cited by 122 · see citing works
The molecular pathophysiology of depression and the new therapeutics
Tian, H., Hu, Z., Xu, J., & Wang, C. (2022) · MedComm · doi:10.1002/mco2.156 · Cited by 122 · see citing works
New therapeutic opportunities for 5-HT2C receptor ligands in neuropsychiatric disorders
Giovanni, G. D., & Deurwaerdère, P. D. (2015) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2015.11.009 · Cited by 121 · see citing works
Wang, D. V., & Tsien, J. Z. (2011) · PLoS ONE · doi:10.1371/journal.pone.0017047 · Cited by 116 · see citing works
Takahashi, Y. K. (2008) · Frontiers in Neuroscience · doi:10.3389/neuro.01.014.2008 · Cited by 115 · 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
Handbook of Basal Ganglia Structure and Function
(2016) · Handbook of behavioral neuroscience · doi:10.1016/b978-0-12-802206-1.00052-0 · Cited by 118 · see citing works
Anatomical and single-cell transcriptional profiling of the murine habenular complex
Wallace, M. L., Huang, K. W., Hochbaum, D., Hyun, M., Radeljic, G., & Sabatini, B. L. (2020) · eLife · doi:10.7554/elife.51271 · Cited by 113 · see citing works
- Authors
- Ji, H., & Shepard, P. D.
- Affiliations
- University of Maryland, Baltimore (US)
- Venue
- Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2007-06-27
- Volume
- 27
- Issue
- 26
- Pages
- 6923-6930
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC6672239
- OpenAlex
- W2014239075
- Cited by
- 388
- References
- 65
- Citations by year
- 2026: 11 · 2025: 8 · 2024: 15 · 2023: 15 · 2022: 16 · 2021: 19 · 2020: 15 · 2019: 15 · 2018: 29 · 2017: 25 · 2016: 34 · 2015: 22 · 2014: 23 · 2013: 28 · 2012: 24
- FWCI
- 8.10
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Neuroscience (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- U.S. Public Health Service
- National Institute of Mental Health (MH-072647, R24MH072647)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Keywords
- lateral habenula, dopaminergic neurons, GABAA receptor, substantia nigra, ventral tegmental area, fasciculus retroflexus, reward expectancy, error signal, bicuculline, apamin, GABAergic neurons, midbrain dopamine, single-pulse stimulation
- MeSH terms
- Animals, Dopamine, Electric Stimulation, gamma-Aminobutyric Acid, Male, Mesencephalon, Neural Inhibition, Neural Pathways, Synaptic Transmission, Neurons, Receptors, GABA-A, Reward, Substantia Nigra, Rats, Sprague-Dawley, Ventral Tegmental Area, GABA Antagonists, Habenula, Potassium Channel Blockers, Rats
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