Convergent Processing of Both Positive and Negative Motivational Signals by the VTA Dopamine Neuronal Populations
Open accessAbstract
Dopamine neurons in the ventral tegmental area (VTA) have been traditionally studied for their roles in reward-related motivation or drug addiction. Here we study how the VTA dopamine neuron population may process fearful and negative experiences as well as reward information in freely behaving mice. Using multi-tetrode recording, we find that up to 89% of the putative dopamine neurons in the VTA exhibit significant activation in response to the conditioned tone that predict food reward, while the same dopamine neuron population also respond to the fearful experiences such as free fall and shake events. The majority of these VTA putative dopamine neurons exhibit suppression and offset-rebound excitation, whereas ∼25% of the recorded putative dopamine neurons show excitation by the fearful events. Importantly, VTA putative dopamine neurons exhibit parametric encoding properties: their firing change durations are proportional to the fearful event durations. In addition, we demonstrate that the contextual information is crucial for these neurons to respectively elicit positive or negative motivational responses by the same conditioned tone. Taken together, our findings suggest that VTA dopamine neurons may employ the convergent encoding strategy for processing both positive and negative experiences, intimately integrating with cues and environmental context.
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Acute stressors are encoded by dopamine-releasing neurons in the VTA, cause dopamine sensitization in the nucleus accumbens, and facilitate drug taking; mesolimbic dopamine release also encodes negative motivational states and stress responses.
“Recent experiments also show that acute stressors are encoded by DA-releasing neurons in the VTA, cause DA sensitization in the NAC, and facilitate drug taking; demonstrating that mesolimbic DA release also encodes negative motivational states and stress responses (Miczek et al 2011; Wang and Tsien 2011).”
From The behavioral, anatomical and pharmacological parallels between social attachment, love and addiction (2012) · cites this paper as Wang and Tsien 2011
Some stress-related effects of CRF in the NAC shell may be DA-dependent.
“Some of the stress-related effects of CRF in the NAC shell may be DA-dependent; recall that DA is also modulated by acute and chronic stressors (Miczek et al 2011; Wang and Tsien 2011; Chen et al 2012b).”
From The behavioral, anatomical and pharmacological parallels between social attachment, love and addiction (2012) · cites this paper as Wang and Tsien 2011
In freely behaving mice, VTA dopaminergic neurons can exhibit responses to different valences; 89% respond with activation to a conditioned reward, they also respond to fearful events with the majority showing suppression, and 25% respond with excitation to both positive and fearful events.
“Thus, although 89% of VTA dopaminergic neurons respond with activation to a conditioned reward, they also respond to fearful events, with the majority of the neurons showing suppression. Interestingly, 25% respond with excitation to both positive and fearful events [101].”
From A neoHebbian framework for episodic memory; role of dopamine-dependent late LTP (2011) · cites this paper as [101]
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Cites
The Mouse Brain in Stereotaxic Coordinates
Paxinos, G. (2001) · Cited by 12,859 · see citing works
Di Chiara, G., & Imperato, A. (1988) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.85.14.5274 · Cited by 4,733 · see citing works
What is the role of dopamine in reward: hedonic impact, reward learning, or incentive salience?
Berridge, K. C., & Robinson, T. E. (1998) · Brain Research Reviews · doi:10.1016/s0165-0173(98)00019-8 · Cited by 4,127 · see citing works
Neural systems of reinforcement for drug addiction: from actions to habits to compulsion
Everitt, B. J., & Robbins, T. W. (2005) · Nature Neuroscience · doi:10.1038/nn1579 · Cited by 3,785 · see citing works
Dopamine, learning and motivation.
Wise, R. A. (2004) · Nature Reviews Neuroscience · doi:10.1038/nrn1406 · Cited by 3,379 · see citing works
NEURAL MECHANISMS OF ADDICTION: The Role of Reward-Related Learning and Memory
Hyman, S. E., Malenka, R. C., & Nestler, E. J. (2006) · Annual Review of Neuroscience · doi:10.1146/annurev.neuro.29.051605.113009 · Cited by 2,647 · see citing works
The debate over dopamine’s role in reward: the case for incentive salience
Berridge, K. C. (2007) · Psychopharmacology · doi:10.1007/s00213-006-0578-x · Cited by 2,347 · see citing works
The hippocampal-VTA loop: controlling the entry of information into long-term memory
Lisman, J. E., & Grace, A. A. (2005) · Neuron · doi:10.1016/j.neuron.2005.05.002 · Cited by 1,983 · see citing works
An opponent-process theory of motivation. I. Temporal dynamics of affect
Solomon, R. L., & Corbit, J. D. (1974) · Psychological Review · doi:10.1037/h0036128 · Cited by 1,704 · see citing works
Ikemoto, S., & Panksepp, J. (1999) · Brain Research Reviews · doi:10.1016/s0165-0173(99)00023-5 · Cited by 1,450 · see citing works
Multiple dopamine functions at different time courses
Schultz, W. (2007) · Annual Review of Neuroscience · doi:10.1146/annurev.neuro.28.061604.135722 · Cited by 1,415 · see citing works
Two types of dopamine neuron distinctly convey positive and negative motivational signals
Matsumoto, M., & Hikosaka, O. (2009) · Nature · doi:10.1038/nature08028 · Cited by 1,378 · 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
Midbrain dopamine neurons encode a quantitative reward prediction error signal
Bayer, H. M., & Glimcher, P. W. (2005) · Neuron · doi:10.1016/j.neuron.2005.05.020 · Cited by 1,304 · 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
Adaptive Coding of Reward Value by Dopamine Neurons
Tobler, P. N., Fiorillo, C. D., & Schultz, W. (2005) · Science · doi:10.1126/science.1105370 · Cited by 1,276 · see citing works
Unique properties of mesoprefrontal neurons within a dual mesocorticolimbic dopamine system
Lammel, S., Hetzel, A., Häckel, O., Jones, I., Liss, B., & Roeper, J. (2008) · Neuron · doi:10.1016/j.neuron.2008.01.022 · Cited by 976 · see citing works
Carr, D. B., & Sesack, S. R. (2000) · Journal of Neuroscience · doi:10.1523/jneurosci.20-10-03864.2000 · Cited by 880 · see citing works
Preferential activation of midbrain dopamine neurons by appetitive rather than aversive stimuli
Mirenowicz, J., & Schultz, W. (1996) · Nature · doi:10.1038/379449a0 · Cited by 829 · see citing works
Phasic excitation of dopamine neurons in ventral VTA by noxious stimuli
Brischoux, F., Chakraborty, S., Brierley, D. I., & Ungless, M. A. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0811507106 · Cited by 801 · 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
Ventral Tegmental Area Neurons in Learned Appetitive Behavior and Positive Reinforcement
Fields, H. L., Hjelmstad, G. O., Margolis, E. B., & Nicola, S. M. (2007) · Annual Review of Neuroscience · doi:10.1146/annurev.neuro.30.051606.094341 · Cited by 611 · see citing works
Roesch, M. R., Calu, D. J., & Schoenbaum, G. (2007) · Nature Neuroscience · doi:10.1038/nn2013 · Cited by 597 · see citing works
Baliki, M. N., Geha, P., Fields, H. L., & Apkarian, A. V. (2010) · Neuron · doi:10.1016/j.neuron.2010.03.002 · Cited by 549 · see citing works
Mesolimbic dopaminergic pathways in fear conditioning
Pezze, M. A., & Feldon, J. (2004) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2004.09.004 · Cited by 510 · 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
Firing modes of midbrain dopamine cells in the freely moving rat
Hyland, B. I., Reynolds, J. N. J., HAY, J. G., Perk, C. G., & Miller, R. (2002) · Neuroscience · doi:10.1016/s0306-4522(02)00267-1 · Cited by 487 · see citing works
An Opponent-Process Theory of Motivation
Solomon, R. L., & Corbit, J. D. (2008) · Cited by 461 · see citing works
Opponent appetitive-aversive neural processes underlie predictive learning of pain relief
Seymour, B., O'Doherty, J. P., Koltzenburg, M., Wiech, K., Frackowiak, R., Friston, K., & Dolan, R. (2005) · Nature Neuroscience · doi:10.1038/nn1527 · Cited by 439 · 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
Ji, H., & Shepard, P. D. (2007) · Journal of Neuroscience · doi:10.1523/jneurosci.0958-07.2007 · Cited by 388 · see citing works
Karreman, M., & Moghaddam, B. (1996) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.1996.66020589.x · Cited by 357 · see citing works
Real-time chemical responses in the nucleus accumbens differentiate rewarding and aversive stimuli
Roitman, M. F., Wheeler, R. A., Wightman, R. M., & Carelli, R. M. (2008) · Nature Neuroscience · doi:10.1038/nn.2219 · Cited by 343 · see citing works
Diana, M., Pistis, M., Carboni, S., Gessa, G. L., & Rossetti, Z. L. (1993) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.90.17.7966 · Cited by 309 · see citing works
L-DOPA Disrupts Activity in the Nucleus Accumbens during Reversal Learning in Parkinson's Disease
Cools, R., Lewis, S. J. G., Clark, L., Barker, R. A., & Robbins, T. W. (2006) · Neuropsychopharmacology · doi:10.1038/sj.npp.1301153 · Cited by 284 · 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
Joshua, M., Adler, A., Mitelman, R., Vaadia, E., & Bergman, H. (2008) · The Journal of Neuroscience · doi:10.1523/jneurosci.3839-08.2008 · Cited by 273 · see citing works
Miller, J. D., Farber, J., Gatz, P., Roffwarg, H. P., & German, D. C. (1983) · Brain Research · doi:10.1016/0006-8993(83)91101-0 · Cited by 269 · see citing works
Coupled Oscillator Model of the Dopaminergic Neuron of the Substantia Nigra
Wilson, C. J., & Callaway, J. C. (2000) · Journal of Neurophysiology · doi:10.1152/jn.2000.83.5.3084 · Cited by 261 · see citing works
Margolis, E. B., Mitchell, J., Ishikawa, J., Hjelmstad, G. O., & Fields, H. L. (2008) · Journal of Neuroscience · doi:10.1523/jneurosci.1526-08.2008 · Cited by 232 · see citing works
Depaulis, A., Keay, K. A., & Bandler, R. J. (1992) · Experimental Brain Research · doi:10.1007/bf00227243 · Cited by 212 · see citing works
Guarraci, F. A., & Kapp, B. S. (1999) · Behavioural Brain Research · doi:10.1016/s0166-4328(98)00102-8 · Cited by 201 · see citing works
Ventura, R., Morrone, C., & Puglisi‐Allegra, S. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0610178104 · Cited by 190 · see citing works
Lin, L., Osan, R. M., Shoham, S., Jin, W., Zuo, W., & Tsien, J. Z. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0408233102 · Cited by 117 · see citing works
Self-citationThe dynamics of dopamine in control of motor behavior
Joshua, M., Adler, A., & Bergman, H. (2009) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2009.10.001 · Cited by 109 · see citing works
Lee, R., Steffensen, S. C., & Henriksen, S. J. (2001) · Journal of Neuroscience · doi:10.1523/jneurosci.21-05-01757.2001 · Cited by 109 · see citing works
Large-scale neural ensemble recording in the brains of freely behaving mice
Lin, L., Chen, G., Xie, K., Zaia, K. A., Zhang, S., & Tsien, J. Z. (2006) · Journal of Neuroscience Methods · doi:10.1016/j.jneumeth.2005.12.032 · Cited by 108 · see citing works
Self-citationKiyatkin, E. A., & Rebec, G. V. (1998) · Neuroscience · doi:10.1016/s0306-4522(98)00054-2 · Cited by 107 · see citing works
Synchronization of Midbrain Dopaminergic Neurons Is Enhanced by Rewarding Events
Joshua, M., Adler, A., Prut, Y., Vaadia, E., Wickens, J. R., & Bergman, H. (2009) · Neuron · doi:10.1016/j.neuron.2009.04.026 · Cited by 87 · see citing works
Nucleus accumbens dopamine and learned fear revisited: a review and some new findings
Levita, L., Dalley, J. W., & Robbins, T. W. (2002) · Behavioural Brain Research · doi:10.1016/s0166-4328(02)00287-5 · Cited by 82 · see citing works
Methods for Studying Functional Interactions Among Neuronal Populations
Narayanan, N. S., & Laubach, M. (2008) · Methods in molecular biology · doi:10.1007/978-1-59745-543-5_7 · Cited by 54 · see citing works
Electrical Coupling Between Model Midbrain Dopamine Neurons: Effects on Firing Pattern and Synchrony
Komendantov, A. O., & Canavier, C. C. (2002) · Journal of Neurophysiology · doi:10.1152/jn.00255.2001 · Cited by 42 · see citing works
Do Substantia Nigra Dopaminergic Neurons Differentiate Between Reward and Punishment?
Frank, M., & Surmeier, D. J. (2009) · Journal of Molecular Cell Biology · doi:10.1093/jmcb/mjp010 · Cited by 11 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Updating dopamine reward signals
Schultz, W. (2013) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2012.11.012 · Cited by 651 · see citing works
A 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
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
Burkett, J. P., & Young, L. J. (2012) · Psychopharmacology · doi:10.1007/s00213-012-2794-x · Cited by 307 · see citing works
“experiments also show that acute stressors are encoded by DA-releasing neurons in the ventral tegmental area (VTA), cause DA sensitization in the NAC, and facilitate drug taking, demonstrating that mesolimbic DA release also encodes negative motivational states and stress responses (Miczek et al. 2011; Wang and Tsien…”
InfluentialNeuronal circuits underlying acute morphine action on dopamine neurons
Jalabert, M., Bourdy, R., Courtin, J., Veinante, P., Manzoni, O. J., Barrot, M., & Georges, F. E. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1105418108 · Cited by 302 · see citing works
Badrinarayan, A., Wescott, S. A., Vander Weele, C. M., Saunders, B. T., Couturier, B. E., Maren, S., & Aragona, B. J. (2012) · The Journal of Neuroscience · doi:10.1523/jneurosci.3557-12.2012 · Cited by 225 · see citing works
A VTA GABAergic Neural Circuit Mediates Visually Evoked Innate Defensive Responses
Zhou, Z., Liu, X., Chen, S., Zhang, Z., Liu, Y., Montardy, Q., Tang, Y., Wei, P., Liu, N., Li, L., et al. (2019) · Neuron · doi:10.1016/j.neuron.2019.05.027 · Cited by 211 · see citing works
Two Dimensions of Value: Dopamine Neurons Represent Reward But Not Aversiveness
Fiorillo, C. D. (2013) · Science · doi:10.1126/science.1238699 · Cited by 203 · 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
Aversive stimulus differentially triggers subsecond dopamine release in reward regions
Budygin, E. A., Park, J., Bass, C. E., Grinevich, V. P., Bonin, K. D., & Wightman, R. M. (2012) · Neuroscience · doi:10.1016/j.neuroscience.2011.10.056 · Cited by 152 · see citing works
Encoding of Aversion by Dopamine and the Nucleus Accumbens
McCutcheon, J. E., Ebner, S. R., Loriaux, A. L., & Roitman, M. F. (2012) · Frontiers in Neuroscience · doi:10.3389/fnins.2012.00137 · Cited by 146 · see citing works
Behavioural and dopaminergic signatures of resilience
Willmore, L., Cameron, C., Yang, J., Witten, I. B., & Falkner, A. L. (2022) · Nature · doi:10.1038/s41586-022-05328-2 · Cited by 144 · see citing works
Heterogeneity of dopamine neuron activity across traits and states
Marinelli, M., & McCutcheon, J. E. (2014) · Neuroscience · doi:10.1016/j.neuroscience.2014.07.034 · Cited by 141 · see citing works
Stress responses and the mesolimbic dopamine system: Social contexts and sex differences
Trainor, B. C. (2011) · Hormones and Behavior · doi:10.1016/j.yhbeh.2011.08.013 · Cited by 138 · see citing works
Beyond reward prediction errors: the role of dopamine in movement kinematics
Barter, J. W., Li, S., Lu, D., Bartholomew, R. A., Rossi, M. A., Shoemaker, C. T., Salas-Meza, D., Gaidis, E., & Yin, H. H. (2015) · Frontiers in Integrative Neuroscience · doi:10.3389/fnint.2015.00039 · Cited by 137 · see citing works
Wenzel, J. M., Rauscher, N. A., Cheer, J. F., & Oleson, E. B. (2015) · ACS Chemical Neuroscience · doi:10.1021/cn500255p · Cited by 131 · see citing works
Role of nicotinic acetylcholine receptors in regulating dopamine neuron activity
Faure, P., Tolu, S., Valverde, S., & Naudé, J. (2014) · Neuroscience · doi:10.1016/j.neuroscience.2014.05.040 · Cited by 125 · see citing works
NMDA Receptors in Dopaminergic Neurons Are Crucial for Habit Learning
Wang, L. P., Li, F. R., Wang, D., Xie, K., Wang, D., Shen, X., & Tsien, J. Z. (2011) · Neuron · doi:10.1016/j.neuron.2011.10.019 · Cited by 122 · see citing works
Self-citationFunctional Dissection of Basal Ganglia Inhibitory Inputs onto Substantia Nigra Dopaminergic Neurons
Evans, R. C., Twedell, E. L., Zhu, M., Ascencio, J., Zhang, R., & Khaliq, Z. M. (2020) · Cell Reports · doi:10.1016/j.celrep.2020.108156 · Cited by 109 · see citing works
Dopamine Neurons Reflect the Uncertainty in Fear Generalization
Jo, Y. S., Heymann, G., & Zweifel, L. S. (2018) · Neuron · doi:10.1016/j.neuron.2018.09.028 · Cited by 107 · see citing works
Cai, L. X., Pizano, K., Gundersen, G. W., Hayes, C. L., Fleming, W., Holt, S., Cox, J., & Witten, I. B. (2020) · eLife · doi:10.7554/elife.54936 · Cited by 104 · see citing works
Diversity and Homogeneity in Responses of Midbrain Dopamine Neurons
Fiorillo, C. D., Yun, S. R., & Song, M. R. (2013) · The Journal of Neuroscience · doi:10.1523/jneurosci.3886-12.2013 · Cited by 99 · see citing works
Fiorillo, C. D., Song, M. R., & Yun, S. R. (2013) · The Journal of Neuroscience · doi:10.1523/jneurosci.3883-12.2013 · Cited by 98 · see citing works
A comparison of neural responses to appetitive and aversive stimuli in humans and other mammals
Hayes, D. J., Duncan, N. W., Xu, J., & Northoff, G. (2014) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2014.06.018 · Cited by 98 · see citing works
Melis, M., Scheggi, S., Carta, G., Madeddu, C., Lecca, S., Luchicchi, A., Cadeddu, F., Frau, R., Fattore, L., Fadda, P., et al. (2013) · Journal of Neuroscience · doi:10.1523/jneurosci.4647-12.2013 · Cited by 94 · see citing works
Tsetsenis, T., Badyna, J. K., Wilson, J., Zhang, X., Krizman, E. N., Subramaniyan, M., Yang, K., THOMAS, S. A., & Dani, J. A. (2021) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2111069118 · Cited by 83 · see citing works
Brown, P. L., & Shepard, P. D. (2016) · Journal of Neurophysiology · doi:10.1152/jn.00305.2016 · Cited by 75 · see citing works
Habit learning and memory in mammals: Behavioral and neural characteristics
Gasbarri, A., Pompili, A., Packard, M. G., & Tomaz, C. A. B. (2014) · Neurobiology of Learning and Memory · doi:10.1016/j.nlm.2014.06.010 · Cited by 72 · see citing works
Prefrontal/accumbal catecholamine system processes high motivational salience
Puglisi‐Allegra, S., & Ventura, R. (2012) · Frontiers in Behavioral Neuroscience · doi:10.3389/fnbeh.2012.00031 · Cited by 70 · see citing works
Onset and offset of aversive events establish distinct memories requiring fear and reward networksPreprint
Andreatta, M., Fendt, M., Mühlberger, A., Wieser, M. J., Imobersteg, S., Yarali, A., Gerber, B., & Pauli, P. (2012) · Learning & Memory · doi:10.1101/lm.026864.112 · Cited by 67 · see citing works
The Role of Dopamine in Associative Learning in Drosophila: An Updated Unified Model
Adel, M., & Griffith, L. C. (2021) · Neuroscience Bulletin · doi:10.1007/s12264-021-00665-0 · Cited by 64 · see citing works
Dopamine Regulation of Amygdala Inhibitory Circuits for Expression of Learned Fear
Kwon, O.-B., Lee, J. H., Kim, H. J., Lee, S., Lee, S., Jeong, M.-J., Kim, S.-J., Jo, H.-J., Ko, B., Chang, S., et al. (2015) · Neuron · doi:10.1016/j.neuron.2015.09.001 · Cited by 64 · see citing works
Amygdala Circuits for Fear Memory: A Key Role for Dopamine Regulation
Lee, J. H., Lee, S. H., & Kim, J. (2016) · The Neuroscientist · doi:10.1177/1073858416679936 · Cited by 63 · see citing works
Involvement of the Ventral Tegmental Area in a Rodent Model of Post-Traumatic Stress Disorder
Corral-Frías, N. S., Lahood, R. P., Edelman-Vogelsang, K. E., French, E. D., & Fellous, J. (2012) · Neuropsychopharmacology · doi:10.1038/npp.2012.189 · Cited by 58 · see citing works
Seeking motivation and reward: Roles of dopamine, hippocampus, and supramammillo-septal pathway
Kesner, A. J., Calva, C. B., & Ikemoto, S. (2022) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2022.102252 · Cited by 56 · see citing works
van Roekel, E., Vrijen, C., Heininga, V. E., Masselink, M., Bos, E. H., & Oldehinkel, A. J. (2016) · Behavior Therapy · doi:10.1016/j.beth.2016.09.009 · Cited by 52 · see citing works
Ilango, A., Shumake, J., Wetzel, W., Scheich, H., & Ohl, F. W. (2012) · Frontiers in Neuroscience · doi:10.3389/fnins.2012.00132 · Cited by 50 · see citing works
Ilango, A., Kesner, A. J., Broker, C. J., Wang, D. V., & Ikemoto, S. (2014) · Frontiers in Behavioral Neuroscience · doi:10.3389/fnbeh.2014.00155 · Cited by 50 · see citing works
Self-citationGreenberg, G. D., Steinman, M. Q., Doig, I. E., Hao, R., & Trainor, B. C. (2015) · European Journal of Neuroscience · doi:10.1111/ejn.13099 · Cited by 49 · see citing works
Tarfa, R. A., Evans, R. C., & Khaliq, Z. M. (2017) · Journal of Neuroscience · doi:10.1523/jneurosci.2969-16.2017 · Cited by 49 · see citing works
Brown, P. L., & Shepard, P. D. (2013) · PLoS ONE · doi:10.1371/journal.pone.0060678 · Cited by 47 · see citing works
Vega‐Quiroga, I., Yarur, H. E., & Gysling, K. (2017) · Neuropharmacology · doi:10.1016/j.neuropharm.2017.09.034 · Cited by 47 · see citing works
Approach–withdrawal and the role of the striatum in the temperament of behavioral inhibition.
Helfinstein, S. M., Fox, N. A., & Pine, D. S. (2011) · Developmental Psychology · doi:10.1037/a0026402 · Cited by 43 · see citing works
Liu, J., Wei, W., Kuang, H., Tsien, J. Z., & Zhao, F. (2014) · PLoS ONE · doi:10.1371/journal.pone.0093270 · Cited by 40 · see citing works
Self-citationPark, J., Bucher, E. S., Budygin, E. A., & Wightman, R. M. (2015) · Pain · doi:10.1097/01.j.pain.0000460312.79195.ed · Cited by 40 · see citing works
Wang, D. V., Viereckel, T., Zell, V., Konradsson‐Geuken, Å., Broker, C. J., Talishinsky, A., Yoo, J. H., Galinato, M. H., Arvidsson, E., Kesner, A. J., et al. (2017) · Cell Reports · doi:10.1016/j.celrep.2017.02.062 · Cited by 40 · see citing works
Self-citationDopamine Rebound-Excitation Theory: Putting Brakes on PTSD
Lee, J. C., Wang, L. P., & Tsien, J. Z. (2016) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2016.00163 · Cited by 39 · see citing works
Self-citationDombrowski, P. A., Maia, T. V., Boschen, S. L., Bortolanza, M., Wendler, E., Schwarting, R. K. W., Brandão, M. L., Winn, P., Blaha, C. D., & Cunha, C. D. (2012) · Behavioural Brain Research · doi:10.1016/j.bbr.2012.06.031 · Cited by 39 · see citing works
Reinforcement signaling of punishment versus relief in fruit fliesPreprint
König, C., Khalili, A., Ganesan, M., Nishu, A. P., Garza, A. P., Niewalda, T., Gerber, B., Aso, Y., & Yarali, A. (2018) · Learning & Memory · doi:10.1101/lm.047308.118 · Cited by 39 · see citing works
Visualization of plasticity in fear-evoked calcium signals in midbrain dopamine neuronsPreprint
Gore, B. B., Soden, M. E., & Zweifel, L. S. (2014) · Learning & Memory · doi:10.1101/lm.036079.114 · Cited by 38 · see citing works
Xie, K., Kuang, H., & Tsien, J. Z. (2013) · PLoS ONE · doi:10.1371/journal.pone.0064907 · Cited by 35 · see citing works
Self-citationFaget, L. C., Oriol, L., Lee, W.-C., Zell, V., Sargent, C., Flores, A. J., Hollon, N. G., Ramanathan, D., & Hnasko, T. S. (2024) · Nature Communications · doi:10.1038/s41467-024-48340-y · Cited by 35 · see citing works
Bauch, E. M., Rausch, V. H., & Bunzeck, N. (2014) · Human Brain Mapping · doi:10.1002/hbm.22497 · Cited by 34 · see citing works
Vashchinkina, E., Panhelainen, A. E., Aitta‐aho, T., & Korpi, E. R. (2014) · Frontiers in Pharmacology · doi:10.3389/fphar.2014.00256 · Cited by 34 · see citing works
Optogenetic and chemogenetic insights into the food addiction hypothesis
Krashes, M. J., & Kravitz, A. V. (2014) · Frontiers in Behavioral Neuroscience · doi:10.3389/fnbeh.2014.00057 · Cited by 32 · see citing works
Kourosh‐Arami, M., Komaki, A., & Zarrindast, M. (2022) · CNS & Neurological Disorders - Drug Targets · doi:10.2174/1871527321666220418115503 · Cited by 32 · see citing works
Brain Computation Is Organized via Power-of-Two-Based Permutation Logic
Xie, K., Fox, G. E., Liu, J., Lyu, C., Lee, J. C., Kuang, H., Jacobs, S., Li, M., Liu, T., Song, S., et al. (2016) · Frontiers in Systems Neuroscience · doi:10.3389/fnsys.2016.00095 · Cited by 30 · see citing works
Self-citationRole of dopamine D2 receptors in optimizing choice strategy in a dynamic and uncertain environment
Kwak, S., Huh, N., Seo, J.-S., Lee, J.-E., Han, P., & Jung, M. W. (2014) · Frontiers in Behavioral Neuroscience · doi:10.3389/fnbeh.2014.00368 · Cited by 27 · see citing works
On initial Brain Activity Mapping of episodic and semantic memory code in the hippocampus
Tsien, J. Z., Li, M., Osan, R. M., Chen, G., Lin, L., Wang, P. L., Frey, S., Frey, J. U., Zhu, D., Liu, T., et al. (2013) · Neurobiology of Learning and Memory · doi:10.1016/j.nlm.2013.06.019 · Cited by 26 · see citing works
Self-citationQuattrocchi, G., Monaco, J., Ho, A., Irmen, F., Strube, W., Ruge, D., Bestmann, S., & Galea, J. M. (2018) · eNeuro · doi:10.1523/eneuro.0453-17.2018 · Cited by 25 · see citing works
Optical suppression of drug-evoked phasic dopamine release
McCutcheon, J. E., Cone, J. J., Sinon, C. G., Fortin, S. M., Kantak, P. A., Witten, I. B., Deisseroth, K. A., Stuber, G. D., & Roitman, M. F. (2014) · Frontiers in Neural Circuits · doi:10.3389/fncir.2014.00114 · Cited by 25 · see citing works
Almela, P., Zaragoza, J. N., García-Carmona, J. A., Mora, L., Hidalgo, J. M., Milanés, M. V., & Laorden, M. L. (2012) · PLoS ONE · doi:10.1371/journal.pone.0047089 · Cited by 25 · see citing works
Goedhoop, J., Arbab, T., & Willuhn, I. (2023) · The Journal of Neuroscience · doi:10.1523/jneurosci.1527-22.2023 · Cited by 24 · see citing works
Principles of Intelligence: On Evolutionary Logic of the Brain
Tsien, J. Z. (2016) · Frontiers in Systems Neuroscience · doi:10.3389/fnsys.2015.00186 · Cited by 24 · see citing works
Self-citationViral vector-based tools advance knowledge of basal ganglia anatomy and physiology
Sizemore, R. J., Seeger-Armbruster, S., Hughes, S. M., & Parr‐Brownlie, L. C. (2016) · Journal of Neurophysiology · doi:10.1152/jn.01131.2015 · Cited by 23 · see citing works
Ilango, A., Shumake, J., Wetzel, W., Scheich, H., & Ohl, F. W. (2013) · PLoS ONE · doi:10.1371/journal.pone.0065684 · Cited by 19 · see citing works
Computational Classification Approach to Profile Neuron Subtypes from Brain Activity Mapping Data
Li, M., Zhao, F., Lee, J., Wang, D., Kuang, H., & Tsien, J. Z. (2015) · Scientific Reports · doi:10.1038/srep12474 · Cited by 18 · see citing works
Self-citationPadulo, C., Pizzi, S. D., Bonanni, L., Edden, R. A. E., Ferretti, A., Marzoli, D., Franciotti, R., Manippa, V., ONOFRJ, M. C., Sepede, G., et al. (2016) · Neuroscience · doi:10.1016/j.neuroscience.2016.07.010 · Cited by 17 · see citing works
Evans, R. C. (2022) · Neurobiology of Disease · doi:10.1016/j.nbd.2022.105815 · Cited by 16 · see citing works
Sampaio, T. B., de Souza, B. S., Roversi, K., Schuh, T., Poli, A., Takahashi, R. N., & Prediger, R. D. (2019) · Neuropharmacology · doi:10.1016/j.neuropharm.2019.04.006 · Cited by 15 · see citing works
Pleasure: The missing link in the regulation of sleep
Rial, R. V., Cañellas, F., Gamundı́, A., Akaârir, M., & Nicolau, M. C. (2018) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2018.03.012 · Cited by 12 · see citing works
Pan-Vazquez, A., Araujo, Y. S., McMannon, B., Louka, M., Bandi, A., Haetzel, L. M., Faulkner, M., Pillow, J. W., Daw, N. D., & Witten, I. B. (2024) · Current Biology · doi:10.1016/j.cub.2024.09.045 · Cited by 11 · see citing works
Muscarinic Receptor Activation Preferentially Inhibits Rebound in Vulnerable Dopaminergic Neurons
Beaver, M. L., & Evans, R. C. (2025) · Journal of Neuroscience · doi:10.1523/jneurosci.1443-24.2025 · Cited by 11 · see citing works
Enrico, P., Sirca, D., Mereu, M., Peana, A. T., Mercante, B., & Diana, M. (2012) · Drug and Alcohol Dependence · doi:10.1016/j.drugalcdep.2012.06.006 · Cited by 11 · see citing works
Real-Time Accumbal Dopamine Response to Negative Stimuli: Effects of Ethanol
Mikhailova, M. A., Deal, A. L., Grinevich, V. P., Bonin, K., Gainetdinov, R. R., & Budygin, E. A. (2018) · ACS Chemical Neuroscience · doi:10.1021/acschemneuro.8b00272 · Cited by 11 · see citing works
Gerber, B., König, C., Fendt, M., Andreatta, M., Romanos, M., Pauli, P., & Yarali, A. (2019) · Current Opinion in Behavioral Sciences · doi:10.1016/j.cobeha.2018.12.001 · Cited by 11 · see citing works
Fischer, C., Thomas, D., Gurke, R., & Tegeder, I. (2024) · Pflügers Archiv - European Journal of Physiology · doi:10.1007/s00424-024-03012-0 · Cited by 9 · see citing works
Li, M., Xie, K., Kuang, H., Liu, J., Wang, D., Fox, G. E., Wei, W., Li, X., Li, Y., Fang, Z., et al. (2017) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/145813 · Cited by 9 · see citing works
Self-citationUnexpected downshifts in reward magnitude induce variation in human behavior
Jensen, G., Stokes, P. D., Paterniti, A., & Balsam, P. D. (2013) · Psychonomic Bulletin & Review · doi:10.3758/s13423-013-0490-4 · Cited by 8 · see citing works
Do Green Building Standards Meet the Biophilic Design Strategies?
Güngör, B. Ş. (2020) · Journal of Design Studio · doi:10.46474/jds.739849 · Cited by 7 · see citing works
Dopamine, uncertainty, and fear generalization
Zweifel, L. S. (2019) · Current Opinion in Behavioral Sciences · doi:10.1016/j.cobeha.2019.01.003 · Cited by 7 · see citing works
Stojanovic, S., Knowlton, C. J., Egger-Mackrodt, R., Mankel, J., Shin, J., Lammel, S., Canavier, C. C., & Roeper, J. (2025) · Journal of Neuroscience · doi:10.1523/jneurosci.0361-25.2025 · Cited by 6 · see citing works
Hadjas, L. C., Kollman, G. J., Linderhof, L., Xia, M., Mansur, S., Saint‐Pierre, M., Lim, B. K., Lee, E. B., Cicchetti, F., Awatramani, R. B., et al. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.06.03.657460 · Cited by 6 · see citing works
Karaman, G. D., & Selçuk, S. A. (2021) · DergiPark (Istanbul University) · Cited by 5 · see citing works
Dopaminergic Prediction Errors Persevere in the Nucleus Accumbens Core during Negative Reinforcement
Hollon, N. G., Soden, M. E., & Wanat, M. J. (2013) · Journal of Neuroscience · doi:10.1523/jneurosci.5762-12.2013 · Cited by 5 · see citing works
Anterior cingulate cortex monitors action state and action content in complex associative learningPreprint
Huang, W., Hall, A. F., Kawalec, N., Opalka, A. N., Liu, J., & Wang, D. V. (2025) · eLife · doi:10.7554/elife.105774 · Cited by 5 · see citing works
Self-citationLaLumiere, R. T. (2014) · Elsevier eBooks · doi:10.1016/b978-0-12-408139-0.00005-5 · Cited by 4 · see citing works
Piri, M., Nasehi, M., Mafi, F., Shahin, M.-S., & Zarrindast, M. R. (2012) · The Journal of Qazvin University of Medical Sciences · Cited by 4 · see citing works
The Influence of Personality Trait on Effective Leadership: The Role of Dopamine
Kurtulmuş, B. E., Katrinli, Ş., & Katrinli, A. E. (2019) · Dokuz Eylül Üniversitesi İşletme Fakültesi Dergisi · doi:10.24889/ifede.433230 · Cited by 4 · see citing works
Tsien, J. Z., Li, M., Osan, R. M., Chen, G., Lin, L., Wang, P. L., Frey, S., Frey, J. U., Zhu, D., Liu, T., et al. (2013) · Science China Life Sciences · doi:10.1007/s11427-013-4521-1 · Cited by 4 · see citing works
Self-citationLimbrick‐Oldfield, E. H., Leech, R., Wise, R. G., & Ungless, M. A. (2018) · European Journal of Neuroscience · doi:10.1111/ejn.14288 · Cited by 4 · see citing works
Neural circuits mediating aversive olfactory conditioning in Drosophila
Galili, D. S. (2014) · Elektronische Hochschulschriften der LMU München (Ludwig-Maximilians-Universität München) · doi:10.5282/edoc.17542 · Cited by 3 · see citing works
Rogers, A. D., Castro, E. M., Lotfipour, S., & Leslie, F. M. (2025) · Neuropharmacology · doi:10.1016/j.neuropharm.2025.110350 · Cited by 2 · see citing works
Cultivating Calm: Applications of Biophilic Design for Reducing ICU Nurse Burnout and Stress
Bazaid, R. H., Hamilton, E. M., & Parkinson, S. F. (2025) · Journal of Interior Design · doi:10.1177/10717641251381800 · Cited by 2 · see citing works
Ivlieva, N. Y., Timofeeva, N. O., & Ivliev, D. A. (2014) · The Journal of Cognitive Science · Cited by 2 · see citing works
STUDY OF BIOPHILIC CONCEPT IN PONDOK INDAH BINTARO HOSPITAL
Rahman, I. F., & Lissimia, F. (2024) · BORDER · doi:10.33005/border.v4i1.91 · Cited by 1 · see citing works
Broccoli, L., Bernardi, R. E., Giannone, F., Hoppe, A., Jüngling, K., Borroto‐Escuela, D. O., Rimondini, R., de la Mora, M. P., Halbach, O. V. B. U., Fuxé, K., et al. (2025) · Frontiers in Pharmacology · doi:10.3389/fphar.2025.1677510 · Cited by 1 · see citing works
Multidimensional decision making
Mills‐Finnerty, C. (2015) · doi:10.7282/t3b27x9r · Cited by 1 · see citing works
Drug-induced synaptic plasticity in addiction : the mesolimbic dopamine pathway and benzodiazepines
Panhelainen, A. E. (2012) · Työväentutkimus Vuosikirja
Structural plasticity of the mesolimbic system associated with female sexual reward.
Michael, N. A. (2012) · University of Minnesota Digital Conservancy (University of Minnesota)
- Authors
- Wang, D. V., & Tsien, J. Z.
- Affiliations
- East China Normal University (CN)
- Corresponding author
- Tsien, Joe Z.
- ORCID
- Wang, Dong V.
- Venue
- PLoS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2011-02-15
- Volume
- 6
- Issue
- 2
- Pages
- e17047
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC3039659
- OpenAlex
- W2083000736
- Cited by
- 116
- References
- 53
- Citations by year
- 2026: 2 · 2025: 8 · 2024: 5 · 2023: 1 · 2022: 4 · 2021: 4 · 2020: 6 · 2019: 6 · 2018: 6 · 2017: 5 · 2016: 8 · 2015: 7 · 2014: 17 · 2013: 13 · 2012: 17
- FWCI
- 7.15
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- PLoS ONE (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Figshare (submittedVersion, cc-by)
- Funders
- Georgia Research Alliance
- National Institute on Aging (AG025918, R01AG034663, AG024022, R01AG025918, AG034663, R01AG024022)
- National Institute of Mental Health (MH060236, R01MH060236)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
- Keywords
- ventral tegmental area, dopaminergic neurons, fear, reward, contextual modulation, free fall, mice
- MeSH terms
- Animals, Fear, Male, Mice, Inbred C57BL, Motivation, Time Factors, Ventral Tegmental Area, Mice, Dopaminergic Neurons
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.
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