Afferent modulation of dopamine neuron firing differentially regulates tonic and phasic dopamine transmission
Abstract
The mesolimbic dopamine system is centrally involved in reward and goal-directed behavior, and it has been implicated in multiple psychiatric disorders. Understanding the mechanism by which dopamine participates in these activities requires comprehension of the dynamics of dopamine release. Here we report dissociable regulation of dopamine neuron discharge by two separate afferent systems in rats; inhibition of pallidal afferents selectively increased the population activity of dopamine neurons, whereas activation of pedunculopontine inputs increased burst firing. Only the increase in population activity increased ventral striatal dopamine efflux. After blockade of dopamine reuptake, however, enhanced bursting increased dopamine efflux three times more than did enhanced population activity. These results provide insight into multiple regulatory systems that modulate dopamine system function: burst firing induces massive synaptic dopamine release, which is rapidly removed by reuptake before escaping the synaptic cleft, whereas increased population activity modulates tonic extrasynaptic dopamine levels that are less influenced by reuptake.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
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?
Burst firing in dopaminergic neurons is potently driven by the brainstem pedunculopontine tegmentum, which provides a glutamatergic input acting via NMDARs.
“Burst firing in dopaminergic neurons is potently driven by the brainstem pedunculopontine tegmentum (PPTg), which provides a glutamatergic input that acts via NMDARs ([39, 40] see Box 3).”
From A neoHebbian framework for episodic memory; role of dopamine-dependent late LTP (2011) · cites this paper as [39]
The PPTg regulates burst firing of dopamine cells rather than their tonic resting activity.
“The PPTg regulates burst firing of dopamine cells rather than their tonic resting activity [[39]].”
From A neoHebbian framework for episodic memory; role of dopamine-dependent late LTP (2011) · cites this paper as [39]
Cites
Predictive reward signal of dopamine neurons
Schultz, W. (1998) · Journal of Neurophysiology · doi:10.1152/jn.1998.80.1.1 · Cited by 4,564 · see citing works
Voltage-dependent block by Mg2+ of NMDA responses in spinal cord neurones
Mayer, M. L., Westbrook, G. L., & Guthrie, P. B. (1984) · Nature · doi:10.1038/309261a0 · Cited by 2,906 · see citing works
A review of MRI findings in schizophrenia
Shenton, M. E., Dickey, C. C., Frumin, M., & McCarley, R. W. (2001) · Schizophrenia Research · doi:10.1016/s0920-9964(01)00163-3 · Cited by 2,346 · see citing works
Grace, A. A. (1991) · Neuroscience · doi:10.1016/0306-4522(91)90196-u · Cited by 1,831 · see citing works
Self-citationGrace, A. A., & Bunney, B. S. (1983) · Neuroscience · doi:10.1016/0306-4522(83)90135-5 · Cited by 937 · see citing works
Self-citationGonon, F. G. (1988) · Neuroscience · doi:10.1016/0306-4522(88)90307-7 · Cited by 676 · see citing works
Floresco, S., Todd, C. L., & Grace, A. A. (2001) · Journal of Neuroscience · doi:10.1523/jneurosci.21-13-04915.2001 · Cited by 556 · see citing works
Self-citationIs the short-latency dopamine response too short to signal reward error?
Redgrave, P., Prescott, T. J., & Gurney, K. (1999) · Trends in Neurosciences · doi:10.1016/s0166-2236(98)01373-3 · Cited by 506 · see citing works
Efflux of dopamine from the synaptic cleft in the nucleus accumbens of the rat brain
Garris, P. A., Ciolkowski, E. L., Pastore, P., & Wightman, R. M. (1994) · Journal of Neuroscience · doi:10.1523/jneurosci.14-10-06084.1994 · Cited by 475 · see citing works
Richfield, E. K., Penney, J. B., & Young, A. B. (1989) · Neuroscience · doi:10.1016/0306-4522(89)90168-1 · Cited by 448 · see citing works
Two transpallidal pathways originating in the rat nucleus accumbens
Zahm, D. S., & Heimer, L. (1990) · The Journal of Comparative Neurology · doi:10.1002/cne.903020302 · Cited by 406 · see citing works
Oakman, S., Faris, P. L., Kerr, P., Cozzari, C., & Hartman, B. (1995) · Journal of Neuroscience · doi:10.1523/jneurosci.15-09-05859.1995 · Cited by 384 · see citing works
Laruelle, M. (2000) · Brain research. Brain research reviews · doi:10.1016/s0165-0173(99)00054-5 · Cited by 347 · see citing works
Wickens, J. R., Begg, A., & Arbuthnott, G. W. (1996) · Neuroscience · doi:10.1016/0306-4522(95)00436-m · Cited by 294 · see citing works
Transient changes in mesolimbic dopamine and their association with ‘reward’
Wightman, R. M., & Robinson, D. L. (2002) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.2002.01005.x · Cited by 280 · see citing works
Floresco, S., Blaha, C. D., Yang, C. R., & Phillips, A. G. (2001) · Journal of Neuroscience · doi:10.1523/jneurosci.21-08-02851.2001 · Cited by 242 · see citing works
Self-citationNirenberg, M. J., Chan, J., Pohorille, A., Vaughan, R. A., Uhl, G. R., Kuhar, M. J., & Pickel, V. M. (1997) · Journal of Neuroscience · doi:10.1523/jneurosci.17-18-06899.1997 · Cited by 242 · see citing works
Afferent modulation of dopamine neuron firing patterns
Kitai, S. T., Shepard, P. D., Callaway, J. C., & Scroggs, R. S. (1999) · Current Opinion in Neurobiology · doi:10.1016/s0959-4388(99)00040-9 · Cited by 234 · see citing works
Meiergerd, S. M., Patterson, T. A., & Schenk, J. O. (1993) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.1993.tb02185.x · Cited by 225 · see citing works
Clements, J. R., & Grant, S. (1990) · Neuroscience Letters · doi:10.1016/0304-3940(90)90170-e · Cited by 203 · see citing works
Cortical regulation of subcortical dopamine systems and its possible relevance to schizophrenia
Grace, A. A. (1993) · Journal of Neural Transmission · doi:10.1007/bf01245228 · Cited by 185 · see citing works
Self-citationTonic D2-mediated attenuation of cortical excitation in nucleus accumbens neurons recorded in vitro
O’Donnell, P., & Grace, A. A. (1994) · Brain Research · doi:10.1016/0006-8993(94)90263-1 · Cited by 169 · see citing works
Self-citationYang, C., & Mogenson, G. J. (1987) · Neuroscience · doi:10.1016/0306-4522(87)90179-5 · Cited by 168 · see citing works
Howland, J. G., Taepavarapruk, P., & Phillips, A. G. (2002) · Journal of Neuroscience · doi:10.1523/jneurosci.22-03-01137.2002 · Cited by 155 · see citing works
Milner, K. L., & Mogenson, G. J. (1988) · Brain Research · doi:10.1016/0006-8993(88)90031-5 · Cited by 129 · see citing works
Karreman, M., Westerink, B. H. C., & Moghaddam, B. (1996) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.1996.67020601.x · Cited by 128 · see citing works
Phillips, A. G., Atkinson, L. J., Blackburn, J. R., & Blaha, C. D. (1993) · Canadian Journal of Physiology and Pharmacology · doi:10.1139/y93-059 · Cited by 113 · see citing works
Gronier, B., & Rasmussen, K. (1998) · British Journal of Pharmacology · doi:10.1038/sj.bjp.0701850 · Cited by 107 · see citing works
Striatal Nitric Oxide Signaling Regulates the Neuronal Activity of Midbrain Dopamine Neurons In Vivo
West, A. R., & Grace, A. A. (2000) · Journal of Neurophysiology · doi:10.1152/jn.2000.83.4.1796 · Cited by 103 · see citing works
Self-citationWest, A. R., & Galloway, M. P. (1997) · Neuropharmacology · doi:10.1016/s0028-3908(97)00148-2 · Cited by 102 · see citing works
Self-citationConditioned appetitive stimulus increases extracellular dopamine in the nucleus accumbens of the rat
Datla, K. P., Ahier, R. G., Young, A. M. J., Gray, J. A., & Joseph, M. H. (2002) · European Journal of Neuroscience · doi:10.1046/j.1460-9568.2002.02249.x · Cited by 75 · see citing works
Maslowski, R. J., & Napier, T. C. (1994) · Neuroscience · doi:10.1016/0306-4522(94)90347-6 · Cited by 66 · see citing works
Moore, H. M., Todd, C. L., & Grace, A. A. (1998) · Journal of Neuroscience · doi:10.1523/jneurosci.18-13-05068.1998 · Cited by 46 · see citing works
Self-citationKitamura, M., Ikeda, H., Koshikawa, N., & Cools, A. R. (2001) · Neuroscience · doi:10.1016/s0306-4522(01)00053-7 · Cited by 33 · see citing works
Wu, M., Hrycyshyn, A. W., & Brudzyński, S. M. (1996) · Brain Research · doi:10.1016/s0006-8993(96)00859-1 · Cited by 30 · see citing works
Tsai, C. T., Mogenson, G. J., Wu, M., & Yang, C. (1989) · Brain Research · doi:10.1016/0006-8993(89)90139-x · Cited by 25 · see citing works
Injected muscimol in pedunculopontine tegmental nucleus alters ethanol self-administration
Samson, H. H., & Chappell, A. M. (2001) · Alcohol · doi:10.1016/s0741-8329(00)00122-1 · Cited by 25 · see citing works
Effects of Lesions in the Medial Prefrontal Cortex on the Activity of Midbrain Dopamine Neurons
Seong, S. (1996) · Neuropsychopharmacology · doi:10.1016/s0893-133x(96)00052-8 · Cited by 24 · see citing works
Synaptology of Dopamine Neurons
Sesack, S. R. (2002) · Handbook of experimental pharmacology · doi:10.1007/978-3-642-56051-4_4 · Cited by 18 · see citing works
Disappearance of particulate tectal protein during optic nerve degeneration in the pigeon
Cuénod, M., Markó, P., & Niederer, E. M. (1973) · Brain Research · doi:10.1016/0006-8993(73)90434-4 · Cited by 16 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
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
Self-citationThe principal features and mechanisms of dopamine modulation in the prefrontal cortex
Seamans, J. K., & Yang, C. R. (2004) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2004.05.006 · Cited by 1,592 · see citing works
Reconsidering anhedonia in depression: Lessons from translational neuroscience
Treadway, M. T., & Zald, D. H. (2011) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2010.06.006 · Cited by 1,579 · see citing works
The mysterious motivational functions of mesolimbic dopamine
Salamone, J. D., & Correa, M. (2012) · Neuron · doi:10.1016/j.neuron.2012.10.021 · Cited by 1,418 · 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
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
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
Self-citationTonic dopamine: Opportunity costs and the control of response vigor
Niv, Y., Daw, N. D., Joel, D., & Dayan, P. (2007) · Psychopharmacology · doi:10.1007/s00213-006-0502-4 · Cited by 1,133 · 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: Functions, Signaling, and Association with Neurological Diseases
Klein, M. O., Battagello, D. S., Cardoso, A. R., Hauser, D. N., Bittencourt, J. C., & Correa, R. G. (2019) · Cellular and Molecular Neurobiology · doi:10.1007/s10571-018-0632-3 · Cited by 1,073 · see citing works
Regulation of firing of dopaminergic neurons and control of goal-directed behaviors
Grace, A. A., Floresco, S. B., Goto, Y., & Lodge, D. J. (2007) · Trends in Neurosciences · doi:10.1016/j.tins.2007.03.003 · Cited by 1,034 · see citing works
Self-citationCortico-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
Self-citationUnique 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
The dopamine motive system: implications for drug and food addiction
Volkow, N. D., Wise, R. A., & Baler, R. (2017) · Nature Reviews Neuroscience · doi:10.1038/nrn.2017.130 · Cited by 939 · see citing works
The 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
Self-citationThe scientific and clinical basis for the treatment of Parkinson disease (2009)
Olanow, C. W., Stern, M. B., & Sethi, K. D. (2009) · Neurology · doi:10.1212/wnl.0b013e3181a1d44c · Cited by 918 · see citing works
Berke, J. D. (2018) · Nature Neuroscience · doi:10.1038/s41593-018-0152-y · Cited by 904 · see citing works
Cools, R. (2006) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2005.03.024 · Cited by 903 · see citing works
The Neuroscience of Drug Reward and Addiction
Volkow, N. D., Michaelides, M., & Baler, R. (2019) · Physiological Reviews · doi:10.1152/physrev.00014.2018 · Cited by 863 · see citing works
A common neurobiology for pain and pleasure
Leknes, S., & Tracey, I. (2008) · Nature Reviews Neuroscience · doi:10.1038/nrn2333 · Cited by 784 · see citing works
Uniform Inhibition of Dopamine Neurons in the Ventral Tegmental Area by Aversive Stimuli
Ungless, M. A., Magill, P. J., & Bolam, J. P. (2004) · Science · doi:10.1126/science.1093360 · Cited by 782 · see citing works
Bilder, R. M., Volavka, J., Lachman, H. M., & Grace, A. A. (2004) · Neuropsychopharmacology · doi:10.1038/sj.npp.1300542 · Cited by 769 · see citing works
Self-citationDopamine system dysregulation in major depressive disorders
Belujon, P., & Grace, A. A. (2017) · International Journal of Neuropsychopharmacology · doi:10.1093/ijnp/pyx056 · Cited by 754 · see citing works
Self-citationReinforcement learning in the brain
Niv, Y. (2009) · Journal of Mathematical Psychology · doi:10.1016/j.jmp.2008.12.005 · Cited by 724 · see citing works
Dissociable dopamine dynamics for learning and motivation
Mohebi, A., Pettibone, J. R., Hamid, A., Wong, J.-M. T., Vinson, L. T., Patriarchi, T., Tian, L., Kennedy, R. T., & Berke, J. D. (2019) · Nature · doi:10.1038/s41586-019-1235-y · Cited by 714 · see citing works
Daphna Shohamy, A., & Adcock, R. A. (2010) · Trends in Cognitive Sciences · doi:10.1016/j.tics.2010.08.002 · Cited by 702 · see citing works
Alcaro, A., Huber, R., & Panksepp, J. (2007) · Brain Research Reviews · doi:10.1016/j.brainresrev.2007.07.014 · Cited by 614 · see citing works
Dopaminergic modulation of limbic and cortical drive of nucleus accumbens in goal-directed behavior
Goto, Y., & Grace, A. A. (2005) · Nature Neuroscience · doi:10.1038/nn1471 · Cited by 576 · see citing works
Self-citationOlanow, C. W., Obeso, J. A., & Stocchi, F. (2006) · The Lancet Neurology · doi:10.1016/s1474-4422(06)70521-x · Cited by 549 · see citing works
Ventral pallidum roles in reward and motivation
Smith, K. S., Tindell, A. J., Aldridge, J. W., & Berridge, K. C. (2009) · Behavioural Brain Research · doi:10.1016/j.bbr.2008.09.038 · Cited by 548 · see citing works
Glutamatergic Afferents of the Ventral Tegmental Area in the Rat
Geisler, S., Derst, C., Veh, R. W., & Zahm, D. S. (2007) · Journal of Neuroscience · doi:10.1523/jneurosci.0012-07.2007 · Cited by 486 · see citing works
Mapping anhedonia onto reinforcement learning: a behavioural meta-analysis
Huys, Q. J., Pizzagalli, D. A., Bogdan, R., & Dayan, P. (2013) · Biology of Mood & Anxiety Disorders · doi:10.1186/2045-5380-3-12 · Cited by 480 · see citing works
Wang, H., & Morales, M. (2009) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2008.06576.x · Cited by 478 · 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
Self-citationSerotonin and dopamine: unifying affective, activational, and decision functions.
Cools, R., Nakamura, K., & Daw, N. D. (2011) · Neuropsychopharmacology · doi:10.1038/npp.2010.121 · Cited by 464 · see citing works
Opponency revisited: competition and cooperation between dopamine and serotonin
Boureau, Y.-L., & Dayan, P. (2011) · Neuropsychopharmacology · doi:10.1038/npp.2010.151 · Cited by 456 · see citing works
Nicotine addiction and nicotinic receptors: lessons from genetically modified mice
Changeux, J.-P. (2010) · Nature Reviews Neuroscience · doi:10.1038/nrn2849 · Cited by 453 · see citing works
Lodge, D., & Grace, A. (2007) · Journal of Neuroscience · doi:10.1523/jneurosci.2847-07.2007 · Cited by 475 · see citing works
Self-citationStress and the dopaminergic reward system
Baik, J. (2020) · Experimental & Molecular Medicine · doi:10.1038/s12276-020-00532-4 · Cited by 446 · 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
Self-citationZweifel, L. S., Parker, J. G., Lobb, C. J., Rainwater, A., Wall, V. Z., Fadok, J. P., Darvas, M., Kim, M. J., Mizumori, S. J. Y., Paladini, C. A., et al. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0813415106 · Cited by 426 · see citing works
Influence of Phasic and Tonic Dopamine Release on Receptor Activation
Dreyer, J. K., Herrik, K. F., Berg, R. W., & Hounsgaard, J. (2010) · Journal of Neuroscience · doi:10.1523/jneurosci.1894-10.2010 · Cited by 418 · see citing works
Wise, R. A., & Robble, M. A. (2020) · Annual Review of Psychology · doi:10.1146/annurev-psych-010418-103337 · Cited by 418 · see citing works
The ventral basal ganglia, a selection mechanism at the crossroads of space, strategy, and reward.
Humphries, M. D., & Prescott, T. J. (2009) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2009.11.003 · Cited by 414 · see citing works
Oakman, S., Faris, P. L., Kerr, P., Cozzari, C., & Hartman, B. (1995) · Journal of Neuroscience · doi:10.1523/jneurosci.15-09-05859.1995 · Cited by 384 · see citing works
Afferents of the ventral tegmental area in the rat-anatomical substratum for integrative functions
Geisler, S., & Zahm, D. S. (2005) · The Journal of Comparative Neurology · doi:10.1002/cne.20668 · Cited by 379 · see citing works
DAncing past the DAT at a DA synapse
Cragg, S. J., & Rice, M. E. (2004) · Trends in Neurosciences · doi:10.1016/j.tins.2004.03.011 · Cited by 373 · see citing works
Oxytocin, motivation and the role of dopamine
Love, T. M. (2014) · Pharmacology Biochemistry and Behavior · doi:10.1016/j.pbb.2013.06.011 · Cited by 369 · 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
“This influence of the PPT/LDT arises, at least in part, because these areas contribute to the phasic burst firing of DA neurons (Floresco et al. 2003, Lodge & Grace 2006).”
BackgroundModel-based and model-free Pavlovian reward learning: Revaluation, revision, and revelation
Dayan, P., & Berridge, K. C. (2014) · Cognitive, Affective, & Behavioral Neuroscience · doi:10.3758/s13415-014-0277-8 · Cited by 357 · see citing works
Hippocampal dysregulation of dopamine system function and the pathophysiology of schizophrenia
Lodge, D. J., & Grace, A. A. (2011) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2011.05.001 · Cited by 349 · see citing works
Self-citationThe laterodorsal tegmentum is essential for burst firing of ventral tegmental area dopamine neurons
Lodge, D. J., & Grace, A. A. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0510715103 · Cited by 349 · see citing works
Self-citationPissadaki, E. K., & Bolam, J. P. (2013) · Frontiers in Computational Neuroscience · doi:10.3389/fncom.2013.00013 · Cited by 349 · see citing works
Designer receptors show role for ventral pallidum input to ventral tegmental area in cocaine seeking
Mahler, S. V., Vazey, E. M., Beckley, J. T., Keistler, C., McGlinchey, E. M., Kaufling, J., Wilson, S. P., Deisseroth, K. A., Woodward, J. J., & Aston‐Jones, G. (2014) · Nature Neuroscience · doi:10.1038/nn.3664 · Cited by 343 · see citing works
The Yin and Yang of dopamine release: a new perspective
GOTO, Y., OTANI, S., & GRACE, A. (2007) · Neuropharmacology · doi:10.1016/j.neuropharm.2007.07.007 · Cited by 342 · see citing works
Self-citationThe 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
Rice, M. E., & Cragg, S. J. (2008) · Brain Research Reviews · doi:10.1016/j.brainresrev.2008.02.004 · Cited by 340 · see citing works
The mesoaccumbens dopamine in coping with stress
Cabib, S., & Puglisi-Allegra, S. (2012) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2011.04.012 · Cited by 329 · see citing works
Gliotransmission: Beyond Black-and-White
Savtchouk, I., & Volterra, A. (2018) · The Journal of Neuroscience · doi:10.1523/jneurosci.0017-17.2017 · Cited by 325 · see citing works
Increased Occupancy of Dopamine Receptors in Human Striatum during Cue-Elicited Cocaine Craving
Wong, D. F., Kuwabara, H., Schretlen, D. J., Bonson, K. R., Zhou, Y., Nandi, A., Brašić, J. R., Kimes, A. S., Maris, M. A., Kumar, A., et al. (2006) · Neuropsychopharmacology · doi:10.1038/sj.npp.1301194 · Cited by 311 · see citing works
Self-citationSpatial and temporal scales of dopamine transmission
Liu, C., Goel, P., & Kaeser, P. S. (2021) · Nature reviews. Neuroscience · doi:10.1038/s41583-021-00455-7 · Cited by 302 · see citing works
The role of mesolimbic dopamine in the development and maintenance of ethanol reinforcement
Gonzales, R. A., Job, M. O., & Doyon, W. M. (2004) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2004.06.002 · Cited by 297 · see citing works
Hierarchical Control of Dopamine Neuron-Firing Patterns by Nicotinic Receptors
Mameli-Engvall, M., Evrard, A., Pons, S., Maskos, U., Svensson, T. H., Changeux, J.-P., & Faure, P. (2006) · Neuron · doi:10.1016/j.neuron.2006.05.007 · Cited by 296 · see citing works
Dahan, L., Astier, B., Vautrelle, N., Urbain, N., Kocsis, B., & Chouvet, G. (2006) · Neuropsychopharmacology · doi:10.1038/sj.npp.1301251 · Cited by 289 · see citing works
Relation of obesity to consummatory and anticipatory food reward
Stice, E. M., Spoor, S. T. P., Ng, J., & Zald, D. H. (2009) · Physiology & Behavior · doi:10.1016/j.physbeh.2009.03.020 · Cited by 289 · see citing works
Díaz-Mataix, L., Scorza, M. C., Bortolozzi, A. A., Tóth, M., Celada, P., & Artigas, F. (2005) · Journal of Neuroscience · doi:10.1523/jneurosci.2999-05.2005 · Cited by 288 · see citing works
Matt, S. M., & Gaskill, P. J. (2019) · Journal of Neuroimmune Pharmacology · doi:10.1007/s11481-019-09851-4 · Cited by 286 · see citing works
Understanding wiring and volume transmission
Agnati, L. F., Guidolin, D., Guescini, M., Genedani, S., & Fuxé, K. (2010) · Brain Research Reviews · doi:10.1016/j.brainresrev.2010.03.003 · Cited by 283 · see citing works
Dopamine 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
Venton, B. J., Zhang, H., Garris, P. A., Phillips, P. E. M., Sulzer, D., & Wightman, R. M. (2003) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.2003.02109.x · Cited by 281 · see citing works
Lodge, D. J., & Grace, A. A. (2006) · Neuropsychopharmacology · doi:10.1038/sj.npp.1300963 · Cited by 280 · see citing works
Self-citationSerotonin, inhibition, and negative mood
Dayan, P., & Huys, Q. J. M. (2008) · PLoS Computational Biology · doi:10.1371/journal.pcbi.0040004 · Cited by 263 · see citing works
Acetylcholine–Dopamine Interactions in the Pathophysiology and Treatment of CNS Disorders
Lester, D. B., Rogers, T. D., & Blaha, C. D. (2010) · CNS Neuroscience & Therapeutics · doi:10.1111/j.1755-5949.2010.00142.x · Cited by 260 · 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
Nucleus accumbens medium spiny neurons subtypes signal both reward and aversion
Soares-Cunha, C., de Vasconcelos, N. A. P., Coimbra, B., Domingues, A. V., Silva, J. M., Loureiro-Campos, E., Gaspar, R., Sotiropoulos, I., Sousa, N., & Rodrigues, A. J. (2020) · Molecular Psychiatry · doi:10.1038/s41380-019-0484-3 · Cited by 256 · see citing works
What is reinforced by phasic dopamine signals?
Redgrave, P., GURNEY, K. N., & Reynolds, J. N. J. (2007) · Brain Research Reviews · doi:10.1016/j.brainresrev.2007.10.007 · Cited by 254 · see citing works
Düzel, E., Bunzeck, N., Guitart-Masip, M., & Düzel, S. (2010) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2009.08.006 · Cited by 249 · see citing works
Rethinking the Pedunculopontine Nucleus: From Cellular Organization to Function
Mena‐Segovia, J., & Bolam, J. P. (2017) · Neuron · doi:10.1016/j.neuron.2017.02.027 · Cited by 249 · see citing works
Dopamine Secretion Is Mediated by Sparse Active Zone-like Release Sites
Liu, C., Kershberg, L., Wang, J., Schneeberger, S., & Kaeser, P. S. (2018) · Cell · doi:10.1016/j.cell.2018.01.008 · Cited by 249 · see citing works
Increased phasic dopamine signaling in the mesolimbic pathway during social defeat in rats
Anstrom, K. K., Miczek, K. A., & Budygin, E. A. (2009) · Neuroscience · doi:10.1016/j.neuroscience.2009.03.023 · Cited by 246 · see citing works
Gene–gene interaction associated with neural reward sensitivity
Yacubian, J., Sommer, T., Schroeder, K., Gläscher, J., Kalisch, R., Leuenberger, B., Braus, D. F., & Büchel, C. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0702029104 · Cited by 241 · 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
Alcaro, A., & Panksepp, J. (2011) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2011.03.002 · Cited by 240 · see citing works
Amygdala-Ventral Pallidum Pathway Decreases Dopamine Activity After Chronic Mild Stress in Rats
Chang, C.-H., & Grace, A. A. (2014) · Biological Psychiatry · doi:10.1016/j.biopsych.2013.09.020 · Cited by 239 · see citing works
Self-citationThe roles of the reward system in sleep and dreaming
Perogamvros, L., & Schwartz, S. (2012) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2012.05.010 · Cited by 239 · see citing works
GABAergic control of substantia nigra dopaminergic neurons
Tepper, J. M., & Lee, C. R. (2007) · Progress in brain research · doi:10.1016/s0079-6123(06)60011-3 · Cited by 235 · see citing works
Sombers, L. A., Beyene, M., Carelli, R. M., & Wightman, R. M. (2009) · Journal of Neuroscience · doi:10.1523/jneurosci.5562-08.2009 · Cited by 231 · see citing works
Krugel, L. K., Biele, G., Mohr, P. N. C., Li, S.-C., & Heekeren, H. R. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0905191106 · Cited by 229 · see citing works
Riegel, A. C., & Lupica, C. R. (2004) · Journal of Neuroscience · doi:10.1523/jneurosci.3695-04.2004 · Cited by 227 · 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
Aragona, B. J., Cleaveland, N. A., Stuber, G. D., Day, J. J., Carelli, R. M., & Wightman, R. M. (2008) · Journal of Neuroscience · doi:10.1523/jneurosci.2225-08.2008 · Cited by 225 · see citing works
Grace, A. A. (2011) · Neuropharmacology · doi:10.1016/j.neuropharm.2011.05.011 · Cited by 225 · see citing works
Self-citationThe activation of 5‐HT2A receptors in prefrontal cortex enhances dopaminergic activity
Bortolozzi, A. A., Díaz-Mataix, L., Scorza, M. C., Celada, P., & Artigas, F. (2005) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2005.03485.x · Cited by 224 · see citing works
Besser, M. J., Ganor, Y., & Levite, M. (2005) · Journal of Neuroimmunology · doi:10.1016/j.jneuroim.2005.07.013 · Cited by 222 · see citing works
Stuber, G. D., Roitman, M. F., Phillips, P. E. M., Carelli, R. M., & Wightman, R. M. (2005) · Neuropsychopharmacology · doi:10.1038/sj.npp.1300619 · Cited by 217 · see citing works
Functional imaging of the human dopaminergic midbrain
Düzel, E., Bunzeck, N., Guitart-Masip, M., Wittmann, B., Schott, B. H., & Tobler, P. N. (2009) · Trends in Neurosciences · doi:10.1016/j.tins.2009.02.005 · Cited by 216 · see citing works
Dopamine Modulates Reward-Related Vigor
Beierholm, U., Guitart‐Masip, M., Economides, M., Chowdhury, R., Düzel, E., Dolan, R. J., & Dayan, P. (2013) · Neuropsychopharmacology · doi:10.1038/npp.2013.48 · Cited by 216 · see citing works
Lodge, D. J., & Grace, A. A. (2009) · Behavioural Brain Research · doi:10.1016/j.bbr.2009.01.031 · Cited by 215 · see citing works
Self-citationChronic stress triggers social aversion via glucocorticoid receptor in dopaminoceptive neurons
Barik, J., Marti, F., Morel, C., Fernandez, S. P., Lanteri, C., Godeheu, G., Tassin, J.-P., Mombereau, C., Faure, P., & Tronche, F. (2013) · Science · doi:10.1126/science.1226767 · Cited by 214 · see citing works
- Authors
- Floresco, S. B., West, A. R., Ash, B., Moore, H., & Grace, A. A.
- Affiliations
- University of Pittsburgh (US)
- Corresponding author
- Floresco, Stan B
- Grace, Anthony A
- Venue
- Nature Neuroscience
- Published
- 2003-08-03
- Volume
- 6
- Issue
- 9
- Pages
- 968-973
- ISSN
- 1097-6256 (ISSN-L)
- 1546-1726
- OpenAlex
- W1994984635
- Cited by
- 1,106
- References
- 40
- Citations by year
- 2026: 23 · 2025: 33 · 2024: 37 · 2023: 33 · 2022: 49 · 2021: 43 · 2020: 46 · 2019: 50 · 2018: 67 · 2017: 44 · 2016: 61 · 2015: 54 · 2014: 73 · 2013: 55 · 2012: 60
- FWCI
- 13.17
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Institute of Mental Health (F32MH011305)
- 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 › Neural and Behavioral Psychology Studies
- Keywords
- dopaminergic neurons, mesolimbic dopamine system, pedunculopontine nucleus, burst firing, tonic dopamine release, dopamine reuptake, ventral striatum, dopamine efflux, population activity, reward
- MeSH terms
- Afferent Pathways, Animals, Dopamine, Male, Mesencephalon, Synaptic Transmission, Neurons, Nucleus Accumbens, Rats, Sprague-Dawley, Ventral Tegmental Area, GABA Antagonists, Rats
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
