1932

Abstract

To benefit from opportunities and cope with challenges in the environment, animals must adapt their behavior to acquire rewards and to avoid punishments. Maladaptive changes in the neuromodulatory systems and neural circuits for reward and aversion can lead to manifestation of several prominent psychiatric disorders including addiction and depression. Recent progress is pushing the boundaries of knowledge on two major fronts in research on reward and aversion: First, new layers of complexity have been reported on the functions of dopamine (DA) and serotonin (5-HT) neuromodulatory systems in reward and aversion. Second, specific circuit components in the neural pathways that encode reward and aversion have begun to be identified. This review aims to outline historic perspectives and new insights into the functions of DA and 5-HT systems in coding the distinct components of rewards. It also highlights recent advances in neural circuit studies enabled by new technologies, such as cell-type-specific electrophysiology and tracing, and optogenetics-based behavioral manipulation. This knowledge may provide guidance for developing novel treatment strategies for neuropsychiatric diseases related to the malfunction of the reward system.

Keyword(s): aversiondopamineNAcrewardserotoninVTA
Loading

Article metrics loading...

/content/journals/10.1146/annurev-neuro-070815-014106
2016-07-08
2024-03-28
Loading full text...

Full text loading...

/deliver/fulltext/neuro/39/1/annurev-neuro-070815-014106.html?itemId=/content/journals/10.1146/annurev-neuro-070815-014106&mimeType=html&fmt=ahah

Literature Cited

  1. Abercrombie ED, Keefe KA, DiFrischia DS, Zigmond MJ. 1989. Differential effect of stress on in vivo dopamine release in striatum, nucleus accumbens, and medial frontal cortex. J. Neurochem. 52:1655–58 [Google Scholar]
  2. Adamantidis AR, Tsai HC, Boutrel B, Zhang F, Stuber GD. et al. 2011. Optogenetic interrogation of dopaminergic modulation of the multiple phases of reward-seeking behavior. J. Neurosci. 31:10829–35 [Google Scholar]
  3. Akerboom J, Chen TW, Wardill TJ, Tian L, Marvin JS. et al. 2012. Optimization of a GCaMP calcium indicator for neural activity imaging. J. Neurosci. 32:13819–40 [Google Scholar]
  4. Al-Hasani R, McCall JG, Shin G, Gomez AM, Schmitz GP. et al. 2015. Distinct subpopulations of nucleus accumbens dynorphin neurons drive aversion and reward. Neuron 87:1063–77 [Google Scholar]
  5. Amo R, Fredes F, Kinoshita M, Aoki R, Aizawa H. et al. 2014. The habenulo-raphe serotonergic circuit encodes an aversive expectation value essential for adaptive active avoidance of danger. Neuron 84:1034–48 [Google Scholar]
  6. Beier KT, Steinberg EE, DeLoach KE, Xie S, Miyamichi K. et al. 2015. Circuit architecture of VTA dopamine neurons revealed by systematic input-output mapping. Cell 162:622–34 [Google Scholar]
  7. Berridge KC, Kringelbach ML. 2015. Pleasure systems in the brain. Neuron 86:646–64 [Google Scholar]
  8. Berridge KC, Robinson TE. 1998. What is the role of dopamine in reward: hedonic impact, reward learning, or incentive salience?. Brain Res. Brain Res. Rev. 28:309–69 [Google Scholar]
  9. Bissonette GB, Gentry RN, Padmala S, Pessoa L, Roesch MR. 2014. Impact of appetitive and aversive outcomes on brain responses: linking the animal and human literatures. Front. Syst. Neurosci. 8:24 [Google Scholar]
  10. Bocklisch C, Pascoli V, Wong JC, House DR, Yvon C. et al. 2013. Cocaine disinhibits dopamine neurons by potentiation of GABA transmission in the ventral tegmental area. Science 341:1521–25 [Google Scholar]
  11. Brischoux F, Chakraborty S, Brierley DI, Ungless MA. 2009. Phasic excitation of dopamine neurons in ventral VTA by noxious stimuli. PNAS 106:4894–99 [Google Scholar]
  12. Britt JP, Benaliouad F, McDevitt RA, Stuber GD, Wise RA, Bonci A. 2012. Synaptic and behavioral profile of multiple glutamatergic inputs to the nucleus accumbens. Neuron 76:790–803 [Google Scholar]
  13. Britt JP, Bonci A. 2013. Optogenetic interrogations of the neural circuits underlying addiction. Curr. Opin. Neurobiol. 23:539–45 [Google Scholar]
  14. Bromberg-Martin ES, Hikosaka O, Nakamura K. 2010a. Coding of task reward value in the dorsal raphe nucleus. J. Neurosci. 30:6262–72 [Google Scholar]
  15. Bromberg-Martin ES, Matsumoto M, Hikosaka O. 2010b. Distinct tonic and phasic anticipatory activity in lateral habenula and dopamine neurons. Neuron 67:144–55 [Google Scholar]
  16. Bromberg-Martin ES, Matsumoto M, Hikosaka O. 2010c. Dopamine in motivational control: rewarding, aversive, and alerting. Neuron 68:815–34 [Google Scholar]
  17. Bromberg-Martin ES, Matsumoto M, Nakahara H, Hikosaka O. 2010d. Multiple timescales of memory in lateral habenula and dopamine neurons. Neuron 67:499–510 [Google Scholar]
  18. Brown MT, Tan KR, O'Connor EC, Nikonenko I, Muller D, Lüscher C. 2012. Ventral tegmental area GABA projections pause accumbal cholinergic interneurons to enhance associative learning. Nature 492:452–56 [Google Scholar]
  19. Callaway EM, Luo L. 2015. Monosynaptic circuit tracing with glycoprotein-deleted rabies viruses. J. Neurosci. 35:8979–85 [Google Scholar]
  20. Carlezon WA Jr, Thomas MJ. 2009. Biological substrates of reward and aversion: a nucleus accumbens activity hypothesis. Neuropharmacology 56:Suppl. 1122–32 [Google Scholar]
  21. Challis C, Boulden J, Veerakumar A, Espallergues J, Vassoler FM. et al. 2013. Raphe GABAergic neurons mediate the acquisition of avoidance after social defeat. J. Neurosci. 33:13978–88 [Google Scholar]
  22. Chaudhury D, Walsh JJ, Friedman AK, Juarez B, Ku SM. et al. 2013. Rapid regulation of depression-related behaviours by control of midbrain dopamine neurons. Nature 493:532–36 [Google Scholar]
  23. Chen BT, Bowers MS, Martin M, Hopf FW, Guillory AM. et al. 2008. Cocaine but not natural reward self-administration nor passive cocaine infusion produces persistent LTP in the VTA. Neuron 59:288–97 [Google Scholar]
  24. Choi GB, Stettler DD, Kallman BR, Bhaskar ST, Fleischmann A, Axel R. 2011. Driving opposing behaviors with ensembles of piriform neurons. Cell 146:1004–15 [Google Scholar]
  25. Chowdhury R, Guitart-Masip M, Lambert C, Dayan P, Huys Q. et al. 2013. Dopamine restores reward prediction errors in old age. Nat. Neurosci. 16:648–53 [Google Scholar]
  26. Chuhma N, Tanaka KF, Hen R, Rayport S. 2011. Functional connectome of the striatal medium spiny neuron. J. Neurosci. 31:1183–92 [Google Scholar]
  27. Cohen JY, Amoroso MW, Uchida N. 2015. Serotonergic neurons signal reward and punishment on multiple timescales. eLife 4:e06346 [Google Scholar]
  28. Cohen JY, Haesler S, Vong L, Lowell BB, Uchida N. 2012. Neuron-type-specific signals for reward and punishment in the ventral tegmental area. Nature 482:85–88 [Google Scholar]
  29. Corbett D, Wise RA. 1980. Intracranial self-stimulation in relation to the ascending dopaminergic systems of the midbrain: a moveable electrode mapping study. Brain Res. 185:1–15 [Google Scholar]
  30. Covington HE 3rd, Lobo MK, Maze I, Vialou V, Hyman JM. et al. 2010. Antidepressant effect of optogenetic stimulation of the medial prefrontal cortex. J. Neurosci. 30:16082–90 [Google Scholar]
  31. D'Ardenne K, McClure SM, Nystrom LE, Cohen JD. 2008. BOLD responses reflecting dopaminergic signals in the human ventral tegmental area. Science 319:1264–67 [Google Scholar]
  32. Daw ND, Kakade S, Dayan P. 2002. Opponent interactions between serotonin and dopamine. Neural Netw. 15:603–16 [Google Scholar]
  33. Dayan P, Huys QJ. 2008. Serotonin, inhibition, and negative mood. PLOS Comput. Biol. 4:e4 [Google Scholar]
  34. Dayan P, Huys QJ. 2009. Serotonin in affective control. Annu. Rev. Neurosci. 32:95–126 [Google Scholar]
  35. Deakin JF, Graeff FG. 1991. 5-HT and mechanisms of defence. J. Psychopharmacol. 5:305–15 [Google Scholar]
  36. Di Chiara G. 2002. Nucleus accumbens shell and core dopamine: differential role in behavior and addiction. Behav. Brain Res. 137:75–114 [Google Scholar]
  37. Dias C, Feng J, Sun H, Shao NY, Mazei-Robison MS. et al. 2014. β-Catenin mediates stress resilience through Dicer1/microRNA regulation. Nature 516:51–55 [Google Scholar]
  38. Doherty MD, Gratton A. 1992. High-speed chronoamperometric measurements of mesolimbic and nigrostriatal dopamine release associated with repeated daily stress. Brain Res. 586:295–302 [Google Scholar]
  39. Dolen G, Darvishzadeh A, Huang KW, Malenka RC. 2013. Social reward requires coordinated activity of nucleus accumbens oxytocin and serotonin. Nature 501:179–84 [Google Scholar]
  40. Doya K. 1999. What are the computations of the cerebellum, the basal ganglia and the cerebral cortex?. Neural Netw. 12:961–74 [Google Scholar]
  41. Doya K. 2002. Metalearning and neuromodulation. Neural Netw. 15:495–506 [Google Scholar]
  42. Eshel N, Bukwich M, Rao V, Hemmelder V, Tian J, Uchida N. 2015. Arithmetic and local circuitry underlying dopamine prediction errors. Nature 525:243–46 [Google Scholar]
  43. Ferenczi EA, Zalocusky KA, Liston C, Grosenick L, Warden MR. et al. 2016. Prefrontal cortical regulation of brainwide circuit dynamics and reward-related behavior. Science 351:aac9698 [Google Scholar]
  44. Floresco SB. 2015. The nucleus accumbens: an interface between cognition, emotion, and action. Annu. Rev. Psychol. 66:25–52 [Google Scholar]
  45. Fonseca MS, Murakami M, Mainen ZF. 2015. Activation of dorsal raphe serotonergic neurons promotes waiting but is not reinforcing. Curr. Biol. 25:306–15 [Google Scholar]
  46. Fouriezos G, Wise RA. 1976. Pimozide-induced extinction of intracranial self-stimulation: Response patterns rule out motor or performance deficits. Brain Res. 103:377–80 [Google Scholar]
  47. Friedman A, Homma D, Gibb LG, Amemori K, Rubin SJ. et al. 2015. A corticostriatal path targeting striosomes controls decision-making under conflict. Cell 161:1320–33 [Google Scholar]
  48. Gao DM, Jeaugey L, Pollak P, Benabid AL. 1990. Intensity-dependent nociceptive responses from presumed dopaminergic neurons of the substantia nigra, pars compacta in the rat and their modification by lateral habenula inputs. Brain Res. 529:315–19 [Google Scholar]
  49. Gerfen CR. 1992. The neostriatal mosaic: multiple levels of compartmental organization. Trends Neurosci. 15:133–39 [Google Scholar]
  50. Gerfen CR, Surmeier DJ. 2011. Modulation of striatal projection systems by dopamine. Annu. Rev. Neurosci. 34:441–66 [Google Scholar]
  51. Gore F, Schwartz EC, Brangers BC, Aladi S, Stujenske JM. et al. 2015. Neural representations of unconditioned stimuli in basolateral amygdala mediate innate and learned responses. Cell 162:134–45 [Google Scholar]
  52. Goto Y, Grace AA. 2008. Limbic and cortical information processing in the nucleus accumbens. Trends Neurosci. 31:552–58 [Google Scholar]
  53. Gottfried JA, O'Doherty J, Dolan RJ. 2003. Encoding predictive reward value in human amygdala and orbitofrontal cortex. Science 301:1104–7 [Google Scholar]
  54. Gunaydin LA, Grosenick L, Finkelstein JC, Kauvar IV, Fenno LE. et al. 2014. Natural neural projection dynamics underlying social behavior. Cell 157:1535–51 [Google Scholar]
  55. Hayashi K, Nakao K, Nakamura K. 2015. Appetitive and aversive information coding in the primate dorsal raphe nucleus. J. Neurosci. 35:6195–208 [Google Scholar]
  56. Herkenham M, Nauta WJ. 1979. Efferent connections of the habenular nuclei in the rat. J. Comp. Neurol. 187:19–47 [Google Scholar]
  57. Hikosaka O. 2010. The habenula: from stress evasion to value-based decision-making. Nat. Rev. Neurosci. 11:503–13 [Google Scholar]
  58. Hirschfeld RM. 2000. History and evolution of the monoamine hypothesis of depression. J. Clin. Psychiatry 61:Suppl. 64–6 [Google Scholar]
  59. Hokfelt T, Arvidsson U, Cullheim S, Millhorn D, Nicholas AP. et al. 2000. Multiple messengers in descending serotonin neurons: localization and functional implications. J. Chem. Neuroanat. 18:75–86 [Google Scholar]
  60. Holroyd CB, Coles MG. 2002. The neural basis of human error processing: reinforcement learning, dopamine, and the error-related negativity. Psychol. Rev. 109:679–709 [Google Scholar]
  61. Hong S, Hikosaka O. 2014. Pedunculopontine tegmental nucleus neurons provide reward, sensorimotor, and alerting signals to midbrain dopamine neurons. Neuroscience 282C:139–55 [Google Scholar]
  62. Humphries MD, Prescott TJ. 2010. The ventral basal ganglia, a selection mechanism at the crossroads of space, strategy, and reward. Prog. Neurobiol. 90:385–417 [Google Scholar]
  63. Hyman SE, Malenka RC, Nestler EJ. 2006. Neural mechanisms of addiction: the role of reward-related learning and memory. Annu. Rev. Neurosci. 29:565–98 [Google Scholar]
  64. Ikemoto S. 2007. Dopamine reward circuitry: two projection systems from the ventral midbrain to the nucleus accumbens-olfactory tubercle complex. Brain Res. Rev. 56:27–78 [Google Scholar]
  65. Ikemoto S, Panksepp J. 1999. The role of nucleus accumbens dopamine in motivated behavior: a unifying interpretation with special reference to reward-seeking. Brain Res. Brain Res. Rev. 31:6–41 [Google Scholar]
  66. Ikemoto S, Wise RA. 2004. Mapping of chemical trigger zones for reward. Neuropharmacology 47:Suppl. 1190–201 [Google Scholar]
  67. Ilango A, Kesner AJ, Keller KL, Stuber GD, Bonci A, Ikemoto S. 2014. Similar roles of substantia nigra and ventral tegmental dopamine neurons in reward and aversion. J. Neurosci. 34:817–22 [Google Scholar]
  68. Inaba K, Mizuhiki T, Setogawa T, Toda K, Richmond BJ, Shidara M. 2013. Neurons in monkey dorsal raphe nucleus code beginning and progress of step-by-step schedule, reward expectation, and amount of reward outcome in the reward schedule task. J. Neurosci. 33:3477–91 [Google Scholar]
  69. Janak PH, Tye KM. 2015. From circuits to behaviour in the amygdala. Nature 517:284–92 [Google Scholar]
  70. Jennings JH, Ung RL, Resendez SL, Stamatakis AM, Taylor JG. et al. 2015. Visualizing hypothalamic network dynamics for appetitive and consummatory behaviors. Cell 160:516–27 [Google Scholar]
  71. Jhou TC, Geisler S, Marinelli M, Degarmo BA, Zahm DS. 2009. The mesopontine rostromedial tegmental nucleus: a structure targeted by the lateral habenula that projects to the ventral tegmental area of Tsai and substantia nigra compacta. J. Comp. Neurol. 513:566–96 [Google Scholar]
  72. Judge SJ, Gartside SE. 2006. Firing of 5-HT neurones in the dorsal and median raphe nucleus in vitro shows differential α1-adrenoceptor and 5-HT1A receptor modulation. Neurochem. Int. 48:100–7 [Google Scholar]
  73. Kamin LJ. 1968. Predictability, surprise, attention, and conditioning. Punishment and Aversive Behavior BA Campbell, RM Church 279–96 New York: Appleton-Century-Crofts [Google Scholar]
  74. Keiflin R, Janak PH. 2015. Dopamine prediction errors in reward learning and addiction: from theory to neural circuitry. Neuron 88:247–63 [Google Scholar]
  75. Khibnik LA, Beaumont M, Doyle M, Heshmati M, Slesinger PA. et al. 2015. Stress and cocaine trigger divergent and cell type-specific regulation of synaptic transmission at single spines in nucleus accumbens. Biol. Psychiatry. In press. doi: 10.1016/j.biopsych.2015.05.022
  76. Kim MA, Lee HS, Lee BY, Waterhouse BD. 2004. Reciprocal connections between subdivisions of the dorsal raphe and the nuclear core of the locus coeruleus in the rat. Brain Res. 1026:56–67 [Google Scholar]
  77. Kirouac GJ, Li S, Mabrouk G. 2004. GABAergic projection from the ventral tegmental area and substantia nigra to the periaqueductal gray region and the dorsal raphe nucleus. J. Comp. Neurol. 469:170–84 [Google Scholar]
  78. Kobayashi Y, Okada K. 2007. Reward prediction error computation in the pedunculopontine tegmental nucleus neurons. Ann. N.Y. Acad. Sci. 1104:310–23 [Google Scholar]
  79. Koya E, Hope BT. 2011. Cocaine and synaptic alterations in the nucleus accumbens. Biol. Psychiatry 69:1013–14 [Google Scholar]
  80. Krause M, German PW, Taha SA, Fields HL. 2010. A pause in nucleus accumbens neuron firing is required to initiate and maintain feeding. J. Neurosci. 30:4746–56 [Google Scholar]
  81. Kravitz AV, Freeze BS, Parker PR, Kay K, Thwin MT. et al. 2010. Regulation of parkinsonian motor behaviours by optogenetic control of basal ganglia circuitry. Nature 466:622–26 [Google Scholar]
  82. Kravitz AV, Tye LD, Kreitzer AC. 2012. Distinct roles for direct and indirect pathway striatal neurons in reinforcement. Nat. Neurosci. 15:816–18 [Google Scholar]
  83. Kringelbach ML. 2005. The human orbitofrontal cortex: linking reward to hedonic experience. Nat. Rev. Neurosci. 6:691–702 [Google Scholar]
  84. Kringelbach ML, Berridge KC. 2009. Towards a functional neuroanatomy of pleasure and happiness. Trends Cogn. Sci. 13:479–87 [Google Scholar]
  85. Kringelbach ML, O'Doherty J, Rolls ET, Andrews C. 2003. Activation of the human orbitofrontal cortex to a liquid food stimulus is correlated with its subjective pleasantness. Cereb. Cortex 13:1064–71 [Google Scholar]
  86. Kupchik YM, Brown RM, Heinsbroek JA, Lobo MK, Schwartz DJ, Kalivas PW. 2015. Coding the direct/indirect pathways by D1 and D2 receptors is not valid for accumbens projections. Nat. Neurosci. 18:1230–32 [Google Scholar]
  87. Kvitsiani D, Ranade S, Hangya B, Taniguchi H, Huang JZ, Kepecs A. 2013. Distinct behavioural and network correlates of two interneuron types in prefrontal cortex. Nature 498:363–66 [Google Scholar]
  88. Lammel S, Ion DI, Roeper J, Malenka RC. 2011. Projection-specific modulation of dopamine neuron synapses by aversive and rewarding stimuli. Neuron 70:855–62 [Google Scholar]
  89. Lammel S, Lim BK, Malenka RC. 2014. Reward and aversion in a heterogeneous midbrain dopamine system. Neuropharmacology 76:Part B351–59 [Google Scholar]
  90. Lammel S, Lim BK, Ran C, Huang KW, Betley MJ. et al. 2012. Input-specific control of reward and aversion in the ventral tegmental area. Nature 491:212–17 [Google Scholar]
  91. Le Merrer J, Becker JA, Befort K, Kieffer BL. 2009. Reward processing by the opioid system in the brain. Physiol. Rev. 89:1379–412 [Google Scholar]
  92. Lee BR, Ma YY, Huang YH, Wang X, Otaka M. et al. 2013. Maturation of silent synapses in amygdala-accumbens projection contributes to incubation of cocaine craving. Nat. Neurosci. 16:1644–51 [Google Scholar]
  93. Lerner TN, Shilyansky C, Davidson TJ, Evans KE, Beier KT. et al. 2015. Intact-brain analyses reveal distinct information carried by SNc dopamine subcircuits. Cell 162:635–47 [Google Scholar]
  94. Li B, Piriz J, Mirrione M, Chung C, Proulx CD. et al. 2011. Synaptic potentiation onto habenula neurons in the learned helplessness model of depression. Nature 470:535–39 [Google Scholar]
  95. Li K, Zhou T, Liao L, Yang Z, Wong C. et al. 2013a. βCaMKII in lateral habenula mediates core symptoms of depression. Science 341:1016–20 [Google Scholar]
  96. Li Y, Dalphin N, Hyland BI. 2013b. Association with reward negatively modulates short latency phasic conditioned responses of dorsal raphe nucleus neurons in freely moving rats. J. Neurosci. 33:5065–78 [Google Scholar]
  97. Li Y, Zhong W, Wang D, Feng Q, Liu Z. et al. 2016. Serotonin neurons in the dorsal raphe nucleus encode reward signals. Nat. Commun. 7:10503 [Google Scholar]
  98. Lim BK, Huang KW, Grueter BA, Rothwell PE, Malenka RC. 2012. Anhedonia requires MC4R-mediated synaptic adaptations in nucleus accumbens. Nature 487:183–89 [Google Scholar]
  99. Lin D, Boyle MP, Dollar P, Lee H, Lein ES. et al. 2011. Functional identification of an aggression locus in the mouse hypothalamus. Nature 470:221–26 [Google Scholar]
  100. Liu Z, Zhou J, Li Y, Hu F, Lu Y. et al. 2014. Dorsal raphe neurons signal reward through 5-HT and glutamate. Neuron 81:1360–74 [Google Scholar]
  101. Lobo MK, Covington HE 3rd, Chaudhury D, Friedman AK, Sun H. et al. 2010. Cell type specific loss of BDNF signaling mimics optogenetic control of cocaine reward. Science 330:385–90 [Google Scholar]
  102. Louilot A, Le Moal M, Simon H. 1986. Differential reactivity of dopaminergic neurons in the nucleus accumbens in response to different behavioral situations. An in vivo voltammetric study in free moving rats. Brain Res. 397:395–400 [Google Scholar]
  103. Luo M, Zhou J, Liu Z. 2015. Reward processing by the dorsal raphe nucleus: 5-HT and beyond. Learn. Mem. 22:452–60 [Google Scholar]
  104. Lüscher C, Malenka RC. 2011. Drug-evoked synaptic plasticity in addiction: from molecular changes to circuit remodeling. Neuron 69:650–63 [Google Scholar]
  105. Macoveanu J. 2014. Serotonergic modulation of reward and punishment: evidence from pharmacological fMRI studies. Brain Res. 1556:19–27 [Google Scholar]
  106. Mameli M, Halbout B, Creton C, Engblom D, Parkitna JR. et al. 2009. Cocaine-evoked synaptic plasticity: Persistence in the VTA triggers adaptations in the NAc. Nat. Neurosci. 12:1036–41 [Google Scholar]
  107. Matsumoto M, Hikosaka O. 2007. Lateral habenula as a source of negative reward signals in dopamine neurons. Nature 447:1111–15 [Google Scholar]
  108. Matsumoto M, Hikosaka O. 2009a. Representation of negative motivational value in the primate lateral habenula. Nat. Neurosci. 12:77–84 [Google Scholar]
  109. Matsumoto M, Hikosaka O. 2009b. Two types of dopamine neuron distinctly convey positive and negative motivational signals. Nature 459:837–41 [Google Scholar]
  110. Matsumoto M, Matsumoto K, Abe H, Tanaka K. 2007. Medial prefrontal cell activity signaling prediction errors of action values. Nat. Neurosci. 10:647–56 [Google Scholar]
  111. McClure SM, Daw ND, Montague PR. 2003. A computational substrate for incentive salience. Trends Neurosci. 26:423–28 [Google Scholar]
  112. McDevitt RA, Tiran-Cappello A, Shen H, Balderas I, Britt JP. et al. 2014. Serotonergic versus nonserotonergic dorsal raphe projection neurons: differential participation in reward circuitry. Cell Rep. 8:1857–69 [Google Scholar]
  113. Menegas W, Bergan JF, Ogawa SK, Isogai Y, Umadevi Venkataraju K. et al. 2015. Dopamine neurons projecting to the posterior striatum form an anatomically distinct subclass. eLife 4:e10032 [Google Scholar]
  114. Miyazaki K, Miyazaki KW, Doya K. 2011. Activation of dorsal raphe serotonin neurons underlies waiting for delayed rewards. J. Neurosci. 31:469–79 [Google Scholar]
  115. Miyazaki KW, Miyazaki K, Tanaka KF, Yamanaka A, Takahashi A. et al. 2014. Optogenetic activation of dorsal raphe serotonin neurons enhances patience for future rewards. Curr. Biol. 24:2033–40 [Google Scholar]
  116. Monosov IE, Hikosaka O. 2012. Regionally distinct processing of rewards and punishments by the primate ventromedial prefrontal cortex. J. Neurosci. 32:10318–30 [Google Scholar]
  117. Moorman DE, Aston-Jones G. 2015. Prefrontal neurons encode context-based response execution and inhibition in reward seeking and extinction. PNAS 112:9472–77 [Google Scholar]
  118. Morgan MA, LeDoux JE. 1995. Differential contribution of dorsal and ventral medial prefrontal cortex to the acquisition and extinction of conditioned fear in rats. Behav. Neurosci. 109:681–88 [Google Scholar]
  119. Morris JS, Smith KA, Cowen PJ, Friston KJ, Dolan RJ. 1999. Covariation of activity in habenula and dorsal raphe nuclei following tryptophan depletion. NeuroImage 10:163–72 [Google Scholar]
  120. Nader K, Schafe GE, LeDoux JE. 2000. The labile nature of consolidation theory. Nat. Rev. Neurosci. 1:216–19 [Google Scholar]
  121. Nakamura K, Matsumoto M, Hikosaka O. 2008. Reward-dependent modulation of neuronal activity in the primate dorsal raphe nucleus. J. Neurosci. 28:5331–43 [Google Scholar]
  122. Nakamura K, Ono T. 1986. Lateral hypothalamus neuron involvement in integration of natural and artificial rewards and cue signals. J. Neurophysiol. 55:163–81 [Google Scholar]
  123. Namburi P, Al-Hasani R, Calhoon GG, Bruchas MR, Tye KM. 2015a. Architectural representation of valence in the limbic system. Neuropsychopharmacology. In press. doi: 10.1038/npp.2015.358
  124. Namburi P, Beyeler A, Yorozu S, Calhoon GG, Halbert SA. et al. 2015b. A circuit mechanism for differentiating positive and negative associations. Nature 520:675–78 [Google Scholar]
  125. Nestler EJ. 2015. ΔFosB: a transcriptional regulator of stress and antidepressant responses. Eur. J. Pharmacol. 753:66–72 [Google Scholar]
  126. Nicola SM, Surmeier J, Malenka RC. 2000. Dopaminergic modulation of neuronal excitability in the striatum and nucleus accumbens. Annu. Rev. Neurosci. 23:185–215 [Google Scholar]
  127. Nieh EH, Matthews GA, Allsop SA, Presbrey KN, Leppla CA. et al. 2015. Decoding neural circuits that control compulsive sucrose seeking. Cell 160:528–41 [Google Scholar]
  128. Niv Y, Joel D, Dayan P. 2006. A normative perspective on motivation. Trends Cogn. Sci. 10:375–81 [Google Scholar]
  129. Ogawa SK, Cohen JY, Hwang D, Uchida N, Watabe-Uchida M. 2014. Organization of monosynaptic inputs to the serotonin and dopamine neuromodulatory systems. Cell Rep. 8:1105–18 [Google Scholar]
  130. Olds J, Milner P. 1954. Positive reinforcement produced by electrical stimulation of septal area and other regions of rat brain. J. Comp. Physiol. Psychol. 47:419–27 [Google Scholar]
  131. Olds J, Travis RP. 1960. Effects of chlorpromazine, meprobamate, pentobarbital and morphine on self-stimulation. J. Pharmacol. Exp. Ther. 128:397–404 [Google Scholar]
  132. Padoa-Schioppa C, Assad JA. 2006. Neurons in the orbitofrontal cortex encode economic value. Nature 441:223–26 [Google Scholar]
  133. Pan WX, Hyland BI. 2005. Pedunculopontine tegmental nucleus controls conditioned responses of midbrain dopamine neurons in behaving rats. J. Neurosci. 25:4725–32 [Google Scholar]
  134. Pascoli V, Terrier J, Hiver A, Lüscher C. 2015. Sufficiency of mesolimbic dopamine neuron stimulation for the progression to addiction. Neuron 88:1054–66 [Google Scholar]
  135. Pascoli V, Turiault M, Lüscher C. 2012. Reversal of cocaine-evoked synaptic potentiation resets drug-induced adaptive behaviour. Nature 481:71–75 [Google Scholar]
  136. Paton JJ, Belova MA, Morrison SE, Salzman CD. 2006. The primate amygdala represents the positive and negative value of visual stimuli during learning. Nature 439:865–70 [Google Scholar]
  137. Peng Y, Gillis-Smith S, Jin H, Trankner D, Ryba NJ, Zuker CS. 2015. Sweet and bitter taste in the brain of awake behaving animals. Nature 527:512–15 [Google Scholar]
  138. Perreau-Linck E, Beauregard M, Gravel P, Paquette V, Soucy JP. et al. 2007. In vivo measurements of brain trapping of C-labelled α-methyl-L-tryptophan during acute changes in mood states. J. Psychiatry Neurosci. 32:430–34 [Google Scholar]
  139. Pezze MA, Feldon J. 2004. Mesolimbic dopaminergic pathways in fear conditioning. Prog. Neurobiol. 74:301–20 [Google Scholar]
  140. Pignatelli M, Bonci A. 2015. Role of dopamine neurons in reward and aversion: a synaptic plasticity perspective. Neuron 86:1145–57 [Google Scholar]
  141. Pollak Dorocic I, Furth D, Xuan Y, Johansson Y, Pozzi L. et al. 2014. A whole-brain atlas of inputs to serotonergic neurons of the dorsal and median raphe nuclei. Neuron 83:663–78 [Google Scholar]
  142. Proulx CD, Hikosaka O, Malinow R. 2014. Reward processing by the lateral habenula in normal and depressive behaviors. Nat. Neurosci. 17:1146–52 [Google Scholar]
  143. Qi J, Zhang S, Wang HL, Wang H, de Jesus Aceves Buendia J. et al. 2014. A glutamatergic reward input from the dorsal raphe to ventral tegmental area dopamine neurons. Nat. Commun. 5:5390 [Google Scholar]
  144. Quirk GJ, Beer JS. 2006. Prefrontal involvement in the regulation of emotion: convergence of rat and human studies. Curr. Opin. Neurobiol. 16:723–27 [Google Scholar]
  145. Ramirez S, Liu X, MacDonald CJ, Moffa A, Zhou J. et al. 2015. Activating positive memory engrams suppresses depression-like behaviour. Nature 522:335–39 [Google Scholar]
  146. Ranade SP, Mainen ZF. 2009. Transient firing of dorsal raphe neurons encodes diverse and specific sensory, motor, and reward events. J. Neurophysiol. 102:3026–37 [Google Scholar]
  147. Redondo RL, Kim J, Arons AL, Ramirez S, Liu X, Tonegawa S. 2014. Bidirectional switch of the valence associated with a hippocampal contextual memory engram. Nature 513:426–30 [Google Scholar]
  148. Roberts D, Zito K. 1987. Interpretation of lesion effects on stimulant self-administration. Methods of Assessing the Reinforcing Properties of Abused Drugs MA Bozarth 87–103 Berlin: Springer [Google Scholar]
  149. Roberts DC, Corcoran ME, Fibiger HC. 1977. On the role of ascending catecholaminergic systems in intravenous self-administration of cocaine. Pharmacol. Biochem. Behav. 6:615–20 [Google Scholar]
  150. Roesch MR, Olson CR. 2004. Neuronal activity related to reward value and motivation in primate frontal cortex. Science 304:307–10 [Google Scholar]
  151. Roesch MR, Taylor AR, Schoenbaum G. 2006. Encoding of time-discounted rewards in orbitofrontal cortex is independent of value representation. Neuron 51:509–20 [Google Scholar]
  152. Roitman MF, Wheeler RA, Carelli RM. 2005. Nucleus accumbens neurons are innately tuned for rewarding and aversive taste stimuli, encode their predictors, and are linked to motor output. Neuron 45:587–97 [Google Scholar]
  153. Roitman MF, Wheeler RA, Tiesinga PH, Roitman JD, Carelli RM. 2010. Hedonic and nucleus accumbens neural responses to a natural reward are regulated by aversive conditioning. Learn. Mem. 17:539–46 [Google Scholar]
  154. Roll SK. 1970. Intracranial self-stimulation and wakefulness: Effect of manipulating ambient brain catecholamines. Science 168:1370–72 [Google Scholar]
  155. Rudebeck PH, Walton ME, Smyth AN, Bannerman DM, Rushworth MF. 2006. Separate neural pathways process different decision costs. Nat. Neurosci. 9:1161–68 [Google Scholar]
  156. Russo SJ, Dietz DM, Dumitriu D, Morrison JH, Malenka RC, Nestler EJ. 2010. The addicted synapse: mechanisms of synaptic and structural plasticity in nucleus accumbens. Trends Neurosci. 33:267–76 [Google Scholar]
  157. Russo SJ, Nestler EJ. 2013. The brain reward circuitry in mood disorders. Nat. Rev. Neurosci. 14:609–25 [Google Scholar]
  158. Saal D, Dong Y, Bonci A, Malenka RC. 2003. Drugs of abuse and stress trigger a common synaptic adaptation in dopamine neurons. Neuron 37:577–82 [Google Scholar]
  159. Salamone JD. 1994. The involvement of nucleus accumbens dopamine in appetitive and aversive motivation. Behav. Brain Res. 61:117–33 [Google Scholar]
  160. Salamone JD. 1996. The behavioral neurochemistry of motivation: methodological and conceptual issues in studies of the dynamic activity of nucleus accumbens dopamine. J. Neurosci. Methods 64:137–49 [Google Scholar]
  161. Salzman CD, Paton JJ, Belova MA, Morrison SE. 2007. Flexible neural representations of value in the primate brain. Ann. N.Y. Acad. Sci. 1121:336–54 [Google Scholar]
  162. Savitz J, Lucki I, Drevets WC. 2009. 5-HT1A receptor function in major depressive disorder. Prog. Neurobiol. 88:17–31 [Google Scholar]
  163. Schultz W. 1998. Predictive reward signal of dopamine neurons. J. Neurophysiol. 80:1–27 [Google Scholar]
  164. Schultz W. 2007a. Behavioral dopamine signals. Trends Neurosci. 30:203–10 [Google Scholar]
  165. Schultz W. 2007b. Multiple dopamine functions at different time courses. Annu. Rev. Neurosci. 30:259–88 [Google Scholar]
  166. Schultz W. 2010. Dopamine signals for reward value and risk: basic and recent data. Behav. Brain Funct. 6:24 [Google Scholar]
  167. Schultz W, Dayan P, Montague PR. 1997. A neural substrate of prediction and reward. Science 275:1593–99 [Google Scholar]
  168. Schwarz LA, Miyamichi K, Gao XJ, Beier KT, Weissbourd B. et al. 2015. Viral-genetic tracing of the input-output organization of a central noradrenaline circuit. Nature 524:88–92 [Google Scholar]
  169. Schweimer JV, Ungless MA. 2010. Phasic responses in dorsal raphe serotonin neurons to noxious stimuli. Neuroscience 171:1209–15 [Google Scholar]
  170. Sesack SR, Grace AA. 2010. Cortico-basal ganglia reward network: microcircuitry. Neuropsychopharmacology 35:27–47 [Google Scholar]
  171. Seymour B, Daw ND, Roiser JP, Dayan P, Dolan R. 2012. Serotonin selectively modulates reward value in human decision-making. J. Neurosci. 32:5833–42 [Google Scholar]
  172. Shabel SJ, Janak PH. 2009. Substantial similarity in amygdala neuronal activity during conditioned appetitive and aversive emotional arousal. PNAS 106:15031–36 [Google Scholar]
  173. Shabel SJ, Proulx CD, Piriz J, Malinow R. 2014. Mood regulation. GABA/glutamate co-release controls habenula output and is modified by antidepressant treatment. Science 345:1494–98 [Google Scholar]
  174. Shabel SJ, Proulx CD, Trias A, Murphy RT, Malinow R. 2012. Input to the lateral habenula from the basal ganglia is excitatory, aversive, and suppressed by serotonin. Neuron 74:475–81 [Google Scholar]
  175. Sheehan TP, Chambers RA, Russell DS. 2004. Regulation of affect by the lateral septum: implications for neuropsychiatry. Brain Res. Brain Res. Rev. 46:71–117 [Google Scholar]
  176. Shumake J, Edwards E, Gonzalez-Lima F. 2003. Opposite metabolic changes in the habenula and ventral tegmental area of a genetic model of helpless behavior. Brain Res. 963:274–81 [Google Scholar]
  177. Sienkiewicz-Jarosz H, Scinska A, Swiecicki L, Lipczynska-Lojkowska W, Kuran W. et al. 2013. Sweet liking in patients with Parkinson's disease. J. Neurol. Sci. 329:17–22 [Google Scholar]
  178. Simon H, Le Moal M, Cardo B. 1976. Intracranial self-stimulation from the dorsal raphe nucleus of the rat: effects of the injection of para-chlorophenylalanine and of alpha-methylparatyrosine. Behav. Biol. 16:353–64 [Google Scholar]
  179. Sora I, Hall FS, Andrews AM, Itokawa M, Li XF. et al. 2001. Molecular mechanisms of cocaine reward: Combined dopamine and serotonin transporter knockouts eliminate cocaine place preference. PNAS 98:5300–5 [Google Scholar]
  180. Stamatakis AM, Stuber GD. 2012. Activation of lateral habenula inputs to the ventral midbrain promotes behavioral avoidance. Nat. Neurosci. 15:1105–7 [Google Scholar]
  181. Stefanik MT, Moussawi K, Kupchik YM, Smith KC, Miller RL. et al. 2013. Optogenetic inhibition of cocaine seeking in rats. Addict. Biol. 18:50–53 [Google Scholar]
  182. Stein L. 1962. Effects and interactions of imipramine, chlorpromazine, reserpine and amphetamine on self-stimulation: possible neurophysiological basis of depression. Recent Advances in Biological Psychiatry IV J Wortis, 4288–309 New York: Plenum [Google Scholar]
  183. Stein L. 1968. Chemistry of reward and punishment. Psychopharmacology: A Review of Progress, 1957–1967 DH Efron 105–23 Washington, DC: Am. Coll. Neuropsychopharmacol. [Google Scholar]
  184. Steinberg EE, Keiflin R, Boivin JR, Witten IB, Deisseroth K, Janak PH. 2013. A causal link between prediction errors, dopamine neurons and learning. Nat. Neurosci. 16:966–73 [Google Scholar]
  185. Sternson SM, Nicholas Betley J, Cao ZF. 2013. Neural circuits and motivational processes for hunger. Curr. Opin. Neurobiol. 23:353–60 [Google Scholar]
  186. Stuber GD, Hnasko TS, Britt JP, Edwards RH, Bonci A. 2010. Dopaminergic terminals in the nucleus accumbens but not the dorsal striatum corelease glutamate. J. Neurosci. 30:8229–33 [Google Scholar]
  187. Stuber GD, Sparta DR, Stamatakis AM, van Leeuwen WA, Hardjoprajitno JE. et al. 2011. Excitatory transmission from the amygdala to nucleus accumbens facilitates reward seeking. Nature 475:377–80 [Google Scholar]
  188. Stuber GD, Wise RA. 2016. Lateral hypothalamic circuits for feeding and reward. Nat. Neurosci. 19:198–205 [Google Scholar]
  189. Sulzer D, Joyce MP, Lin L, Geldwert D, Haber SN. et al. 1998. Dopamine neurons make glutamatergic synapses in vitro. J. Neurosci. 18:4588–602 [Google Scholar]
  190. Suri RE. 2002. TD models of reward predictive responses in dopamine neurons. Neural Netw. 15:523–33 [Google Scholar]
  191. Svenningsson P, Chergui K, Rachleff I, Flajolet M, Zhang X. et al. 2006. Alterations in 5-HT1B receptor function by p11 in depression-like states. Science 311:77–80 [Google Scholar]
  192. Tai LH, Lee AM, Benavidez N, Bonci A, Wilbrecht L. 2012. Transient stimulation of distinct subpopulations of striatal neurons mimics changes in action value. Nat. Neurosci. 15:1281–89 [Google Scholar]
  193. Takahashi YK, Roesch MR, Stalnaker TA, Haney RZ, Calu DJ. et al. 2009. The orbitofrontal cortex and ventral tegmental area are necessary for learning from unexpected outcomes. Neuron 62:269–80 [Google Scholar]
  194. Takahashi YK, Roesch MR, Wilson RC, Toreson K, O'Donnell P. et al. 2011. Expectancy-related changes in firing of dopamine neurons depend on orbitofrontal cortex. Nat. Neurosci. 14:1590–97 [Google Scholar]
  195. Tan KR, Yvon C, Turiault M, Mirzabekov JJ, Doehner J. et al. 2012. GABA neurons of the VTA drive conditioned place aversion. Neuron 73:1173–83 [Google Scholar]
  196. Tecuapetla F, Patel JC, Xenias H, English D, Tadros I. et al. 2010. Glutamatergic signaling by mesolimbic dopamine neurons in the nucleus accumbens. J. Neurosci. 30:7105–10 [Google Scholar]
  197. Tian J, Uchida N. 2015. Habenula lesions reveal that multiple mechanisms underlie dopamine prediction errors. Neuron 87:1304–16 [Google Scholar]
  198. Tindell AJ, Smith KS, Pecina S, Berridge KC, Aldridge JW. 2006. Ventral pallidum firing codes hedonic reward: When a bad taste turns good. J. Neurophysiol. 96:2399–409 [Google Scholar]
  199. Tost H, Champagne FA, Meyer-Lindenberg A. 2015. Environmental influence in the brain, human welfare and mental health. Nat. Neurosci. 18:1421–31 [Google Scholar]
  200. Tremblay L, Schultz W. 1999. Relative reward preference in primate orbitofrontal cortex. Nature 398:704–8 [Google Scholar]
  201. Tritsch NX, Ding JB, Sabatini BL. 2012. Dopaminergic neurons inhibit striatal output through non-canonical release of GABA. Nature 490:262–66 [Google Scholar]
  202. Tsai HC, Zhang F, Adamantidis A, Stuber GD, Bonci A. et al. 2009. Phasic firing in dopaminergic neurons is sufficient for behavioral conditioning. Science 324:1080–84 [Google Scholar]
  203. Tye KM, Mirzabekov JJ, Warden MR, Ferenczi EA, Tsai HC. et al. 2013. Dopamine neurons modulate neural encoding and expression of depression-related behaviour. Nature 493:537–41 [Google Scholar]
  204. Tye NC, Everitt BJ, Iversen SD. 1977. 5-Hydroxytryptamine and punishment. Nature 268:741–43 [Google Scholar]
  205. Ungless MA, Magill PJ, Bolam JP. 2004. Uniform inhibition of dopamine neurons in the ventral tegmental area by aversive stimuli. Science 303:2040–42 [Google Scholar]
  206. Ungless MA, Whistler JL, Malenka RC, Bonci A. 2001. Single cocaine exposure in vivo induces long-term potentiation in dopamine neurons. Nature 411:583–87 [Google Scholar]
  207. van Duuren E, van der Plasse G, Lankelma J, Joosten RN, Feenstra MG, Pennartz CM. 2009. Single-cell and population coding of expected reward probability in the orbitofrontal cortex of the rat. J. Neurosci. 29:8965–76 [Google Scholar]
  208. van Zessen R, Phillips JL, Budygin EA, Stuber GD. 2012. Activation of VTA GABA neurons disrupts reward consumption. Neuron 73:1184–94 [Google Scholar]
  209. Waelti P, Dickinson A, Schultz W. 2001. Dopamine responses comply with basic assumptions of formal learning theory. Nature 412:43–48 [Google Scholar]
  210. Watabe-Uchida M, Zhu L, Ogawa SK, Vamanrao A, Uchida N. 2012. Whole-brain mapping of direct inputs to midbrain dopamine neurons. Neuron 74:858–73 [Google Scholar]
  211. Weissbourd B, Ren J, DeLoach KE, Guenthner CJ, Miyamichi K, Luo L. 2014. Presynaptic partners of dorsal raphe serotonergic and GABAergic neurons. Neuron 83:645–62 [Google Scholar]
  212. Williams E, Stewart-Knox B, Helander A, McConville C, Bradbury I, Rowland I. 2006. Associations between whole-blood serotonin and subjective mood in healthy male volunteers. Biol. Psychol. 71:171–74 [Google Scholar]
  213. Wilson CJ, Kawaguchi Y. 1996. The origins of two-state spontaneous membrane potential fluctuations of neostriatal spiny neurons. J. Neurosci. 16:2397–410 [Google Scholar]
  214. Winston JS, Gottfried JA, Kilner JM, Dolan RJ. 2005. Integrated neural representations of odor intensity and affective valence in human amygdala. J. Neurosci. 25:8903–7 [Google Scholar]
  215. Wise RA. 1978. Catecholamine theories of reward: a critical review. Brain Res. 152:215–47 [Google Scholar]
  216. Wise RA. 1996. Addictive drugs and brain stimulation reward. Annu. Rev. Neurosci. 19:319–40 [Google Scholar]
  217. Wise RA. 2004. Dopamine, learning and motivation. Nat. Rev. Neurosci. 5:483–94 [Google Scholar]
  218. Wise RA. 2008. Dopamine and reward: the anhedonia hypothesis 30 years on. Neurotoxicity Res. 14:169–83 [Google Scholar]
  219. Wise RA, Raptis L. 1986. Effects of naloxone and pimozide on initiation and maintenance measures of free feeding. Brain Res. 368:62–68 [Google Scholar]
  220. Wise RA, Rompre PP. 1989. Brain dopamine and reward. Annu. Rev. Psychol. 40:191–225 [Google Scholar]
  221. Xiu J, Zhang Q, Zhou T, Zhou TT, Chen Y, Hu H. 2014. Visualizing an emotional valence map in the limbic forebrain by TAI-FISH. Nat. Neurosci. 17:1552–59 [Google Scholar]
  222. Yan J, Scott TR. 1996. The effect of satiety on responses of gustatory neurons in the amygdala of alert cynomolgus macaques. Brain Res. 740:193–200 [Google Scholar]
  223. Yizhar O, Fenno LE, Prigge M, Schneider F, Davidson TJ. et al. 2011. Neocortical excitation/inhibition balance in information processing and social dysfunction. Nature 477:171–78 [Google Scholar]
  224. Young AM, Joseph MH, Gray JA. 1993. Latent inhibition of conditioned dopamine release in rat nucleus accumbens. Neuroscience 54:5–9 [Google Scholar]
  225. Zhou J, Jia C, Feng Q, Bao J, Luo M. 2015. Prospective coding of dorsal raphe reward signals by the orbitofrontal cortex. J. Neurosci. 35:2717–30 [Google Scholar]
  226. Zhu Y, Wienecke CF, Nachtrab G, Chen X. 2016. A thalamic input to the nucleus accumbens mediates opiate dependence. Nature 530:219–22 [Google Scholar]
  227. Ziv Y, Burns LD, Cocker ED, Hamel EO, Ghosh KK. et al. 2013. Long-term dynamics of CA1 hippocampal place codes. Nat. Neurosci. 16:264–66 [Google Scholar]
  228. Zweifel LS, Fadok JP, Argilli E, Garelick MG, Jones GL. et al. 2011. Activation of dopamine neurons is critical for aversive conditioning and prevention of generalized anxiety. Nat. Neurosci. 14:620–26 [Google Scholar]
/content/journals/10.1146/annurev-neuro-070815-014106
Loading
/content/journals/10.1146/annurev-neuro-070815-014106
Loading

Data & Media loading...

  • Article Type: Review Article
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error