Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review Article
  • Published:

Striatal circuits for reward learning and decision-making

Abstract

The striatum is essential for learning which actions lead to reward and for implementing those actions. Decades of experimental and theoretical work have led to several influential theories and hypotheses about how the striatal circuit mediates these functions. However, owing to technical limitations, testing these hypotheses rigorously has been difficult. In this Review, we briefly describe some of the classic ideas of striatal function. We then review recent studies in rodents that take advantage of optical and genetic methods to test these classic ideas by recording and manipulating identified cell types within the circuit. This new body of work has provided experimental support of some longstanding ideas about the striatal circuit and has uncovered critical aspects of the classic view that are incorrect or incomplete.

This is a preview of subscription content, access via your institution

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: Heterogeneity of midbrain dopamine neurons.
Fig. 2: Direct and indirect pathway regulation of behaviour.
Fig. 3: Cholinergic interneurons modulate synaptic plasticity and cocaine context extinction learning.
Fig. 4: Glutamatergic inputs to the striatum.

Similar content being viewed by others

References

  1. Alexander, G. E., DeLong, M. R. & Strick, P. L. Parallel organization of functionally segregated circuits linking basal ganglia and cortex. Annu. Rev. Neurosci. 9, 357–381 (1986).

    CAS  PubMed  Google Scholar 

  2. Alexander, G. E. & Crutcher, M. D. Functional architecture of basal ganglia circuits: neural substrates of parallel processing. Trends Neurosci. 13, 266–271 (1990).

    CAS  PubMed  Google Scholar 

  3. Redgrave, P. et al. Goal-directed and habitual control in the basal ganglia: implications for Parkinson’s disease. Nat. Rev. Neurosci. 11, 760–772 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  4. Gerfen, C. R. & Bolam, J. P. in Handbook of Basal Ganglia Structure and Function 2nd edn Vol. 24 (eds Steiner, H. & Tseng, K. Y.) 3–32 (Elsevier, 2016).

  5. Loopuijt, L. D. & van der Kooy, D. Organization of the striatum: collateralization of its efferent axons. Brain Res. 348, 86–99 (1985).

    CAS  PubMed  Google Scholar 

  6. Gerfen, C. R. & Scott Young, W. Distribution of striatonigral and striatopallidal peptidergic neurons in both patch and matrix compartments: an in situ hybridization histochemistry and fluorescent retrograde tracing study. Brain Res. 460, 161–167 (1988).

    CAS  PubMed  Google Scholar 

  7. Kawaguchi, Y., Wilson, C. J. & Emson, P. C. Projection subtypes of rat neostriatal matrix cells revealed by intracellular injection of biocytin. J. Neurosci. 10, 3421–3438 (1990).

    CAS  PubMed  Google Scholar 

  8. Gerfen, C. R. et al. D1 and D2 dopamine receptor-regulated gene expression of striatonigral and striatopallidal neurons. Science 250, 1429–1432 (1990).

    CAS  PubMed  Google Scholar 

  9. Wu, Y., Richard, S. & Parent, A. The organization of the striatal output system: a single-cell juxtacellular labeling study in the rat. Neurosci. Res. 38, 49–62 (2000).

    CAS  PubMed  Google Scholar 

  10. Albin, R. L., Young, A. B. & Penney, J. B. The functional anatomy of basal ganglia disorders. Trends Neurosci. 12, 366–375 (1989).

    CAS  PubMed  Google Scholar 

  11. Chevalier, G. & Deniau, J. M. Disinhibition as a basic process in the expression of striatal functions. Trends Neurosci. 13, 277–280 (1990).

    CAS  PubMed  Google Scholar 

  12. DeLong, M. R. Primate models of movement disorders of basal ganglia origin. Trends Neurosci. 13, 281–285 (1990).

    CAS  PubMed  Google Scholar 

  13. Mink, J. W. The basal ganglia: focused selection and inhibition of competing motor programs. Prog. Neurobiol. 50, 381–425 (1996).

    CAS  PubMed  Google Scholar 

  14. Lanciego, J. L., Luquin, N. & Obeso, J. A. Functional neuroanatomy of the basal ganglia. Cold Spring Harb. Perspect. Med. 2, a009621 (2012).

    PubMed  PubMed Central  Google Scholar 

  15. Nelson, A. B. & Kreitzer, A. C. Reassessing models of basal ganglia function and dysfunction. Annu. Rev. Neurosci. 37, 117–135 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  16. Bolam, J. P., Wainer, B. H. & Smith, A. D. Characterization of cholinergic neurons in the rat neostriatum. A combination of choline acetyltransferase immunocytochemistry, Golgi-impregnation and electron microscopy. Neuroscience 12, 711–718 (1984).

    CAS  PubMed  Google Scholar 

  17. Burke, D. A., Rotstein, H. G. & Alvarez, V. A. Striatal local circuitry: a new framework for lateral inhibition. Neuron 96, 267–284 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  18. Tepper, J. M. & Koós, T. in Handbook of Basal Ganglia Structure and Function 2nd edn Vol. 24 (eds Steiner, H. & Tseng, K. Y.) 157–178 (Elsevier, 2016).

  19. Berke, J. D. Functional properties of striatal fast-spiking interneurons. Front. Syst. Neurosci. 5, 45 (2011).

    PubMed  PubMed Central  Google Scholar 

  20. Beckstead, R. M., Domesick, V. B. & Nauta, W. J. Efferent connections of the substantia nigra and ventral tegmental area in the rat. Brain Res. 175, 191–217 (1979).

    CAS  PubMed  Google Scholar 

  21. Swanson, L. W. The projections of the ventral tegmental area and adjacent regions: a combined fluorescent retrograde tracer and immunofluorescence study in the rat. Brain Res. Bull. 9, 321–353 (1982).

    CAS  PubMed  Google Scholar 

  22. Lammel, S. et al. Unique properties of mesoprefrontal neurons within a dual mesocorticolimbic dopamine system. Neuron 57, 760–773 (2008).

    CAS  PubMed  Google Scholar 

  23. Lerner, T. N. et al. Intact-brain analyses reveal distinct information carried by SNc dopamine subcircuits. Cell 162, 635–647 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  24. Beier, K. T. et al. Circuit architecture of VTA dopamine neurons revealed by systematic input-output mapping. Cell 162, 622–634 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  25. Saunders, B. T., Richard, J. M., Margolis, E. B. & Janak, P. H. Dopamine neurons create Pavlovian conditioned stimuli with circuit-defined motivational properties. Nat. Neurosci. 21, 1072–1083 (2018). This study shows how VTA DA activation increases the value of an associated conditioned stimulus whereas SNc DA activation increases conditioned responding to the conditioned stimulus without increasing its value.

    CAS  PubMed  PubMed Central  Google Scholar 

  26. Poulin, J.-F. et al. Mapping projections of molecularly defined dopamine neuron subtypes using intersectional genetic approaches. Nat. Neurosci. 21, 1260–1271 (2018).

    CAS  PubMed  PubMed Central  Google Scholar 

  27. Montague, P. R., Dayan, P. & Sejnowski, T. J. A framework for mesencephalic dopamine systems based on predictive Hebbian learning. J. Neurosci. 16, 1936–1947 (1996).

    CAS  PubMed  Google Scholar 

  28. Schultz, W., Dayan, P. & Montague, P. R. A neural substrate of prediction and reward. Science 275, 1593–1599 (1997). This seminal paper connects DA activity with reinforcement learning models.

    CAS  PubMed  Google Scholar 

  29. Mirenowicz, J. & Schultz, W. Preferential activation of midbrain dopamine neurons by appetitive rather than aversive stimuli. Nature 379, 449–451 (1996).

    CAS  PubMed  Google Scholar 

  30. Hollerman, J. R. & Schultz, W. Dopamine neurons report an error in the temporal prediction of reward during learning. Nat. Neurosci. 1, 304–309 (1998).

    CAS  PubMed  Google Scholar 

  31. Schultz, W. Predictive reward signal of dopamine neurons. J. Neurophysiol. 80, 1–27 (1998).

    CAS  PubMed  Google Scholar 

  32. Fiorillo, C. D., Tobler, P. N. & Schultz, W. Discrete coding of reward probability and uncertainty by dopamine neurons. Science 299, 1898–1902 (2003).

    CAS  PubMed  Google Scholar 

  33. Roesch, M. R., Calu, D. J. & Schoenbaum, G. Dopamine neurons encode the better option in rats deciding between differently delayed or sized rewards. Nat. Neurosci. 10, 1615–1624 (2007).

    CAS  PubMed  PubMed Central  Google Scholar 

  34. Day, J. J., Roitman, M. F., Wightman, R. M. & Carelli, R. M. Associative learning mediates dynamic shifts in dopamine signaling in the nucleus accumbens. Nat. Neurosci. 10, 1020–1028 (2007).

    CAS  PubMed  Google Scholar 

  35. Bromberg-Martin, E. S., Matsumoto, M. & Hikosaka, O. Dopamine in motivational control: rewarding, aversive, and alerting. Neuron 68, 815–834 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  36. Cohen, J. Y., Haesler, S., Vong, L., Lowell, B. B. & Uchida, N. Neuron-type-specific signals for reward and punishment in the ventral tegmental area. Nature 482, 85–88 (2012). This study employs phototagging to confirm that VTA DA neurons represent RPE whereas VTA GABA neurons represent expected reward.

    CAS  PubMed  PubMed Central  Google Scholar 

  37. Eshel, N. et al. Arithmetic and local circuitry underlying dopamine prediction errors. Nature 525, 243–246 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  38. Reynolds, J. N. J., Hyland, B. I. & Wickens, J. R. A cellular mechanism of reward-related learning. Nature 413, 67–70 (2001).

    CAS  PubMed  Google Scholar 

  39. Reynolds, J. N. J. & Wickens, J. R. Dopamine-dependent plasticity of corticostriatal synapses. Neural Netw. 15, 507–521 (2002).

    PubMed  Google Scholar 

  40. Shen, W., Flajolet, M., Greengard, P. & Surmeier, D. J. Dichotomous dopaminergic control of striatal synaptic plasticity. Science 321, 848–851 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  41. Gerfen, C. R. & Surmeier, D. J. Modulation of striatal projection systems by dopamine. Annu. Rev. Neurosci. 34, 441–466 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  42. Bamford, N. S., Wightman, R. M. & Sulzer, D. Dopamine’s effects on corticostriatal synapses during reward-based behaviors. Neuron 97, 494–510 (2018). This recent review discusses mechanisms by which DA affects corticostriatal synapses and MSN activity during reward-seeking behaviours.

    CAS  PubMed  PubMed Central  Google Scholar 

  43. Olds, J. Self-stimulation of the brain; its use to study local effects of hunger, sex, and drugs. Science 127, 315–324 (1958).

    CAS  PubMed  Google Scholar 

  44. Corbett, D. & Wise, R. A. Intracranial self-stimulation in relation to the ascending dopaminergic systems of the midbrain: a moveable electrode mapping study. Brain Res. 185, 1–15 (1980).

    CAS  PubMed  Google Scholar 

  45. Fouriezos, G. & Wise, R. A. Pimozide-induced extinction of intracranial self-stimulation: response patterns rule out motor or performance deficits. Brain Res. 103, 377–380 (1976).

    CAS  PubMed  Google Scholar 

  46. Wise, R. A. Forebrain substrates of reward and motivation. J. Comp. Neurol. 493, 115–121 (2005).

    CAS  PubMed  PubMed Central  Google Scholar 

  47. Steinberg, E. E. et al. A causal link between prediction errors, dopamine neurons and learning. Nat. Neurosci. 16, 966–973 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  48. Sharpe, M. J. et al. Dopamine transients are sufficient and necessary for acquisition of model-based associations. Nat. Neurosci. 20, 735–742 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  49. Tsai, H.-C. et al. Phasic firing in dopaminergic neurons is sufficient for behavioral conditioning. Science 324, 1080–1084 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  50. Ilango, A. et al. Similar roles of substantia nigra and ventral tegmental dopamine neurons in reward and aversion. J. Neurosci. 34, 817–822 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  51. Witten, I. B. et al. Recombinase-driver rat lines: tools, techniques, and optogenetic application to dopamine-mediated reinforcement. Neuron 72, 721–733 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  52. Hamid, A. A. et al. Mesolimbic dopamine signals the value of work. Nat. Neurosci. 19, 117–126 (2016).

    CAS  PubMed  Google Scholar 

  53. Adamantidis, A. R. et al. Optogenetic interrogation of dopaminergic modulation of the multiple phases of reward-seeking behavior. J. Neurosci. 31, 10829–10835 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  54. Chang, C. Y. et al. Brief optogenetic inhibition of dopamine neurons mimics endogenous negative reward prediction errors. Nat. Neurosci. 19, 111–116 (2016).

    CAS  PubMed  Google Scholar 

  55. Parker, N. F. et al. Reward and choice encoding in terminals of midbrain dopamine neurons depends on striatal target. Nat. Neurosci. 19, 845–854 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  56. O’Doherty, J. et al. Dissociable roles of ventral and dorsal striatum in instrumental conditioning. Science 304, 452–454 (2004).

    PubMed  Google Scholar 

  57. Balleine, B. W., Delgado, M. R. & Hikosaka, O. The role of the dorsal striatum in reward and decision-making. J. Neurosci. 27, 8161–8165 (2007).

    CAS  PubMed  Google Scholar 

  58. Engelhard, B. et al. Specialized coding of sensory, motor and cognitive variables in VTA dopamine neurons. Nature https://doi.org/10.1038/s41586-019-1261-9 (2019).Cellular resolution imaging of VTA DA neurons reveals widespread reward representations multiplexed with specialized representations of task variables.

    CAS  PubMed  Google Scholar 

  59. Howe, M. W. & Dombeck, D. A. Rapid signalling in distinct dopaminergic axons during locomotion and reward. Nature 535, 505–510 (2016). Axonal imaging of DA terminals in the dorsal striatum reveals that distinct axons signal locomotion and reward.

    CAS  PubMed  PubMed Central  Google Scholar 

  60. Menegas, W., Akiti, K., Amo, R., Uchida, N. & Watabe-Uchida, M. Dopamine neurons projecting to the posterior striatum reinforce avoidance of threatening stimuli. Nat. Neurosci. 275, 1593 (2018). This paper shows that DA in the TS supports learning to avoid threatening stimuli whereas DA in the NAc supports learning to pursue rewarding stimuli.

    Google Scholar 

  61. Menegas, W., Babayan, B. M., Uchida, N. & Watabe-Uchida, M. Opposite initialization to novel cues in dopamine signaling in ventral and posterior striatum in mice. eLife 6, e21886 (2017).

    PubMed  PubMed Central  Google Scholar 

  62. Lee, R. S., Mattar, M. G., Parker, N. F., Witten, I. B. & Daw, N. D. Reward prediction error does not explain movement selectivity in DMS-projecting dopamine neurons. eLife 8, e42992 (2019).

    PubMed  PubMed Central  Google Scholar 

  63. da Silva, J. A., Tecuapetla, F., Paixão, V. & Costa, R. M. Dopamine neuron activity before action initiation gates and invigorates future movements. Nature 554, 244–248 (2018).

    PubMed  Google Scholar 

  64. Barter, J. W. et al. Beyond reward prediction errors: the role of dopamine in movement kinematics. Front. Integr. Neurosci. 9, 39 (2015).

    PubMed  PubMed Central  Google Scholar 

  65. Joshua, M., Adler, A., Mitelman, R., Vaadia, E. & Bergman, H. Midbrain dopaminergic neurons and striatal cholinergic interneurons encode the difference between reward and aversive events at different epochs of probabilistic classical conditioning trials. J. Neurosci. 28, 11673–11684 (2008).

    CAS  PubMed  Google Scholar 

  66. Matsumoto, M. & Hikosaka, O. Two types of dopamine neuron distinctly convey positive and negative motivational signals. Nature 459, 837–841 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  67. Brischoux, F., Chakraborty, S., Brierley, D. I. & Ungless, M. A. Phasic excitation of dopamine neurons in ventral VTA by noxious stimuli. Proc. Natl Acad. Sci. USA 106, 4894–4899 (2009).

    CAS  PubMed  Google Scholar 

  68. Gangarossa, G. et al. Spatial distribution of D1R- and D2R-expressing medium-sized spiny neurons differs along the rostro-caudal axis of the mouse dorsal striatum. Front. Neural Circuits 7, 124 (2013).

    PubMed  PubMed Central  Google Scholar 

  69. Hikosaka, O., Takikawa, Y. & Kawagoe, R. Role of the basal ganglia in the control of purposive saccadic eye movements. Physiol. Rev. 80, 953–978 (2000).

    CAS  PubMed  Google Scholar 

  70. Calabresi, P., Picconi, B., Tozzi, A., Ghiglieri, V. & Di Filippo, M. Direct and indirect pathways of basal ganglia: a critical reappraisal. Nat. Neurosci. 17, 1022–1030 (2014).

    CAS  PubMed  Google Scholar 

  71. Oldenburg, I. A. & Sabatini, B. L. Antagonistic but not symmetric regulation of primary motor cortex by basal ganglia direct and indirect pathways. Neuron 86, 1174–1181 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  72. Roseberry, T. K. et al. Cell-type-specific control of brainstem locomotor circuits by basal ganglia. Cell 164, 526–537 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  73. Lauwereyns, J., Watanabe, K., Coe, B. & Hikosaka, O. A neural correlate of response bias in monkey caudate nucleus. Nature 418, 413–417 (2002).

    CAS  PubMed  Google Scholar 

  74. Samejima, K., Ueda, Y., Doya, K. & Kimura, M. Representation of action-specific reward values in the striatum. Science 310, 1337–1340 (2005).

    CAS  PubMed  Google Scholar 

  75. Lau, B. & Glimcher, P. W. Value representations in the primate striatum during matching behavior. Neuron 58, 451–463 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  76. Ding, L. & Gold, J. I. Caudate encodes multiple computations for perceptual decisions. J. Neurosci. 30, 15747–15759 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  77. Gong, S. et al. Targeting Cre recombinase to specific neuron populations with bacterial artificial chromosome constructs. J. Neurosci. 27, 9817–9823 (2007).

    CAS  PubMed  Google Scholar 

  78. Gerfen, C. R., Paletzki, R. & Heintz, N. GENSAT BAC cre-recombinase driver lines to study the functional organization of cerebral cortical and basal ganglia circuits. Neuron 80, 1368–1383 (2013).

    CAS  PubMed  Google Scholar 

  79. Cui, G. et al. Concurrent activation of striatal direct and indirect pathways during action initiation. Nature 494, 238–242 (2013). This study is the first to show that D1R and D2R MSNs are co-activated during movement and inactive during immobility, contrary to some theories of striatal function.

    CAS  PubMed  PubMed Central  Google Scholar 

  80. Barbera, G. et al. Spatially compact neural clusters in the dorsal striatum encode locomotion relevant information. Neuron 92, 202–213 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  81. Klaus, A. et al. The spatiotemporal organization of the striatum encodes action space. Neuron 96, 949 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  82. Markowitz, J. E. et al. The striatum organizes 3D behavior via moment-to-moment action selection. Cell 174, 44–58 (2018). This study uses machine learning algorithms to characterize spontaneous behaviour into discrete, subsecond components and describes D1R and D2R MSN responses to the identity and sequence of these behavioural components.

    CAS  PubMed  PubMed Central  Google Scholar 

  83. Parker, J. G. et al. Diametric neural ensemble dynamics in parkinsonian and dyskinetic states. Nature 557, 177–182 (2018). This study thoroughly probes the effects of DA depletion and subsequent administration of dopaminergic agonists and antagonists on the activity of D1R-expressing and D2R-expressing MSNs in vivo.

    CAS  PubMed  PubMed Central  Google Scholar 

  84. Meng, C. et al. Spectrally resolved fiber photometry for multi-component analysis of brain circuits. Neuron 98, 707–717 (2018).

    CAS  PubMed  PubMed Central  Google Scholar 

  85. London, T. D. et al. Coordinated ramping of dorsal striatal pathways preceding food approach and consumption. J. Neurosci. 38, 3547–3558 (2018).

    CAS  PubMed  PubMed Central  Google Scholar 

  86. Isomura, Y. et al. Reward-modulated motor information in identified striatum neurons. J. Neurosci. 33, 10209–10220 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  87. Jin, X., Tecuapetla, F. & Costa, R. M. Basal ganglia subcircuits distinctively encode the parsing and concatenation of action sequences. Nat. Neurosci. 17, 423–430 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  88. Sippy, T., Lapray, D., Crochet, S. & Petersen, C. C. H. Cell-type-specific sensorimotor processing in striatal projection neurons during goal-directed behavior. Neuron 88, 298–305 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  89. Geddes, C. E., Li, H. & Jin, X. Optogenetic editing reveals the hierarchical organization of learned action sequences. Cell 174, 32–43 (2018).

    CAS  PubMed  PubMed Central  Google Scholar 

  90. Nonomura, S. et al. Monitoring and updating of action selection for goal-directed behavior through the striatal direct and indirect pathways. Neuron 99, 1302–1314 (2018).

    CAS  PubMed  Google Scholar 

  91. Donahue, C. H., Liu, M. & Kreitzer, A. Distinct value encoding in striatal direct and indirect pathways during adaptive learning. Preprint at bioRxiv https://doi.org/10.1101/277855 (2018).

    Article  Google Scholar 

  92. Tecuapetla, F., Matias, S., Dugue, G. P., Mainen, Z. F. & Costa, R. M. Balanced activity in basal ganglia projection pathways is critical for contraversive movements. Nat. Commun. 5, 4315 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  93. Cazorla, M. et al. Dopamine D2 receptors regulate the anatomical and functional balance of basal ganglia circuitry. Neuron 81, 153–164 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  94. Collins, A. G. E. & Frank, M. J. Opponent actor learning (OpAL): modeling interactive effects of striatal dopamine on reinforcement learning and choice incentive. Psychol. Rev. 121, 337–366 (2014).

    PubMed  Google Scholar 

  95. Bariselli, S., Fobbs, W. C., Creed, M. C. & Kravitz, A. V. A competitive model for striatal action selection. Brain Res. 1713, 70–79 (2018).

    PubMed  Google Scholar 

  96. Frank, M. J., Seeberger, L. C. & O’reilly, R. C. By carrot or by stick: cognitive reinforcement learning in parkinsonism. Science 306, 1940–1943 (2004).

    CAS  PubMed  Google Scholar 

  97. Peak, J., Hart, G. & Balleine, B. W. From learning to action: the integration of dorsal striatal input and output pathways in instrumental conditioning. Eur. J. Neurosci. 49, 658–671 (2019).

    PubMed  Google Scholar 

  98. Yartsev, M. M., Hanks, T. D., Yoon, A. M. & Brody, C. D. Causal contribution and dynamical encoding in the striatum during evidence accumulation. eLife 7, e34929 (2018).

    PubMed  PubMed Central  Google Scholar 

  99. Shin, J. H., Kim, D. & Jung, M. W. Differential coding of reward and movement information in the dorsomedial striatal direct and indirect pathways. Nat. Commun. 9, 404 (2018).

    PubMed  PubMed Central  Google Scholar 

  100. Zalocusky, K. A. et al. Nucleus accumbens D2R cells signal prior outcomes and control risky decision-making. Nature 531, 642–646 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  101. Lau, B. & Glimcher, P. W. Dynamic response-by-response models of matching behavior in rhesus monkeys. J. Exp. Anal. Behav. 84, 555–579 (2005).

    PubMed  PubMed Central  Google Scholar 

  102. Tai, L.-H., Lee, A. M., Benavidez, N., Bonci, A. & Wilbrecht, L. Transient stimulation of distinct subpopulations of striatal neurons mimics changes in action value. Nat. Neurosci. 15, 1281–1289 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  103. Kravitz, A. V., Tye, L. D. & Kreitzer, A. C. Distinct roles for direct and indirect pathway striatal neurons in reinforcement. Nat. Neurosci. 15, 816–818 (2012). This paper shows how D1R and D2R MSN activity in DMS is sufficient to positively and negatively reinforce intracranial self-stimulation, respectively, but this learning does not depend on DA transmission.

    CAS  PubMed  PubMed Central  Google Scholar 

  104. Yttri, E. A. & Dudman, J. T. Opponent and bidirectional control of movement velocity in the basal ganglia. Nature 533, 402–406 (2016). This study shows that D1R and D2R MSN activity in DMS is sufficient to positively and negatively reinforce movement velocity, respectively, and this learning depends on DA transmission.

    CAS  PubMed  PubMed Central  Google Scholar 

  105. Lobo, M. K. et al. Cell type-specific loss of BDNF signaling mimics optogenetic control of cocaine reward. Science 330, 385–390 (2010). D1R and D2R MSN activity in NAc enhances or suppresses, respectively, the establishment of a cocaine CPP.

    CAS  PubMed  PubMed Central  Google Scholar 

  106. Wang, L., Rangarajan, K. V., Gerfen, C. R. & Krauzlis, R. J. Activation of striatal neurons causes a perceptual decision bias during visual change detection in mice. Neuron 98, 669 (2018).

    CAS  PubMed  Google Scholar 

  107. Tecuapetla, F., Jin, X., Lima, S. Q. & Costa, R. M. Complementary contributions of striatal projection pathways to action initiation and execution. Cell 166, 703–715 (2016).

    CAS  PubMed  Google Scholar 

  108. Vicente, A. M., Galvão-Ferreira, P., Tecuapetla, F. & Costa, R. M. Direct and indirect dorsolateral striatum pathways reinforce different action strategies. Curr. Biol. 26, R267–269 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  109. Cole, S. L., Robinson, M. J. F. & Berridge, K. C. Optogenetic self-stimulation in the nucleus accumbens: D1 reward versus D2 ambivalence. PLOS ONE 13, e0207694 (2018).

    PubMed  PubMed Central  Google Scholar 

  110. Soares-Cunha, C. et al. Activation of D2 dopamine receptor-expressing neurons in the nucleus accumbens increases motivation. Nat. Commun. 7, 11829 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  111. Carvalho Poyraz, F. et al. Decreasing striatopallidal pathway function enhances motivation by energizing the initiation of goal-directed action. J. Neurosci. 36, 5988–6001 (2016).

    PubMed  PubMed Central  Google Scholar 

  112. Gallo, E. F. et al. Accumbens dopamine D2 receptors increase motivation by decreasing inhibitory transmission to the ventral pallidum. Nat. Commun. 9, 1086 (2018).

    PubMed  PubMed Central  Google Scholar 

  113. Apicella, P. The role of the intrinsic cholinergic system of the striatum: what have we learned from TAN recordings in behaving animals? Neuroscience 360, 81–94 (2017).

    CAS  PubMed  Google Scholar 

  114. Hasselmo, M. E. The role of acetylcholine in learning and memory. Curr. Opin. Neurobiol. 16, 710–715 (2006).

    CAS  PubMed  PubMed Central  Google Scholar 

  115. Macintosh, F. C. The distribution of acetylcholine in the peripheral and the central nervous system. J. Physiol. 99, 436–442 (1941).

    CAS  PubMed  PubMed Central  Google Scholar 

  116. Hebb, C. O. & Silver, A. Gradient of cholinesterase activity and of choline acetylase activity in nerve fibres: gradient of choline acetylase activity. Nature 189, 123–125 (1961).

    CAS  PubMed  Google Scholar 

  117. Lim, S. A. O., Kang, U. J. & McGehee, D. S. Striatal cholinergic interneuron regulation and circuit effects. Front. Synaptic Neurosci. 6, 22 (2014).

    PubMed  PubMed Central  Google Scholar 

  118. Wilson, C. J., Chang, H. T. & Kitai, S. T. Firing patterns and synaptic potentials of identified giant aspiny interneurons in the rat neostriatum. J. Neurosci. 10, 508–519 (1990).

    CAS  PubMed  Google Scholar 

  119. Inokawa, H., Yamada, H., Matsumoto, N., Muranishi, M. & Kimura, M. Juxtacellular labeling of tonically active neurons and phasically active neurons in the rat striatum. Neuroscience 168, 395–404 (2010).

    CAS  PubMed  Google Scholar 

  120. Schulz, J. M., Oswald, M. J. & Reynolds, J. N. J. Visual-induced excitation leads to firing pauses in striatal cholinergic interneurons. J. Neurosci. 31, 11133–11143 (2011).

    CAS  PubMed  Google Scholar 

  121. Kimura, M., Rajkowski, J. & Evarts, E. Tonically discharging putamen neurons exhibit set-dependent responses. Proc. Natl Acad. Sci. USA 81, 4998–5001 (1984).

    CAS  PubMed  Google Scholar 

  122. Aosaki, T. et al. Responses of tonically active neurons in the primate’s striatum undergo systematic changes during behavioral sensorimotor conditioning. J. Neurosci. 14, 3969–3984 (1994).

    CAS  PubMed  Google Scholar 

  123. Graybiel, A. M., Aosaki, T., Flaherty, A. W. & Kimura, M. The basal ganglia and adaptive motor control. Science 265, 1826–1831 (1994).

    CAS  PubMed  Google Scholar 

  124. Aosaki, T., Graybiel, A. M. & Kimura, M. Effect of the nigrostriatal dopamine system on acquired neural responses in the striatum of behaving monkeys. Science 265, 412–415 (1994).

    CAS  PubMed  Google Scholar 

  125. Ravel, S., Legallet, E. & Apicella, P. Tonically active neurons in the monkey striatum do not preferentially respond to appetitive stimuli. Exp. Brain Res. 128, 531–534 (1999).

    CAS  PubMed  Google Scholar 

  126. Goldberg, J. A. & Reynolds, J. N. J. Spontaneous firing and evoked pauses in the tonically active cholinergic interneurons of the striatum. Neuroscience 198, 27–43 (2011).

    CAS  PubMed  Google Scholar 

  127. Witten, I. B. et al. Cholinergic interneurons control local circuit activity and cocaine conditioning. Science 330, 1677–1681 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  128. Lee, J., Finkelstein, J., Choi, J. Y. & Witten, I. B. Linking cholinergic interneurons, synaptic plasticity, and behavior during the extinction of a cocaine-context association. Neuron 90, 1071–1085 (2016). This study shows that CINs regulate glutamatergic synaptic plasticity in the NAc during cocaine context extinction in a manner that can explain the associated behavioural changes.

    CAS  PubMed  PubMed Central  Google Scholar 

  129. Bradfield, L. A., Bertran-Gonzalez, J., Chieng, B. & Balleine, B. W. The thalamostriatal pathway and cholinergic control of goal-directed action: interlacing new with existing learning in the striatum. Neuron 79, 153–166 (2013).

    CAS  PubMed  Google Scholar 

  130. Aoki, S., Liu, A. W., Zucca, A., Zucca, S. & Wickens, J. R. Role of striatal cholinergic interneurons in set-shifting in the rat. J. Neurosci. 35, 9424–9431 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  131. Okada, K. et al. Enhanced flexibility of place discrimination learning by targeting striatal cholinergic interneurons. Nat. Commun. 5, 3778 (2014).

    CAS  PubMed  Google Scholar 

  132. Matamales, M. et al. Aging-related dysfunction of striatal cholinergic interneurons produces conflict in action selection. Neuron 90, 362–373 (2016).

    CAS  PubMed  Google Scholar 

  133. Collins, A. L. et al. Nucleus accumbens cholinergic interneurons oppose cue-motivated behavior. Biol. Psychiatry https://doi.org/10.1016/j.biopsych.2019.02.014 (2019).

    Article  Google Scholar 

  134. English, D. F. et al. GABAergic circuits mediate the reinforcement-related signals of striatal cholinergic interneurons. Nat. Neurosci. 15, 123–130 (2011).

    PubMed  PubMed Central  Google Scholar 

  135. Nelson, A. B. et al. Striatal cholinergic interneurons drive GABA release from dopamine terminals. Neuron 82, 63–70 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  136. Tritsch, N. X., Oh, W.-J., Gu, C. & Sabatini, B. L. Midbrain dopamine neurons sustain inhibitory transmission using plasma membrane uptake of GABA, not synthesis. eLife 3, e01936 (2014).

    PubMed  PubMed Central  Google Scholar 

  137. Cachope, R. et al. Selective activation of cholinergic interneurons enhances accumbal phasic dopamine release: setting the tone for reward processing. Cell Rep. 2, 33–41 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  138. Threlfell, S. et al. Striatal dopamine release is triggered by synchronized activity in cholinergic interneurons. Neuron 75, 58–64 (2012).

    CAS  PubMed  Google Scholar 

  139. Selemon, L. D. & Goldman-Rakic, P. S. Longitudinal topography and interdigitation of corticostriatal projections in the rhesus monkey. J. Neurosci. 5, 776–794 (1985).

    CAS  PubMed  Google Scholar 

  140. Groenewegen, H. J., Berendse, H. W., Wolters, J. G. & Lohman, A. H. The anatomical relationship of the prefrontal cortex with the striatopallidal system, the thalamus and the amygdala: evidence for a parallel organization. Prog. Brain Res. 85, 95–116 (1990).

    CAS  PubMed  Google Scholar 

  141. Flaherty, A. W. & Graybiel, A. M. Corticostriatal transformations in the primate somatosensory system. Projections from physiologically mapped body-part representations. J. Neurophysiol. 66, 1249–1263 (1991).

    CAS  PubMed  Google Scholar 

  142. Berendse, H. W., Galis-de Graaf, Y. & Groenewegen, H. J. Topographical organization and relationship with ventral striatal compartments of prefrontal corticostriatal projections in the rat. J. Comp. Neurol. 316, 314–347 (1992).

    CAS  PubMed  Google Scholar 

  143. Pan, W. X., Mao, T. & Dudman, J. T. Inputs to the dorsal striatum of the mouse reflect the parallel circuit architecture of the forebrain. Front. Neuroanat. 4, 147 (2010).

    PubMed  PubMed Central  Google Scholar 

  144. Wall, N. R., De La Parra, M., Callaway, E. M. & Kreitzer, A. C. Differential innervation of direct- and indirect-pathway striatal projection neurons. Neuron 79, 347–360 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  145. Guo, Q. et al. Whole-brain mapping of inputs to projection neurons and cholinergic interneurons in the dorsal striatum. PLOS ONE 10, e0123381 (2015).

    PubMed  PubMed Central  Google Scholar 

  146. Heilbronner, S. R., Rodriguez-Romaguera, J., Quirk, G. J., Groenewegen, H. J. & Haber, S. N. Circuit-based corticostriatal homologies between rat and primate. Biol. Psychiatry 80, 509–521 (2016).

    PubMed  PubMed Central  Google Scholar 

  147. Hunnicutt, B. J. et al. A comprehensive excitatory input map of the striatum reveals novel functional organization. eLife 5, e19103 (2016).

    PubMed  PubMed Central  Google Scholar 

  148. Hintiryan, H. et al. The mouse cortico-striatal projectome. Nat. Neurosci. 19, 1100–1114 (2016). This paper and that of Hunnicutt et al. (2016) provide detailed cortical and thalamic input maps to the striatum and use clustering methods on the anatomical distribution of these inputs to identify striatal subdomains.

    CAS  PubMed  PubMed Central  Google Scholar 

  149. Stuber, G. D. et al. Excitatory transmission from the amygdala to nucleus accumbens facilitates reward seeking. Nature 475, 377–380 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  150. Britt, J. P. et al. Synaptic and behavioral profile of multiple glutamatergic inputs to the nucleus accumbens. Neuron 76, 790–803 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  151. Koralek, A. C., Jin, X., Long, J. D. 2nd, Costa, R. M. & Carmena, J. M. Corticostriatal plasticity is necessary for learning intentional neuroprosthetic skills. Nature 483, 331–335 (2012). This study shows that corticostriatal plasticity is required for learning neuroprosthetic control of motor cortex neurons, irrespective of movement, and that the activity of striatal neurons is modulated by this type of goal-directed learning.

    CAS  PubMed  PubMed Central  Google Scholar 

  152. Znamenskiy, P. & Zador, A. M. Corticostriatal neurons in auditory cortex drive decisions during auditory discrimination. Nature 497, 482–485 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  153. MacAskill, A. F., Cassel, J. M. & Carter, A. G. Cocaine exposure reorganizes cell type- and input-specific connectivity in the nucleus accumbens. Nat. Neurosci. 17, 1198–1207 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  154. Pascoli, V. et al. Contrasting forms of cocaine-evoked plasticity control components of relapse. Nature 509, 459–464 (2014).

    CAS  PubMed  Google Scholar 

  155. Friedman, A. et al. A corticostriatal path targeting striosomes controls decision-making under conflict. Cell 161, 1320–1333 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  156. Rothwell, P. E. et al. Input- and output-specific regulation of serial order performance by corticostriatal circuits. Neuron 88, 345–356 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  157. Namburi, P. et al. A circuit mechanism for differentiating positive and negative associations. Nature 520, 675–678 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  158. Xiong, Q., Znamenskiy, P. & Zador, A. M. Selective corticostriatal plasticity during acquisition of an auditory discrimination task. Nature 521, 348–351 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  159. Christoffel, D. J. et al. Excitatory transmission at thalamo-striatal synapses mediates susceptibility to social stress. Nat. Neurosci. 18, 962–964 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  160. Zhu, Y., Wienecke, C. F. R., Nachtrab, G. & Chen, X. A thalamic input to the nucleus accumbens mediates opiate dependence. Nature 530, 219–222 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  161. Okuyama, T., Kitamura, T., Roy, D. S., Itohara, S. & Tonegawa, S. Ventral CA1 neurons store social memory. Science 353, 1536–1541 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  162. Yoo, J. H. et al. Ventral tegmental area glutamate neurons co-release GABA and promote positive reinforcement. Nat. Commun. 7, 13697 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  163. Beyeler, A. et al. Divergent routing of positive and negative information from the amygdala during memory retrieval. Neuron 90, 348–361 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  164. Otis, J. M. et al. Prefrontal cortex output circuits guide reward seeking through divergent cue encoding. Nature 543, 103–107 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  165. Murugan, M. et al. Combined social and spatial coding in a descending projection from the prefrontal cortex. Cell 171, 1663–1677 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  166. Kupferschmidt, D. A., Juczewski, K., Cui, G., Johnson, K. A. & Lovinger, D. M. Parallel, but dissociable, processing in discrete corticostriatal inputs encodes skill learning. Neuron 96, 476–489 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  167. Friedman, A. et al. Chronic stress alters striosome-circuit dynamics, leading to aberrant decision-making. Cell 171, 1191–1205 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  168. Kim, C. K. et al. Molecular and circuit-dynamical identification of top-down neural mechanisms for restraint of reward seeking. Cell 170, 1013–1027 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  169. Amadei, E. A. et al. Dynamic corticostriatal activity biases social bonding in monogamous female prairie voles. Nature 546, 297–301 (2017). This paper demonstrates that pair bonding in prairie voles modulates the projection from the mPFC to the NAc and that stimulation of this projection increases preference for a social target.

    CAS  PubMed  PubMed Central  Google Scholar 

  170. Sweis, B. M., Larson, E. B., Redish, A. D. & Thomas, M. J. Altering gain of the infralimbic-to-accumbens shell circuit alters economically dissociable decision-making algorithms. Proc. Natl Acad. Sci. USA 115, E6347–E6355 (2018).

    CAS  PubMed  Google Scholar 

  171. Cui, Q., Li, Q., Geng, H., Chen, L. & Ip, N. Y. Dopamine receptors mediate strategy abandoning via modulation of a specific prelimbic cortex–nucleus accumbens pathway in mice. Proc. Natl Acad. Sci. USA 115, E4890–E4899 (2018).

    CAS  PubMed  Google Scholar 

  172. Díaz-Hernández, E. et al. The thalamostriatal projections contribute to the initiation and execution of a sequence of movements. Neuron 100, 739–752 (2018).

    PubMed  Google Scholar 

  173. LeGates, T. A. et al. Reward behaviour is regulated by the strength of hippocampus-nucleus accumbens synapses. Nature 564, 258–262 (2018).

    CAS  PubMed  PubMed Central  Google Scholar 

  174. Hart, G., Bradfield, L. A., Fok, S. Y., Chieng, B. & Balleine, B. W. The bilateral prefronto-striatal pathway is necessary for learning new goal-directed actions. Curr. Biol. 28, 2218–2229 (2018).

    CAS  PubMed  Google Scholar 

  175. Trouche, S. et al. A hippocampus-accumbens tripartite neuronal motif guides appetitive memory in space. Cell 176, 1393–1406 (2019).

    CAS  PubMed  PubMed Central  Google Scholar 

  176. Chen, L., Wang, X., Ge, S. & Xiong, Q. Medial geniculate body and primary auditory cortex differentially contribute to striatal sound representations. Nat. Commun. 10, 418 (2019).

    PubMed  PubMed Central  Google Scholar 

  177. Yamamoto, S., Monosov, I. E., Yasuda, M. & Hikosaka, O. What and where information in the caudate tail guides saccades to visual objects. J. Neurosci. 32, 11005–11016 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  178. Yamamoto, S., Kim, H. F. & Hikosaka, O. Reward value-contingent changes of visual responses in the primate caudate tail associated with a visuomotor skill. J. Neurosci. 33, 11227–11238 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  179. Kim, H. F. & Hikosaka, O. Distinct basal ganglia circuits controlling behaviors guided by flexible and stable values. Neuron 79, 1001–1010 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  180. Kim, H. F., Amita, H. & Hikosaka, O. Indirect pathway of caudal basal ganglia for rejection of valueless visual objects. Neuron 94, 920–930 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  181. Surmeier, D. J., Ding, J., Day, M., Wang, Z. & Shen, W. D1 and D2 dopamine-receptor modulation of striatal glutamatergic signaling in striatal medium spiny neurons. Trends Neurosci. 30, 228–235 (2007).

    CAS  PubMed  Google Scholar 

  182. Pawlak, V. & Kerr, J. N. D. Dopamine receptor activation is required for corticostriatal spike-timing-dependent plasticity. J. Neurosci. 28, 2435–2446 (2008).

    CAS  PubMed  Google Scholar 

  183. Kravitz, A. V. et al. Regulation of parkinsonian motor behaviours by optogenetic control of basal ganglia circuitry. Nature 466, 622–626 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  184. Bartholomew, R. A. et al. Striatonigral control of movement velocity in mice. Eur. J. Neurosci. 43, 1097–1110 (2016).

    PubMed  Google Scholar 

  185. Brown, M. T. C. et al. Ventral tegmental area GABA projections pause accumbal cholinergic interneurons to enhance associative learning. Nature 492, 452–456 (2012).

    CAS  PubMed  Google Scholar 

  186. Kawai, R. et al. Motor cortex is required for learning but not for executing a motor skill. Neuron 86, 800–812 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  187. Graybiel, A. M. Habits, rituals, and the evaluative brain. Annu. Rev. Neurosci. 31, 359–387 (2008).

    CAS  PubMed  Google Scholar 

  188. Liljeholm, M. & O’Doherty, J. P. Contributions of the striatum to learning, motivation, and performance: an associative account. Trends Cogn. Sci. 16, 467–475 (2012).

    PubMed  PubMed Central  Google Scholar 

  189. Gruber, A. J. & McDonald, R. J. Context, emotion, and the strategic pursuit of goals: interactions among multiple brain systems controlling motivated behavior. Front. Behav. Neurosci. 6, 50 (2012).

    PubMed  PubMed Central  Google Scholar 

  190. Balleine, B. W. & O’Doherty, J. P. Human and rodent homologies in action control: corticostriatal determinants of goal-directed and habitual action. Neuropsychopharmacology 35, 48–69 (2010). This paper reviews human and rodent studies investigating striatal involvement in goal-directed and habitual behaviour.

    PubMed  Google Scholar 

  191. Yin, H. H. & Knowlton, B. J. The role of the basal ganglia in habit formation. Nat. Rev. Neurosci. 7, 464–476 (2006).

    CAS  PubMed  Google Scholar 

  192. Barnes, T. D., Kubota, Y., Hu, D., Jin, D. Z. & Graybiel, A. M. Activity of striatal neurons reflects dynamic encoding and recoding of procedural memories. Nature 437, 1158–1161 (2005).

    CAS  PubMed  Google Scholar 

  193. Yin, H. H. et al. Dynamic reorganization of striatal circuits during the acquisition and consolidation of a skill. Nat. Neurosci. 12, 333–341 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  194. Thorn, C. A., Atallah, H., Howe, M. & Graybiel, A. M. Differential dynamics of activity changes in dorsolateral and dorsomedial striatal loops during learning. Neuron 66, 781–795 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  195. Dolan, R. J. & Dayan, P. Goals and habits in the brain. Neuron 80, 312–325 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  196. O’Hare, J. K. et al. Pathway-specific striatal substrates for habitual behavior. Neuron 89, 472–479 (2016). This paper shows correlations between performance of habitual behaviour and the strengthening of cortically evoked activity in D1R and D2R MSNs in the DLS as well as changes in the relative timing of activation of the two pathways.

    PubMed  PubMed Central  Google Scholar 

  197. Yin, H. H., Ostlund, S. B., Knowlton, B. J. & Balleine, B. W. The role of the dorsomedial striatum in instrumental conditioning. Eur. J. Neurosci. 22, 513–523 (2005).

    PubMed  Google Scholar 

  198. Setlow, B., Schoenbaum, G. & Gallagher, M. Neural encoding in ventral striatum during olfactory discrimination learning. Neuron 38, 625–636 (2003).

    CAS  PubMed  Google Scholar 

  199. Roitman, M. F., Wheeler, R. A. & Carelli, R. M. Nucleus accumbens neurons are innately tuned for rewarding and aversive taste stimuli, encode their predictors, and are linked to motor output. Neuron 45, 587–597 (2005).

    CAS  PubMed  Google Scholar 

  200. Groenewegen, H. J., Wright, C. I., Beijer, A. V. & Voorn, P. Convergence and segregation of ventral striatal inputs and outputs. Ann. NY Acad. Sci. 877, 49–63 (1999).

    CAS  PubMed  Google Scholar 

  201. Watabe-Uchida, M., Zhu, L., Ogawa, S. K., Vamanrao, A. & Uchida, N. Whole-brain mapping of direct inputs to midbrain dopamine neurons. Neuron 74, 858–873 (2012).

    CAS  PubMed  Google Scholar 

  202. Mannella, F., Gurney, K. & Baldassarre, G. The nucleus accumbens as a nexus between values and goals in goal-directed behavior: a review and a new hypothesis. Front. Behav. Neurosci. 7, 135 (2013).

    PubMed  PubMed Central  Google Scholar 

  203. Menegas, W. et al. Dopamine neurons projecting to the posterior striatum form an anatomically distinct subclass. eLife 4, e10032 (2015).

    PubMed  PubMed Central  Google Scholar 

  204. Howe, M. W., Tierney, P. L., Sandberg, S. G., Phillips, P. E. M. & Graybiel, A. M. Prolonged dopamine signalling in striatum signals proximity and value of distant rewards. Nature 500, 575–579 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  205. Freeze, B. S., Kravitz, A. V., Hammack, N., Berke, J. D. & Kreitzer, A. C. Control of basal ganglia output by direct and indirect pathway projection neurons. J. Neurosci. 33, 18531–18539 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  206. Kim, K. M. et al. Optogenetic mimicry of the transient activation of dopamine neurons by natural reward is sufficient for operant reinforcement. PLOS ONE 7, e33612 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

The authors thank L. Pinto for comments on this manuscript and W. Fleming for providing a figure schematic. This work was funded by New York Stem Cell Foundation (NYSCF), Pew, McKnight, NARSAD (US National Alliance for Research on Schizophrenia and Depression) and Sloan Foundation grants to I.B.W.; US National Institutes of Health (NIH) grants U19 NS104648-01, DP2 DA035149-01 and 5R01MH106689-02 (to I.B.W.) and F32 MH112320-02 (to J.C.); and Army Research Office grant W911NF-17-1-0554. I.B.W. is an NYSCF–Robertson Investigator.

Reviewer information

Nature Reviews Neuroscience thanks D. Sulzer and the other, anonymous reviewers for their contribution to the peer review of this work.

Author information

Authors and Affiliations

Authors

Contributions

Both authors researched data for the article, made substantial contributions to the discussion of content, wrote the manuscript and reviewed or edited the manuscript before submission.

Corresponding author

Correspondence to Ilana B. Witten.

Ethics declarations

Competing interests

The authors declare no competing interests.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Glossary

Basal ganglia

An evolutionarily conserved group of interconnected subcortical nuclei that are involved in motor, cognitive and limbic processes.

Reinforcement learning

A learning process in which performance of a behaviour is modified by positive or negative feedback.

Medial forebrain bundle

A white-matter tract that contains dopaminergic axons travelling from the ventral tegmental area and substantia nigra pars compacta to the striatum.

Stimulus–outcome associations

Associations between sensory stimuli and the outcomes they predict, which induce conditioned behaviours, although experience of the outcome is independent of that behaviour.

Stimulus–response associations

Associations that result in the performance of actions in response to sensory stimuli, regardless of the value of the outcomes of the actions.

Action–outcome associations

Associations between actions (or responses) and the outcomes of those actions, the performance of which depends on the value of the outcomes.

Probabilistic reversal learning task

A behavioural task in which participants learn associations between actions and reward probabilities that are then reversed, requiring updating of learned associations.

Conditioned place preference

(CPP). An assay for measuring context-reward associations that evaluates how much time animals spend in a spatial location associated with a particular stimulus.

Devaluation test

A measurement of performance of an action with a learned outcome that becomes devalued (for example, with satiety) to assess whether a behaviour is more goal-directed or habitual.

Cost–benefit comparison

A comparison between actions that are associated with both a benefit (such as reward) and a cost (such as punishment).

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Cox, J., Witten, I.B. Striatal circuits for reward learning and decision-making. Nat Rev Neurosci 20, 482–494 (2019). https://doi.org/10.1038/s41583-019-0189-2

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41583-019-0189-2

This article is cited by

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing