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Dichotomous regulation of striatal plasticity by dynorphin

Abstract

Modulation of corticostriatal plasticity alters the information flow throughout basal ganglia circuits and represents a fundamental mechanism for motor learning, action selection, and reward. Synaptic plasticity in the striatal direct- and indirect-pathway spiny projection neurons (dSPNs and iSPNs) is regulated by two distinct networks of GPCR signaling cascades. While it is well-known that dopamine D2 and adenosine A2a receptors bi-directionally regulate iSPN plasticity, it remains unclear how D1 signaling modulation of synaptic plasticity is counteracted by dSPN-specific Gi signaling. Here, we show that striatal dynorphin selectively suppresses long-term potentiation (LTP) through Kappa Opioid Receptor (KOR) signaling in dSPNs. Both KOR antagonism and conditional deletion of dynorphin in dSPNs enhance LTP counterbalancing with different levels of D1 receptor activation. Behaviorally, mice lacking dynorphin in D1 neurons show comparable motor behavior and reward-based learning, but enhanced flexibility during reversal learning. These findings support a model in which D1R and KOR signaling bi-directionally modulate synaptic plasticity and behavior in the direct pathway.

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Fig. 1: Pathway-specific modulation of striatal STDP-LTP by KOR.
Fig. 2: Direct pathway-specific deletion of pDyn.
Fig. 3: D1-pDyn cKO enhanced LTP in dSPNs, but not iSPNs.
Fig. 4: D1R signaling modulated the effect of dyn/KOR on dSPN LTP.
Fig. 5: Behavioral assessment of pDyn WT and cKO mice.
Fig. 6: Enhanced reversal learning in pDyn cKO mice in 4-choice odor discrimination task.

References

  1. Graybiel AM, Grafton ST. The striatum: where skills and habits meet. Cold Spring Harb Perspect Biol. 2015;7:a021691.

    Google Scholar 

  2. Gremel CM, Costa RM. Orbitofrontal and striatal circuits dynamically encode the shift between goal-directed and habitual actions. Nat Commun. 2013;4:2264.

    Google Scholar 

  3. Kauer JA, Malenka RC. Synaptic plasticity and addiction. Nat Rev Neurosci. 2007;8:844–58.

    CAS  Google Scholar 

  4. Surmeier DJ, Graves SM, Shen W. Dopaminergic modulation of striatal networks in health and Parkinson’s disease. Curr Opin Neurobiol. 2014;29:109–17.

    CAS  Google Scholar 

  5. Giordano N, Iemolo A, Mancini M, Cacace F, De Risi M, Latagliata EC, et al. Motor learning and metaplasticity in striatal neurons: relevance for Parkinson’s disease. Brain. 2018;141:505–20.

    Google Scholar 

  6. Girasole AE, Lum MY, Nathaniel D, Bair-Marshall CJ, Guenthner CJ, Luo L, et al. A Subpopulation of Striatal Neurons Mediates Levodopa-Induced Dyskinesia. Neuron. 2018;97:787–95.e6.

    CAS  Google Scholar 

  7. Pisani A, Centonze D, Bernardi G, Calabresi P. Striatal synaptic plasticity: implications for motor learning and Parkinson’s disease. Mov Disord. 2005;20:395–402.

    Google Scholar 

  8. Gerfen CR, Surmeier DJ. Modulation of striatal projection systems by dopamine. Annu Rev Neurosci. 2011;34:441–66.

    CAS  Google Scholar 

  9. Zhai S, Shen W, Graves SM, Surmeier DJ. Dopaminergic modulation of striatal function and Parkinson’s disease. J Neural Transm. 2019;126:411–22.

    CAS  Google Scholar 

  10. Calabresi P, Picconi B, Tozzi A, Ghiglieri V, Di, Filippo M. Direct and indirect pathways of basal ganglia: a critical reappraisal. Nat Neurosci. 2014;17:1022–30.

    CAS  Google Scholar 

  11. Gerfen CR, Young WS 3rd. 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. 1988;460:161–7.

    CAS  Google Scholar 

  12. Shen W, Flajolet M, Greengard P, Surmeier DJ. Dichotomous dopaminergic control of striatal synaptic plasticity. Science 2008;321:848–51.

    CAS  Google Scholar 

  13. Higley MJ, Sabatini BL. Competitive regulation of synaptic Ca2+ influx by D2 dopamine and A2A adenosine receptors. Nat Neurosci. 2010;13:958–66.

    CAS  Google Scholar 

  14. Kozorovitskiy Y, Peixoto R, Wang W, Saunders A, Sabatini BL. Neuromodulation of excitatory synaptogenesis in striatal development. Elife. 2015;4:e10111.

  15. Shen W, Plotkin JL, Francardo V, Ko WK, Xie Z, Li Q, et al. M4 Muscarinic Receptor Signaling Ameliorates Striatal Plasticity Deficits in Models of L-DOPA-Induced Dyskinesia. Neuron. 2015;88:762–73.

    CAS  Google Scholar 

  16. Yan Z, Flores-Hernandez J, Surmeier DJ. Coordinated expression of muscarinic receptor messenger RNAs in striatal medium spiny neurons. Neuroscience. 2001;103:1017–24.

    CAS  Google Scholar 

  17. Bernard V, Normand E, Bloch B. Phenotypical characterization of the rat striatal neurons expressing muscarinic receptor genes. J Neurosci. 1992;12:3591–600.

    CAS  Google Scholar 

  18. Hersch SM, Gutekunst CA, Rees HD, Heilman CJ, Levey AI. Distribution of m1-m4 muscarinic receptor proteins in the rat striatum: light and electron microscopic immunocytochemistry using subtype-specific antibodies. J Neurosci. 1994;14:3351–63.

    CAS  Google Scholar 

  19. Tejeda HA, Wu J, Kornspun AR, Pignatelli M, Kashtelyan V, Krashes MJ, et al. Pathway- and Cell-Specific Kappa-Opioid Receptor Modulation of Excitation-Inhibition Balance Differentially Gates D1 and D2 Accumbens Neuron Activity. Neuron. 2017;93:147–63.

    CAS  Google Scholar 

  20. Oude Ophuis RJ, Boender AJ, van Rozen AJ, Adan RA. Cannabinoid, melanocortin and opioid receptor expression on DRD1 and DRD2 subpopulations in rat striatum. Front Neuroanat. 2014;8:14.

    Google Scholar 

  21. Reiner A, Anderson KD. The patterns of neurotransmitter and neuropeptide co-occurrence among striatal projection neurons: conclusions based on recent findings. Brain Res Brain Res Rev. 1990;15:251–65.

    CAS  Google Scholar 

  22. Di Chiara G, Imperato A. Drugs abused by humans preferentially increase synaptic dopamine concentrations in the mesolimbic system of freely moving rats. Proc Natl Acad Sci USA. 1988;85:5274–8.

    Google Scholar 

  23. Spanagel R, Herz A, Shippenberg TS. Opposing tonically active endogenous opioid systems modulate the mesolimbic dopaminergic pathway. Proc Natl Acad Sci USA. 1992;89:2046–50.

    CAS  Google Scholar 

  24. Ehrich JM, Messinger DI, Knakal CR, Kuhar JR, Schattauer SS, Bruchas MR, et al. Kappa Opioid Receptor-Induced Aversion Requires p38 MAPK Activation in VTA Dopamine Neurons. J Neurosci. 2015;35:12917–31.

    CAS  Google Scholar 

  25. Mu P, Neumann PA, Panksepp J, Schluter OM, Dong Y. Exposure to cocaine alters dynorphin-mediated regulation of excitatory synaptic transmission in nucleus accumbens neurons. Biol Psychiatry. 2011;69:228–35.

    CAS  Google Scholar 

  26. Coleman BC, Manz KM, Grueter BA Kappa opioid receptor modulation of excitatory drive onto nucleus accumbens fast-spiking interneurons. Neuropsychopharmacology. 2021;46:2340–9.

  27. Atwood BK, Kupferschmidt DA, Lovinger DM. Opioids induce dissociable forms of long-term depression of excitatory inputs to the dorsal striatum. Nat Neurosci. 2014;17:540–8.

    CAS  Google Scholar 

  28. Gong S, Doughty M, Harbaugh CR, Cummins A, Hatten ME, Heintz N, et al. Targeting Cre recombinase to specific neuron populations with bacterial artificial chromosome constructs. J Neurosci. 2007;27:9817–23.

    CAS  Google Scholar 

  29. Lee EC, Yu D, Martinez de Velasco J, Tessarollo L, Swing DA, Court DL, et al. A highly efficient Escherichia coli-based chromosome engineering system adapted for recombinogenic targeting and subcloning of BAC DNA. Genomics. 2001;73:56–65.

    CAS  Google Scholar 

  30. Li Y, van den Pol AN. Differential target-dependent actions of coexpressed inhibitory dynorphin and excitatory hypocretin/orexin neuropeptides. J Neurosci. 2006;26:13037–47.

    CAS  Google Scholar 

  31. Wu YW, Kim JI, Tawfik VL, Lalchandani RR, Scherrer G, Ding JB. Input- and cell-type-specific endocannabinoid-dependent LTD in the striatum. Cell Rep. 2015;10:75–87.

    CAS  Google Scholar 

  32. Castane A, Theobald DE, Robbins TW. Selective lesions of the dorsomedial striatum impair serial spatial reversal learning in rats. Behav Brain Res. 2010;210:74–83.

    Google Scholar 

  33. Ineichen C, Sigrist H, Spinelli S, Lesch KP, Sautter E, Seifritz E, et al. Establishing a probabilistic reversal learning test in mice: evidence for the processes mediating reward-stay and punishment-shift behaviour and for their modulation by serotonin. Neuropharmacology. 2012;63:1012–21.

    CAS  Google Scholar 

  34. Richardson NR, Roberts DC. Progressive ratio schedules in drug self-administration studies in rats: a method to evaluate reinforcing efficacy. J Neurosci Methods. 1996;66:1–11.

    CAS  Google Scholar 

  35. Johnson C, Wilbrecht L. Juvenile mice show greater flexibility in multiple choice reversal learning than adults. Dev Cogn Neurosci. 2011;1:540–51.

    Google Scholar 

  36. Luo SX, Timbang L, Kim JI, Shang Y, Sandoval K, Tang AA, et al. TGF-beta Signaling in Dopaminergic Neurons Regulates Dendritic Growth, Excitatory-Inhibitory Synaptic Balance, and Reversal Learning. Cell Rep. 2016;17:3233–45.

    CAS  Google Scholar 

  37. Healy DJ, Meador-Woodruff JH. Prodynorphin-derived peptide expression in primate cortex and striatum. Neuropeptides. 1994;27:277–84.

    CAS  Google Scholar 

  38. Schwarzer C. 30 years of dynorphins—new insights on their functions in neuropsychiatric diseases. Pharm Ther. 2009;123:353–70.

    CAS  Google Scholar 

  39. Schlosser B, Kudernatsch MB, Sutor B, ten Bruggencate G. Delta, mu and kappa opioid receptor agonists inhibit dopamine overflow in rat neostriatal slices. Neurosci Lett. 1995;191:126–30.

    CAS  Google Scholar 

  40. Hjelmstad GO, Fields HL. Kappa opioid receptor inhibition of glutamatergic transmission in the nucleus accumbens shell. J Neurophysiol. 2001;85:1153–8.

    CAS  Google Scholar 

  41. Hjelmstad GO, Fields HL. Kappa opioid receptor activation in the nucleus accumbens inhibits glutamate and GABA release through different mechanisms. J Neurophysiol. 2003;89:2389–95.

    CAS  Google Scholar 

  42. Watabe-Uchida M, Eshel N, Uchida N. Neural Circuitry of Reward Prediction Error. Annu Rev Neurosci. 2017;40:373–94.

    CAS  Google Scholar 

  43. Schultz W, Dayan P, Montague PR. A neural substrate of prediction and reward. Science. 1997;275:1593–9.

    CAS  Google Scholar 

  44. Centonze D, Grande C, Saulle E, Martin AB, Gubellini P, Pavon N, et al. Distinct roles of D1 and D5 dopamine receptors in motor activity and striatal synaptic plasticity. J Neurosci. 2003;23:8506–12.

    CAS  Google Scholar 

  45. Yin HH, Ostlund SB, Balleine BW. Reward-guided learning beyond dopamine in the nucleus accumbens: the integrative functions of cortico-basal ganglia networks. Eur J Neurosci. 2008;28:1437–48.

    Google Scholar 

  46. Balleine BW, O’Doherty JP. Human and rodent homologies in action control: corticostriatal determinants of goal-directed and habitual action. Neuropsychopharmacology. 2010;35:48–69.

    Google Scholar 

  47. Albarran E, Raissi A, Jaidar O, Shatz CJ, Ding JB. Enhancing motor learning by increasing the stability of newly formed dendritic spines in the motor cortex. Neuron 2021;109:3298–311.e4.

    CAS  Google Scholar 

  48. Clem RL, Celikel T, Barth AL. Ongoing in vivo experience triggers synaptic metaplasticity in the neocortex. Science. 2008;319:101–4.

    CAS  Google Scholar 

  49. Rioult-Pedotti MS, Friedman D, Donoghue JP. Learning-induced LTP in neocortex. Science. 2000;290:533–6.

    CAS  Google Scholar 

  50. Izquierdo A, Brigman JL, Radke AK, Rudebeck PH, Holmes A. The neural basis of reversal learning: An updated perspective. Neuroscience. 2017;345:12–26.

    CAS  Google Scholar 

  51. Carlezon WA Jr., Beguin C, DiNieri JA, Baumann MH, Richards MR, Todtenkopf MS, et al. Depressive-like effects of the kappa-opioid receptor agonist salvinorin A on behavior and neurochemistry in rats. J Pharm Exp Ther. 2006;316:440–7.

    CAS  Google Scholar 

  52. Negus SS. Effects of the kappa opioid agonist U50,488 and the kappa opioid antagonist nor-binaltorphimine on choice between cocaine and food in rhesus monkeys. Psychopharmacology. 2004;176:204–13.

    Google Scholar 

  53. Schindler AG, Li S, Chavkin C. Behavioral stress may increase the rewarding valence of cocaine-associated cues through a dynorphin/kappa-opioid receptor-mediated mechanism without affecting associative learning or memory retrieval mechanisms. Neuropsychopharmacology. 2010;35:1932–42.

    CAS  Google Scholar 

  54. Todtenkopf MS, Marcus JF, Portoghese PS, Carlezon WA Jr. Effects of kappa-opioid receptor ligands on intracranial self-stimulation in rats. Psychopharmacology. 2004;172:463–70.

    CAS  Google Scholar 

  55. Edwards NJ, Tejeda HA, Pignatelli M, Zhang S, McDevitt RA, Wu J, et al. Circuit specificity in the inhibitory architecture of the VTA regulates cocaine-induced behavior. Nat Neurosci. 2017;20:438–48.

    CAS  Google Scholar 

  56. Nestler EJ. Historical review: Molecular and cellular mechanisms of opiate and cocaine addiction. Trends Pharm Sci. 2004;25:210–8.

    CAS  Google Scholar 

  57. Drake CT, Terman GW, Simmons ML, Milner TA, Kunkel DD, Schwartzkroin PA, et al. Dynorphin opioids present in dentate granule cells may function as retrograde inhibitory neurotransmitters. J Neurosci. 1994;14:3736–50.

    CAS  Google Scholar 

  58. Terman GW, Wagner JJ, Chavkin C. Kappa opioids inhibit induction of long-term potentiation in the dentate gyrus of the guinea pig hippocampus. J Neurosci. 1994;14:4740–7.

    CAS  Google Scholar 

  59. Wagner JJ, Terman GW, Chavkin C. Endogenous dynorphins inhibit excitatory neurotransmission and block LTP induction in the hippocampus. Nature. 1993;363:451–4.

    CAS  Google Scholar 

  60. Weisskopf MG, Zalutsky RA, Nicoll RA. The opioid peptide dynorphin mediates heterosynaptic depression of hippocampal mossy fibre synapses and modulates long-term potentiation. Nature. 1993;365:188.

    CAS  Google Scholar 

  61. Polter AM, Bishop RA, Briand LA, Graziane NM, Pierce RC, Kauer JA. Poststress block of kappa opioid receptors rescues long-term potentiation of inhibitory synapses and prevents reinstatement of cocaine seeking. Biol Psychiatry. 2014;76:785–93.

    CAS  Google Scholar 

  62. Graziane NM, Polter AM, Briand LA, Pierce RC, Kauer JA. Kappa opioid receptors regulate stress-induced cocaine seeking and synaptic plasticity. Neuron. 2013;77:942–54.

    CAS  Google Scholar 

  63. Hawes SL, Salinas AG, Lovinger DM, Blackwell KT. Long-term plasticity of corticostriatal synapses is modulated by pathway-specific co-release of opioids through kappa-opioid receptors. J Physiol. 2017;595:5637–52.

    CAS  Google Scholar 

  64. Svingos AL, Chavkin C, Colago EE, Pickel VM. Major coexpression of kappa-opioid receptors and the dopamine transporter in nucleus accumbens axonal profiles. Synapse. 2001;42:185–92.

    CAS  Google Scholar 

  65. Gentleman S, Parenti M, Neff NH, Pert CB. Inhibition of dopamine-activated adenylate cyclase and dopamine binding by opiate receptors in rat striatum. Cell Mol Neurobiol. 1983;3:17–26.

    CAS  Google Scholar 

  66. Bruchas MR, Chavkin C. Kinase cascades and ligand-directed signaling at the kappa opioid receptor. Psychopharmacology. 2010;210:137–47.

    CAS  Google Scholar 

  67. Augustin SM, Beeler JA, McGehee DS, Zhuang X. Cyclic AMP and afferent activity govern bidirectional synaptic plasticity in striatopallidal neurons. J Neurosci. 2014;34:6692–9.

    CAS  Google Scholar 

  68. Lerner TN, Kreitzer AC. RGS4 Is Required for Dopaminergic Control of Striatal LTD and Susceptibility to Parkinsonian Motor Deficits. Neuron. 2012;73:347–59.

    CAS  Google Scholar 

  69. Van’t Veer A, Carlezon WA Jr. Role of kappa-opioid receptors in stress and anxiety-related behavior. Psychopharmacology. 2013;229:435–52.

    Google Scholar 

  70. Land BB, Bruchas MR, Lemos JC, Xu M, Melief EJ, Chavkin C. The dysphoric component of stress is encoded by activation of the dynorphin kappa-opioid system. J Neurosci. 2008;28:407–14.

    CAS  Google Scholar 

  71. Crowley NA, Bloodgood DW, Hardaway JA, Kendra AM, McCall JG, Al-Hasani R, et al. Dynorphin Controls the Gain of an Amygdalar Anxiety Circuit. Cell Rep. 2016;14:2774–83.

    CAS  Google Scholar 

  72. Soares-Cunha C, de Vasconcelos NAP, Coimbra B, Domingues AV, Silva JM, Loureiro-Campos E, et al. Nucleus accumbens medium spiny neurons subtypes signal both reward and aversion. Mol Psychiatry. 2020;25:3241–55.

    CAS  Google Scholar 

  73. Carey AN, Lyons AM, Shay CF, Dunton O, McLaughlin JP. Endogenous kappa opioid activation mediates stress-induced deficits in learning and memory. J Neurosci. 2009;29:4293–300.

    CAS  Google Scholar 

  74. Hiramatsu M, Hoshino T. Involvement of kappa-opioid receptors and sigma receptors in memory function demonstrated using an antisense strategy. Brain Res. 2004;1030:247–55.

    CAS  Google Scholar 

  75. Kuzmin A, Madjid N, Terenius L, Ogren SO, Bakalkin G. Big dynorphin, a prodynorphin-derived peptide produces NMDA receptor-mediated effects on memory, anxiolytic-like and locomotor behavior in mice. Neuropsychopharmacology. 2006;31:1928–37.

    CAS  Google Scholar 

  76. Ukai M, Itoh J, Kobayashi T, Shinkai N, Kameyama T. Effects of the kappa-opioid dynorphin A(1-13) on learning and memory in mice. Behav Brain Res. 1997;83:169–72.

    CAS  Google Scholar 

  77. Braun S, Hauber W. The dorsomedial striatum mediates flexible choice behavior in spatial tasks. Behav Brain Res. 2011;220:288–93.

    Google Scholar 

  78. Darvas M, Palmiter RD. Specific contributions of N-methyl-D-aspartate receptors in the dorsal striatum to cognitive flexibility. Neuroscience. 2015;284:934–42.

    CAS  Google Scholar 

  79. Izquierdo A, Wiedholz LM, Millstein RA, Yang RJ, Bussey TJ, Saksida LM, et al. Genetic and dopaminergic modulation of reversal learning in a touchscreen-based operant procedure for mice. Behav Brain Res. 2006;171:181–8.

    CAS  Google Scholar 

  80. Boulougouris V, Castane A, Robbins TW. Dopamine D2/D3 receptor agonist quinpirole impairs spatial reversal learning in rats: investigation of D3 receptor involvement in persistent behavior. Psychopharmacology. 2009;202:611–20.

    CAS  Google Scholar 

  81. Al-Hasani R, McCall JG, Shin G, Gomez AM, Schmitz GP, Bernardi JM, et al. Distinct Subpopulations of Nucleus Accumbens Dynorphin Neurons Drive Aversion and Reward. Neuron. 2015;87:1063–77.

    CAS  Google Scholar 

  82. Kim J, Zhang X, Muralidhar S, LeBlanc SA, Tonegawa S. Basolateral to Central Amygdala Neural Circuits for Appetitive Behaviors. Neuron. 2017;93:1464–79.e5.

    CAS  Google Scholar 

  83. Li MM, Madara JC, Steger JS, Krashes MJ, Balthasar N, Campbell JN, et al. The Paraventricular Hypothalamus Regulates Satiety and Prevents Obesity via Two Genetically Distinct Circuits. Neuron. 2019;102:653–67.e6.

    CAS  Google Scholar 

  84. Pina MM, Pati D, Hwa LS, Wu SY, Mahoney AA, Omenyi CG, et al. The kappa opioid receptor modulates GABA neuron excitability and synaptic transmission in midbrainprojections from the insular cortex. Neuropharmacology. 2020;165:107831.

    CAS  Google Scholar 

  85. Grospe GM, Baker PM, Ragozzino ME. Cognitive Flexibility Deficits Following 6-OHDA Lesions of the Rat Dorsomedial Striatum. Neuroscience. 2018;374:80–90.

    CAS  Google Scholar 

  86. Izquierdo A, Jentsch JD. Reversal learning as a measure of impulsive and compulsive behavior in addictions. Psychopharmacology. 2012;219:607–20.

    CAS  Google Scholar 

  87. Richfield EK, Penney JB, Young AB. Anatomical and affinity state comparisons between dopamine D1 and D2 receptors in the rat central nervous system. Neuroscience. 1989;30:767–77.

    CAS  Google Scholar 

  88. Evers EA, Cools R, Clark L, van der Veen FM, Jolles J, Sahakian BJ, et al. Serotonergic modulation of prefrontal cortex during negative feedback in probabilistic reversal learning. Neuropsychopharmacology. 2005;30:1138–47.

    CAS  Google Scholar 

  89. Murphy FC, Michael A, Robbins TW, Sahakian BJ. Neuropsychological impairment in patients with major depressive disorder: the effects of feedback on task performance. Psychol Med. 2003;33:455–67.

    CAS  Google Scholar 

  90. Lea SEG, Chow PKY, Leaver LA, McLaren IPL. Behavioral flexibility: A review, a model, and some exploratory tests. Learn Behav. 2020;48:173–87.

    Google Scholar 

  91. Tello-Ramos MC, Branch CL, Kozlovsky DY, Pitera AM, Pravosudov VV. Spatial memory and cognitive flexibility trade-offs: to be or not to be flexible, that is the question. Anim Behav. 2019;147:129–36.

    Google Scholar 

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Acknowledgements

We thank Dr. Eddy Albarran, Dr. Richard Roth for advice on the paper, Drs. Yu Liu and Xiaobai Ren for technical assistance, and the members of Ding lab for valuable discussions. This work was funded by NINDS/NIH NS091144 (to JBD), NS107315, DK108797, DK046200 (to DK) the GG gift fund (to JBD), the Stanford Bio-X Bowes Graduate Student Fellowship (to RY), and Stanford Neuroscience Institute Interdisciplinary Scholar Awards (to R.R.L.)

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RY, RRL, and JBD conceived this project. RY performed electrophysiology recording and operant chamber behavior experiments. RRL characterized lox-pDyn mice, and performed immunostaining and behavioral experiments. FJH performed the spine imaging. DK and JBD designed and generated lox-pDyn mice. RY and RRL analyzed the data. RY, RRL, DWB and JBD wrote the paper with input from all authors.

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Correspondence to Jun B. Ding.

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Yang, R., Tuan, R.R.L., Hwang, FJ. et al. Dichotomous regulation of striatal plasticity by dynorphin. Mol Psychiatry 28, 434–447 (2023). https://doi.org/10.1038/s41380-022-01885-0

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