1932

Abstract

In recent years, the population of neurons in the ventral tegmental area (VTA) and substantia nigra (SN) has been examined at multiple levels. The results indicate that the projections, neurochemistry, and receptor and ion channel expression in this cell population vary widely. This review centers on the intrinsic properties and synaptic regulation that control the activity of dopamine neurons. Although all dopamine neurons fire action potentials in a pacemaker pattern in the absence of synaptic input, the intrinsic properties that underlie this activity differ considerably. Likewise, the transition into a burst/pause pattern results from combinations of intrinsic ion conductances, inhibitory and excitatory synaptic inputs that differ among this cell population. Finally, synaptic plasticity is a key regulator of the rate and pattern of activity in different groups of dopamine neurons. Through these fundamental properties, the activity of dopamine neurons is regulated and underlies the wide-ranging functions that have been attributed to dopamine.

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2018-02-10
2024-06-12
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Literature Cited

  1. Björklund A, Dunnett SB. 1.  2007. Dopamine neuron systems in the brain: an update. Trends Neurosci 30:194–202 [Google Scholar]
  2. Oades RD, Halliday GM. 2.  1987. Ventral tegmental (A10) system: neurobiology. 1. Anatomy and connectivity. Brain Res. Rev. 12:117–65 [Google Scholar]
  3. Fallon JH, Loughlin SE. 3.  1975. Substantia nigra. The Rat Central Nervous System G Paxinos 215–37 New York: Academic [Google Scholar]
  4. Phillipson OT.4.  1979. A Golgi study of the ventral tegmental area of Tsai and interfascicular nucleus in the rat. J. Comp. Neurol. 187:99–116 [Google Scholar]
  5. Evans RC, Zhu M, Khaliq ZM. 5.  2017. Dopamine inhibition differentially controls excitability of SNc dopamine neuron subpopulations through recruitment of T-type calcium channels. J. Neurosci. 37:3704–20 [Google Scholar]
  6. Henny P, Brown MT, Northrop A, Faunes M, Ungless MA. 6.  et al. 2012. Structural correlates of heterogeneous in vivo activity of midbrain dopaminergic neurons. Nat. Neurosci. 15:613–19 [Google Scholar]
  7. Jang M, Um KB, Jang J, Kim HJ, Cho H. 7.  et al. 2015. Coexistence of glutamatergic spine synapses and shaft synapses in substantia nigra dopamine neurons. Sci. Rep. 5:14773 [Google Scholar]
  8. Hage TA, Sun Y, Khaliq ZM. 8.  2016. Electrical and Ca2+ signaling in dendritic spines of substantia nigra dopaminergic neurons. eLife 5:e13905 [Google Scholar]
  9. Fortin DA, Tilo SE, Yang G, Melander JB, Bai S. 9.  et al. 2014. Live imaging of endogenous PSD-95 using ENABLE: a conditional strategy to fluorescently label endogenous proteins. J. Neurosci. 34:16698–712 [Google Scholar]
  10. Gantz SC, Robinson BG, Buck DC, Bunzow JR, Neve RL. 10.  et al. 2015. Distinct regulation of dopamine D2S and D2L autoreceptor signaling by calcium. eLife 4:e09358 [Google Scholar]
  11. Gantz SC, Bunzow JR, Williams JT. 11.  2013. Spontaneous inhibitory synaptic currents mediated by a G protein-coupled receptor. Neuron 78:807–12 [Google Scholar]
  12. Robinson BG, Bunzow JR, Grimm JB, Lavis LD, Dudman JT. 12.  et al. 2017. Desensitized D2 autoreceptors are resistant to trafficking. Cell Rep 7:4379 [Google Scholar]
  13. Sesack SR, Aoki C, Pickel VM. 13.  1994. Ultrastructural localization of D2 receptor-like immunoreactivity in midbrain dopamine neurons and their striatal targets. J. Neurosci. 14:88–106 [Google Scholar]
  14. Balcita-Pedicino JJ, Omelchenko N, Bell R, Sesack SR. 14.  2010. The inhibitory influence of the lateral habenula on midbrain dopamine cells: ultrastructural evidence of indirect mediation via the rostromedial mesopontine tegmental nucleus. J. Comp. Neurol. 519:1143–64 [Google Scholar]
  15. Häusser M, Stuart G, Racca C, Sakmann B. 15.  1995. Axonal initiation and active dendritic propagation of action potentials in substantia nigra neurons. Neuron 15:637–47 [Google Scholar]
  16. Vetter P, Roth A, Häusser M. 16.  2001. Propagation of action potential in dendrites depends on dendritic morphology. J. Neurophys. 85:926–37 [Google Scholar]
  17. Blythe SN, Wokosin D, Atherton JF, Bevan MD. 17.  2009. Cellular mechanisms underlying burst firing in substantia nigra dopamine neurons. J. Neurosci. 29:15531–41 [Google Scholar]
  18. Hage TA, Khaliq ZM. 18.  2015. Tonic firing rate controls dendritic Ca2+ signaling and synaptic gain in substantia nigra dopamine neurons. J. Neurosci. 35:5823–36 [Google Scholar]
  19. Liss B, Roeper J. 19.  2008. Individual dopamine midbrain neurons: functional diversity and flexibility in health and disease. Brain Res. Rev. 58:314–21 [Google Scholar]
  20. Wilson CJ, Callaway JC. 20.  2000. Coupled oscillator model of the dopaminergic neurons of the substantia nigra. J. Neurophys. 83:3084–100 [Google Scholar]
  21. Kang Y, Kitai ST. 21.  1993. A whole cell patch-clamp study on the pacemaker potential in dopaminergic neurons of rat substantia nigra compacta. Neurosci. Res. 18:209–21 [Google Scholar]
  22. Khaliq ZM, Bean BP. 22.  2010. Pacemaking in dopaminergic ventral tegmental area neurons: depolarizing drive from background and voltage-dependent sodium conductances. J. Neurosci. 30:7401–13 [Google Scholar]
  23. Puopolo M, Raviola E, Bean BP. 23.  2007. Roles of subthreshold calcium current and sodium current in spontaneous firing of mouse midbrain dopamine neurons. J. Neurosci. 27:645–56 [Google Scholar]
  24. Hage TA, Sun Y, Khaliq ZM. 24.  2016. Electrical and Ca2+ signaling in dendritic spines of substantia nigra dopaminergic neurons. eLife 5:17961 [Google Scholar]
  25. Wang W, Touhara KK, Weir K, Bean BP, MacKinnon R. 25.  2016. Cooperative regulation by G proteins and Na+ of neuronal GIRK2 K+ channels. eLife 5:852 [Google Scholar]
  26. Lu TZ, Feng Z-P. 26.  2012. NALCN: a regulator of pacemaker activity. Mol. Neurobiol. 45:415–23 [Google Scholar]
  27. Puopolo M, Raviola E, Bean BP. 27.  2007. Roles of subthreshold calcium current and sodium current in spontaneous firing of mouse midbrain dopamine neurons. J. Neurosci. 27:645–56 [Google Scholar]
  28. Branch SY, Sharma R, Beckstead MJ. 28.  2014. Aging decreases L-type calcium channel currents and pacemaker firing fidelity in substantia nigra dopamine neurons. J. Neurosci. 34:9310–18 [Google Scholar]
  29. Chan CS, Guzman JN, Ilijic E, Mercer JN, Rick C. 29.  et al. 2007. “Rejuvenation” protects neurons in mouse models of Parkinson's disease. Nature 447:1081–86 [Google Scholar]
  30. Guzman JN, Sánchez-Padilla J, Chan CS, Surmeier DJ. 30.  2009. Robust pacemaking in substantia nigra dopaminergic neurons. J. Neurosci. 29:11011–19 [Google Scholar]
  31. Poetschke C, Dragicevic E, Duda J, Benkert J, Dougalis A. 31.  et al. 2015. Compensatory T-type Ca2+ channel activity alters D2-autoreceptor responses of Substantia nigra dopamine neurons from Cav1.3 L-type Ca2+ channel KO mice. Sci. Rep. 5:13688 [Google Scholar]
  32. Dragicevic E, Poetschke C, Duda J, Schlaudraff F, Lammel S. 32.  et al. 2014. Cav1.3 channels control D2-autoreceptor responses via NCS-1 in substantia nigra dopamine neurons. Brain 137:2287–302 [Google Scholar]
  33. Dufour MA, Woodhouse A, Goaillard J-M. 33.  2014. Somatodendritic ion channel expression in substantia nigra pars compacta dopaminergic neurons across postnatal development. J. Neurosci. Res. 92:981–99 [Google Scholar]
  34. Wolfart J, Roeper J. 34.  2002. Selective coupling of T-type calcium channels to SK potassium channels prevents intrinsic bursting in dopaminergic midbrain neurons. J. Neurosci. 22:3404–13 [Google Scholar]
  35. Cui G, Okamoto T, Morikawa H. 35.  2004. Spontaneous opening of T-type Ca2+ channels contributes to the irregular firing of dopamine neurons in neonatal rats. J. Neurosci. 24:11079–87 [Google Scholar]
  36. Ford CP, Beckstead MJ, Williams JT. 36.  2007. Kappa opioid inhibition of somatodendritic dopamine inhibitory postsynaptic currents. J. Neurophysiol. 97:883–91 [Google Scholar]
  37. Beckstead MJ, Grandy DK, Wickman K, Williams JT. 37.  2004. Vesicular dopamine release elicits an inhibitory postsynaptic current in midbrain dopamine neurons. Neuron 42:939–46 [Google Scholar]
  38. Durante P, Cardenas CG, Whittaker JA, Kitai ST, Scroggs RS. 38.  2004. Low-threshold L-type calcium channels in rat dopamine neurons. J. Neurophysiol. 91:1450–54 [Google Scholar]
  39. Pian P, Bucchi A, Robinson RB, Siegelbaum SA. 39.  2006. Regulation of gating and rundown of HCN hyperpolarization-activated channels by exogenous and endogenous PIP2. J. Gen. Physiol. 128:593–604 [Google Scholar]
  40. Zolles G, Klöcker N, Wenzel D, Weisser-Thomas J, Fleischmann BK. 40.  et al. 2006. Pacemaking by HCN channels requires interaction with phosphoinositides. Neuron 52:1027–36 [Google Scholar]
  41. Neuhoff H, Neu A, Liss B, Roeper J. 41.  2002. Ih channels contribute to the different functional properties of identified dopaminergic subpopulations in the midbrain. J. Neurosci. 22:1290–302 [Google Scholar]
  42. Lammel S, Ion DI, Roeper J, Malenka RC. 42.  2011. Projection-specific modulation of dopamine neuron synapses by aversive and rewarding stimuli. Neuron 70:855–62 [Google Scholar]
  43. Seutin V, Massotte L, Renette MF, Dresse A. 43.  2001. Evidence for a modulatory role of Ih on the firing of a subgroup of midbrain dopamine neurons. NeuroReport 12:255–58 [Google Scholar]
  44. Amendola J, Woodhouse A, Martin-Eauclaire M-F, Goaillard JM. 44.  2012. Ca2+/cAMP-sensitive covariation of IA and IH voltage dependences tunes rebound firing in dopaminergic neurons. J. Neurosci. 32:2166–81 [Google Scholar]
  45. Connor JA, Stevens CF. 45.  1971. Voltage clamp study of a transient outward membrane current in gastropod neural somata. J. Physiol. 213:21–30 [Google Scholar]
  46. Jerng HH, Pfaffinger PJ, Covarrubias M. 46.  2004. Molecular physiology and modulation of somtodendritic A-type potassium channels. Mol. Cell. Neurosci. 27:434–69 [Google Scholar]
  47. Liss B, Frans O, Sewing S, Bruns R, Neuhoff H. 47.  et al. 2001. Tuning pacemaker frequency of individual dopaminergic neurons by Kv4.3L and KChip3.1 transcription. EMBO J 20:5715–24 [Google Scholar]
  48. Koyama S, Appel SB. 48.  2006. A-type K+ current of dopamine and GABA neurons in the ventral tegmental area. J. Neurophysiol. 96:544–54 [Google Scholar]
  49. Gentet LJ, Williams SR. 49.  2007. Dopamine gates action potential backpropagation in midbrain dopaminergic neurons. J. Neurosci. 27:1892–901 [Google Scholar]
  50. Khaliq ZM, Bean BP. 50.  2008. Dynamic, nonlinear feedback regulation of slow pacemaking by A-type potassium current in ventral tegmental area neurons. J. Neurosci. 28:10905–17 [Google Scholar]
  51. Gantz SC, Bean BP. 51.  2017. Cell-autonomous excitation of midbrain dopamine neurons by endocannabinoid-dependent lipid signaling. Neuron 93:1375–87 [Google Scholar]
  52. Hahn RG, Tse TE, Levitan ES. 52.  2003. Long-term K channel-mediated dampening of dopamine neurons excitability by the antipsychotic drug haloperidol. J. Neurosci. 23:10859–66 [Google Scholar]
  53. Subramaniam M, Althof D, Gispert S, Schwenk J, Auburger G. 53.  et al. 2014. Mutant α-synuclein enhances firing frequencies in dopamine substantia nigra neurons by oxidative impairment of A-type potassium channels. J. Neurosci. 34:13586–99 [Google Scholar]
  54. Tarfa RA, Evans RC, Khaliq ZM. 54.  2017. Enhanced sensitivity to hyperpolarizing inhibition in mesoaccumbal relative to nigrostriatal dopamine neurons subpopulations. J. Neurosci. 37:3311–30 [Google Scholar]
  55. An WF, Bowlby MR, Betty M, Cao J, Ling HP. 55.  et al. 2000. Modulation of A-type potassium channels by a family of calcium sensors. Nature 403:553–56 [Google Scholar]
  56. Yang F, Feng L, Zheng F, Johnson SW, Du J. 56.  et al. 2001. GDNF acutely modulates excitability and A-type K channels in midbrain dopaminergic neurons. Nat. Neurosci. 4:1071–78 [Google Scholar]
  57. Fiorillo CD, Williams JT. 57.  1998. Glutamate mediates an inhibitory postsynaptic potential in dopamine neurons. Nature 394:78–82 [Google Scholar]
  58. Fiorillo CD, Williams JT.58.  2000. Cholinergic inhibition of ventral midbrain dopamine neurons. J. Neurosci. 20:7855–60 [Google Scholar]
  59. Morikawa H, Khodakhah K, Williams JT. 59.  2003. Two intracellular pathways mediated metabotropic glutamate receptor-induced Ca mobilization in dopamine neurons. J. Neurosci. 23:149–57 [Google Scholar]
  60. Paladini CA, Williams JT. 60.  2004. Noradrenergic inhibition of midbrain dopamine neurons. J. Neurosci. 24:4568–75 [Google Scholar]
  61. Kramer PF, Williams JT. 61.  2016. Calcium release from stores inhibits GIRK. Cell Rep 17:3246–55 [Google Scholar]
  62. Wolfart J, Neuhoff H, Franz O, Roeper J. 62.  2001. Differential expression of the small-conductance, calcium-activated potassium channel SK3 is critical for pacemaker control in dopaminergic midbrain neurons. J. Neurosci. 21:3443–56 [Google Scholar]
  63. Hansen HH, Ebbesen C, Mathiesen C, Weikop P, Rønn LC. 63.  et al. 2006. The KCNQ channel opener retigabine inhibits the activity of mesencephalic dopaminergic systems of the rat. J. Pharmacol. Exp. Ther. 318:1006–19 [Google Scholar]
  64. Drion G, Bonjean M, Waroux O, Scuvée-Moreau J, Liégeois JF. 64.  et al. 2010. M-type channels selectively control bursting in rat dopaminergic neurons. Eur. J. Neurosci. 31:827–35 [Google Scholar]
  65. Kimm T, Khaliq ZM, Bean BP. 65.  2015. Differential regulation of action potential shape and burst-frequency firing by BK and Kv2 channels in substantia nigra dopaminergic neurons. J. Neurosci. 35:16404–17 [Google Scholar]
  66. McCall NM, Koteki L, Dominguez-Lopez S, Fernandez de Velasco EM, Carlblom N. 66.  et al. 2017. Selective ablation of GIRK channels in dopamine neurons alters behavioral effects of cocaine in mice. Neuropsychopharmacology 42:707–15 [Google Scholar]
  67. Lujan R, Aguado C. 67.  2015. Localization and targeting of GIRK channels in mammalian central neurons. Int. Rev. Neurobiol. 123:161–200 [Google Scholar]
  68. Lammel S, Hetzel A, Häckel O, Jones I, Liss B. 68.  et al. 2008. Unique properties of mesoprefrontal neurons within a dual mesocorticolimbic system. Neuron 57:760–73 [Google Scholar]
  69. Schiemann J, Schlaudraff F, Klose V, Bingmer M, Seino S. 69.  et al. 2012. K-ATP channels in dopamine substantia nigra neurons control bursting and novelty-induced exploration. Nat. Neurosci. 15:1272–80 [Google Scholar]
  70. Duda J, Pötschke C, Liss B. 70.  2016. Converging roles of ion channels, calcium, metabolic stress, and activity pattern of Substantia nigra dopaminergic neurons in health and Parkinson's disease. J. Neurochem. 139:156–78 [Google Scholar]
  71. Morikawa H, Paladini CA. 71.  2011. Dynamic regulation of midbrain dopamine neuron activity: intrinsic, synaptic, and plasticity mechanisms. Neuroscience 198:95–111 [Google Scholar]
  72. Beier KT, Steinberg EE, DeLoach KE, Xie S, Miyamichi K. 72.  et al. 2015. Circuit architecture of VTA dopamine neurons revealed by systematic input-output mapping. Cell 162:622–34 [Google Scholar]
  73. Faget L, Osakada F, Duan J, Ressler R, Johnson AB. 73.  et al. 2016. Afferent inputs to neurotransmitter-defined cell types in the ventral tegmental area. Cell Rep 15:2796–808 [Google Scholar]
  74. Lerner TN, Shilyansky C, Davidson TJ, Evans KE, Beier KT. 74.  et al. 2015. Intact-brain analyses reveal distinct information carried by SNc dopamine subcircuits. Cell 162:635–47 [Google Scholar]
  75. Watabe-Uchida M, Zhu L, Ogawa SK, Vamanrao A, Uchida N. 75.  2012. Whole-brain mapping of direct inputs to midbrain dopamine neurons. Neuron 74:858–73 [Google Scholar]
  76. Bayer VE, Pickel VM. 76.  1990. Ultrastructural localization of tyrosine hydroxylase in the rat ventral tegmental area: relationship between immunolabeling density and neuronal associations. J. Neurosci. 10:2996–3013 [Google Scholar]
  77. Wilson CJ, Groves PM, Fifková E. 77.  1977. Monoaminergic synapses, including dendro-dendritic synapses in the rat substantia nigra. Exp. Brain Res. 30:161–74 [Google Scholar]
  78. Nirenberg MJ, Chan J, Liu Y, Edwards RH, Pickel VM. 78.  1996. Ultrastructural localization of the vesicular monoamine transporter-2 in midbrain dopaminergic neurons: potential sites for somatodendritic storage and release of dopamine. J. Neurosci. 16:4135–45 [Google Scholar]
  79. Chen BT, Rice ME. 79.  2001. Novel Ca2+ dependence and time course of somatodendritic dopamine release: substantia nigra versus striatum. J. Neurosci. 21:7841–47 [Google Scholar]
  80. Ford CP, Gantz SC, Phillips PEM, Williams JT. 80.  2010. Control of extracellular dopamine at dendrite and axon terminals. J. Neurosci. 30:6975–83 [Google Scholar]
  81. Courtney NA, Mamaligas AA, Ford CP. 81.  2012. Species differences in somatodendritic dopamine transmission determine D2-autoreceptor-mediated inhibition of ventral tegmental area neuron firing. J. Neurosci. 32:13520–28 [Google Scholar]
  82. Sesack SR, Aoki C, Pickel VM. 82.  1994. Ultrastructural localization of D2 receptor-like immunoreactivity in midbrain dopamine neurons and their striatal targets. J. Neurosci. 14:88–106 [Google Scholar]
  83. Courtney NA, Ford CP. 83.  2014. The timing of dopamine- and noradrenaline-mediated transmission reflects underlying differences in the extent of spillover and pooling. J. Neurosci. 34:7645–56 [Google Scholar]
  84. Ford CP, Phillips PEM, Williams JT. 84.  2009. The time course of dopamine transmission in the ventral tegmental area. J. Neurosci. 29:13344–52 [Google Scholar]
  85. Rice ME, Patel JC. 85.  2015. Somatodendritic dopamine release: recent mechanistic insights. Phil. Trans. R. Soc. B 370:20140185 [Google Scholar]
  86. Mendez JA, Bourque MJ, Fasano C, Kortleven C, Trudeau LE. 86.  2011. Somatodendritic dopamine release requires synaptotagmin 4 and 7 and the participation of voltage-gated calcium channels. J. Biol. Chem. 286:23928–37 [Google Scholar]
  87. Chen BT, Moran KA, Avshalumov MV, Rice ME. 87.  2006. Limited regulation of somatodendritic dopamine release by voltage-sensitive Ca2+ channels contrasted with strong regulation of axonal dopamine release. J. Neurochem. 96:645–55 [Google Scholar]
  88. Cameron DL, Williams JT. 88.  1993. Dopamine D1 receptors facilitate transmitter release. Nature 366:344–47 [Google Scholar]
  89. Koga E, Momiyama T. 89.  2000. Presynaptic dopamine D2-like receptors inhibit excitatory transmission onto rat ventral tegmental dopaminergic neurones. J. Physiol. 523:Pt. 1163–73 [Google Scholar]
  90. Matsui A, Jarvie BC, Robinson BG, Hentges ST, Williams JT. 90.  2014. Separate GABA afferents to dopamine neurons mediate acute action of opioids, development of tolerance, and expression of withdrawal. Neuron 82:1346–56 [Google Scholar]
  91. Cameron DL, Williams JT. 91.  1994. Cocaine inhibits GABA release in the VTA through endogenous 5-HT. J. Neurosci. 14:6763–67 [Google Scholar]
  92. Kramer PF, Williams JT. 92.  2015. Cocaine decreases metabotropic glutamate receptor mGluR1 currents in dopamine neurons by activating mGluR5. Neuropsychopharmacology 40:2418–24 [Google Scholar]
  93. Piccart E, Courtney NA, Branch SY, Ford CP, Beckstead MJ. 93.  2015. Neurotensin induces presynaptic depression of D2 dopamine autoreceptor-mediated neurotransmission in midbrain dopaminergic neurons. J. Neurosci. 35:11144–52 [Google Scholar]
  94. Stuhrman K, Roseberry AG. 94.  2015. Neurotensin inhibits both dopamine- and GABA-mediated inhibition of ventral tegmental area dopamine neurons. J. Neurophysiol. 114:1734–45 [Google Scholar]
  95. Perra S, Clements MA, Bernier BE, Morikawa H. 95.  2011. In vivo ethanol experience increases D2 autoinhibition in the ventral tegmental area. Neuropsychopharmacology 36:993–1002 [Google Scholar]
  96. Sharpe AL, Varela E, Bettinger L, Beckstead MJ. 96.  2014. Methamphetamine self-administration in mice decreases GIRK channel-mediated currents in midbrain dopamine neurons. Int. J. Neuropsychopharmacol. 18:1–10 [Google Scholar]
  97. Bolam JP, Smith Y. 97.  1990. The GABA and substance P input to dopaminergic neurones in the substantia nigra of the rat. Brain Res 529:57–78 [Google Scholar]
  98. Tepper JM, Lee CR. 98.  2007. GABAergic control of substantia nigra dopaminergic neurons. Prog. Brain Res. 160:189–208 [Google Scholar]
  99. Jhou TC, Geisler S, Marinelli M, Degarmo BA, Zahm DS. 99.  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]
  100. Johnson SW, North RA. 100.  1992. Two types of neurone in the rat ventral tegmental area and their synaptic inputs. J. Physiol. 450:455–68 [Google Scholar]
  101. Kaufling J, Veinante P, Pawlowski SA, Freund-Mercier MJ, Barrot M. 101.  2009. Afferents to the GABAergic tail of the ventral tegmental area in the rat. J. Comp. Neurol. 513:597–621 [Google Scholar]
  102. Lobb CJ, Wilson CJ, Paladini CA.102.  2010. A dynamic role for GABA receptors on the firing pattern of midbrain dopaminergic neurons. J. Neurophysiol. 104:403–13 [Google Scholar]
  103. Shoji Y, Delfs J, Williams JT. 103.  1999. Presynaptic inhibition of GABAB-mediated synaptic potentials in the ventral tegmental area during morphine withdrawal. J. Neurosci. 19:2347–55 [Google Scholar]
  104. Sugita S, Johnson SW, North RA. 104.  1992. Synaptic inputs to GABAA and GABAB receptors originate from discrete afferent neurons. Neurosci. Lett. 134:207–11 [Google Scholar]
  105. Bocklisch C, Pascoli V, Wong JCY, House DRC, Yvon C. 105.  et al. 2013. Cocaine disinhibits dopamine neurons by potentiation of GABA transmission in the ventral tegmental area. Science 341:1521–25 [Google Scholar]
  106. Chuhma N, Zhang H, Masson J, Zhuang X, Sulzer D. 106.  et al. 2004. Dopamine neurons mediate a fast excitatory signal via their glutamatergic synapses. J. Neurosci. 24:972–81 [Google Scholar]
  107. Edwards NJ, Tejeda HA, Pignatelli M, Zhang S, McDevitt RA. 107.  et al. 2017. Circuit specificity in the inhibitory architecture of the VTA regulates cocaine-induced behavior. Nat. Neurosci. 20:438–48 [Google Scholar]
  108. Xia Y, Driscoll JR, Wilbrecht L, Margolis EB, Fields HL. 108.  et al. 2011. Nucleus accumbens medium spiny neurons target non-dopaminergic neurons in the ventral tegmental area. J. Neurosci. 31:7811–16 [Google Scholar]
  109. Jalabert M, Bourdy R, Courtin J, Veinante P, Manzoni OJ. 109.  et al. 2011. Neuronal circuits underlying acute morphine action on dopamine neurons. PNAS 108:16446–50 [Google Scholar]
  110. Arora D, Hearing M, Haluk DM, Mirkovic K, Fajardo-Serrano A. 110.  et al. 2011. Acute cocaine exposure weakens GABAB receptor-dependent G-protein-gated inwardly rectifying K+ signaling in dopamine neurons of the ventral tegmental area. J. Neurosci. 31:12251–57 [Google Scholar]
  111. Padgett CL, Lalive AL, Tan KR, Terunuma M, Munoz MB. 111.  et al. 2012. Methamphetamine-evoked depression of GABAB receptor signaling in GABA neurons of the VTA. Neuron 73:978–89 [Google Scholar]
  112. Lalive A, Munoz MB, Bellone C, Slesinger PA, Lüscher C. 112.  et al. 2014. Firing modes of dopamine neurons drive bidirectional GIRK channel plasticity. J. Neurosci. 34:5107–14 [Google Scholar]
  113. Creed MC, Ntamati NR, Tan KR. 113.  2014. VTA GABA neurons modulate specific learning behaviors through the control of dopamine and cholinergic systems. Front. Behav. Neurosci. 8:32–38 [Google Scholar]
  114. Tan KR, Yvon C, Turiault M, Mirzabekov JJ, Doehner J. 114.  et al. 2012. GABA neurons of the VTA drive conditioned place aversion. Neuron 73:1173–83 [Google Scholar]
  115. van Zessen R, Phillips JL, Budygin EA, Stuber GD. 115.  2012. Activation of VTA GABA neurons disrupts reward consumption. Neuron 73:1184–94 [Google Scholar]
  116. Cohen JY, Haesler S, Vong L, Lowell BB, Uchida N. 116.  2012. Neuron-type-specific signals for reward and punishment in the ventral tegmental area. Nature 482:85–88 [Google Scholar]
  117. Ungless MA, Magill PJ, Bolam JP. 117.  2004. Uniform inhibition of dopamine neurons in the ventral tegmental area by aversive stimuli. Science 303:2040–42 [Google Scholar]
  118. Morales M, Root DH. 118.  2014. Glutamate neurons within the midbrain dopamine regions. Neuroscience 282:60–68 [Google Scholar]
  119. Yamaguchi T, Qi J, Wang H-L, Zhang S, Morales M. 119.  2015. Glutamatergic and dopaminergic neurons in the mouse ventral tegmental area. Eur. J. Neurosci. 41:760–72 [Google Scholar]
  120. Yamaguchi T, Wang H-L, Li X, Ng TH, Morales M. 120.  2011. Mesocorticolimbic glutamatergic pathway. J. Neurosci. 31:8476–90 [Google Scholar]
  121. Chuhma N, Mingote S, Moore H, Rayport S. 121.  2014. Dopamine neurons control striatal cholinergic neurons via regionally heterogeneous dopamine and glutamate signaling. Neuron 81:901–12 [Google Scholar]
  122. Dal Bo G, St-Gelais F, Danik M, Williams S, Cotton M. 122.  et al. 2004. Dopamine neurons in culture express VGLUT2 explaining their capacity to release glutamate at synapses in addition to dopamine. J. Neurochem. 88:1398–1405 [Google Scholar]
  123. Stuber GD, Hnasko TS, Britt JP, Edwards RH, Bonci A. 123.  2010. Dopaminergic terminals in the nucleus accumbens but not the dorsal striatum corelease glutamate. J. Neurosci. 30:8229–33 [Google Scholar]
  124. Sulzer D, Joyce MP, Lin L, Geldwert D, Haber SN. 124.  et al. 1998. Dopamine neurons make glutamatergic synapses in vitro. . J. Neurosci. 18:4588–602 [Google Scholar]
  125. Tecuapetla F, Patel JC, Xenias H, English D, Tadros I. 125.  et al. 2010. Glutamatergic signaling by mesolimbic dopamine neurons in the nucleus accumbens. J. Neurosci. 30:7105–10 [Google Scholar]
  126. Wang DV, Viereckel T, Zell V, Konradsson-Geuken Å, Broker CJ, Talishinsky A. 126.  et al. 2017. Disrupting glutamate co-transmission does not affect acquisition of conditioned behavior reinforced by dopamine neuron activation. Cell Rep 18:2584–91 [Google Scholar]
  127. Dobi A, Margolis EB, Wang H-L, Harvey BK, Morales M. 127.  2010. Glutamatergic and nonglutamatergic neurons of the ventral tegmental area establish local synaptic contacts with dopaminergic and nondopaminergic neurons. J. Neurosci. 30:218–29 [Google Scholar]
  128. Wang H-L, Qi J, Zhang S, Wang H, Morales M. 128.  2015. Rewarding effects of optical stimulation of ventral tegmental area glutamatergic neurons. J. Neurosci. 35:15948–54 [Google Scholar]
  129. Cui G, Bernier BE, Harnett MT, Morikawa H. 129.  2007. Differential regulation of action potential- and metabotropic glutamate receptor-induced Ca2+ signals by inositol 1,4,5-trisphosphate in dopaminergic neurons. J. Neurosci. 27:4776–85 [Google Scholar]
  130. Morikawa H, Imani F, Khodakhah K, Williams JT. 130.  2000. Inositol 1,4,5-triphosphate-evoked responses in midbrain dopamine neurons. J. Neurosci. 20:RC103 [Google Scholar]
  131. Riegel AC, Williams JT. 131.  2008. CRF facilitates calcium release from intracellular stores in midbrain dopamine neurons. Neuron 57:559–70 [Google Scholar]
  132. Schultz W.132.  1998. Predictive reward signal of dopamine neurons. J. Neurophysiol. 80:1–27 [Google Scholar]
  133. Medina JF, Repa JC, Mauk MD, LeDoux JE. 133.  2002. Parallels between cerebellum- and amygdala-dependent conditioning. Nat. Rev. Neurosci. 3:122–31 [Google Scholar]
  134. Nabavi S, Fox R, Proulx CD, Lin JY, Tsien RY. 134.  et al 2014. Engineering a memory with LTD and LTP. Nature 511:348–52 [Google Scholar]
  135. Suvrathan A, Payne HL, Raymond JL. 135.  2016. Timing rules for synaptic plasticity matched to behavioral function. Neuron 92:959–67 [Google Scholar]
  136. Wang SS, Denk W, Häusser M. 136.  2000. Coincidence detection in single dendritic spines mediated by calcium release. Nat. Neurosci. 3:1266–73 [Google Scholar]
  137. Stauffer WR, Lak A, Yang A, Borel M, Paulsen O. 137.  et al. 2016. Dopamine neuron-specific optogenetic stimulation in rhesus macaques. Cell 166:1564–71 [Google Scholar]
  138. Barker DJ, Root DH, Zhang S, Morales M. 138.  2016. Multiplexed neurochemical signaling by neurons of the ventral tegmental area. J. Chem. Neuroanat. 73:33–42 [Google Scholar]
  139. Lammel S, Lim BK, Malenka RC. 139.  2014. Reward and aversion in a heterogeneous midbrain dopamine system. Neuropharmacology 76:Pt. B351–59 [Google Scholar]
  140. Roeper J.140.  2013. Dissecting the diversity of midbrain dopamine neurons. Trends Neurosci 36:336–42 [Google Scholar]
  141. Trudeau LE, Hnasko TS, Wallen-Mackenzie A, Morales M, Rayport S. 141.  et al. 2014. The multilingual nature of dopamine neurons. Prog. Brain Res. 211:141–64 [Google Scholar]
  142. Xin W, Edwards N, Bonci A. 142.  2016. VTA dopamine neuron plasticity—the unusual suspects. Eur. J. Neurosci. 44:2975–83 [Google Scholar]
  143. Wolf ME.143.  1998. The role of excitatory amino acids in behavioral sensitization to psychomotor stimulants. Prog. Neurobiol. 54:679–720 [Google Scholar]
  144. Robinson TE, Berridge KC. 144.  2003. Addiction. Annu. Rev. Psychol. 54:25–53 [Google Scholar]
  145. Cador M, Bjijou Y, Cailhol S, Stinus L. 145.  1999. D-amphetamine-induced behavioral sensitization: implication of a glutamatergic medial prefrontal cortex-ventral tegmental area innervation. Neuroscience 94:705–21 [Google Scholar]
  146. Kalivas PW, Alesdatter JE. 146.  1993. Involvement of N-methyl-D-aspartate receptor stimulation in the ventral tegmental area and amygdala in behavioral sensitization to cocaine. J. Pharmacol. Exp. Ther. 267:486–95 [Google Scholar]
  147. Bonci A, Malenka RC. 147.  1999. Properties and plasticity of excitatory synapses on dopaminergic and GABAergic cells in the ventral tegmental area. J. Neurosci. 19:3723–30 [Google Scholar]
  148. Overton PG, Richards CD, Berry MS, Clark D. 148.  1999. Long-term potentiation at excitatory amino acid synapses on midbrain dopamine neurons. Neuroreport 10:221–26 [Google Scholar]
  149. Bellone C, Lüscher C. 149.  2005. mGluRs induce a long-term depression in the ventral tegmental area that involves a switch of the subunit composition of AMPA receptors. Eur. J. Neurosci. 21:1280–88 [Google Scholar]
  150. Jones S, Kornblum JL, Kauer JA. 150.  2000. Amphetamine blocks long-term synaptic depression in the ventral tegmental area. J. Neurosci. 20:5575–80 [Google Scholar]
  151. Thomas MJ, Malenka RC, Bonci A. 151.  2000. Modulation of long-term depression by dopamine in the mesolimbic system. J. Neurosci. 20:5581–86 [Google Scholar]
  152. Artola A, Singer W. 152.  1993. Long-term depression of excitatory synaptic transmission and its relationship to long-term potentiation. Trends Neurosci 16:480–87 [Google Scholar]
  153. Mameli M, Balland B, Lujan R, Lüscher C. 153.  2007. Rapid synthesis and synaptic insertion of GluR2 for mGluR-LTD in the ventral tegmental area. Science 317:530–33 [Google Scholar]
  154. Feldman DE.154.  2012. The spike-timing dependence of plasticity. Neuron 75:556–71 [Google Scholar]
  155. Argilli E, Sibley DR, Malenka RC, England PM, Bonci A. 155.  2008. Mechanism and time course of cocaine-induced long-term potentiation in the ventral tegmental area. J. Neurosci. 28:9092–100 [Google Scholar]
  156. Luu P, Malenka RC. 156.  2008. Spike timing-dependent long-term potentiation in ventral tegmental area dopamine cells requires PKC. J. Neurophysiol. 100:533–38 [Google Scholar]
  157. Mameli M, Bellone C, Brown MT, Lüscher C. 157.  2011. Cocaine inverts rules for synaptic plasticity of glutamate transmission in the ventral tegmental area. Nat. Neurosci. 14:414–16 [Google Scholar]
  158. Stuber GD, Klanker M, de Ridder B, Bowers MS, Joosten RN. 158.  et al. 2008. Reward-predictive cues enhance excitatory synaptic strength onto midbrain dopamine neurons. Science 321:1690–92 [Google Scholar]
  159. Zweifel LS, Argilli E, Bonci A, Palmiter RD. 159.  2008. Role of NMDA receptors in dopamine neurons for plasticity and addictive behaviors. Neuron 59:486–96 [Google Scholar]
  160. Bowers MS, Chen BT, Bonci A. 160.  2010. AMPA receptor synaptic plasticity induced by psychostimulants: the past, present, and therapeutic future. Neuron 67:11–24 [Google Scholar]
  161. Creed MC, Lüscher C. 161.  2013. Drug-evoked synaptic plasticity: beyond metaplasticity. Curr. Opin. Neurobiol. 23:553–58 [Google Scholar]
  162. Chen BT, Bowers MS, Martin M, Hopf FW, Guillory AM. 162.  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]
  163. Covey DP, Roitman MF, Garris PA. 163.  2014. Illicit dopamine transients: reconciling actions of abused drugs. Trends Neurosci 37:200–10 [Google Scholar]
  164. Koulchitsky S, De Backer B, Quertemont E, Charlier C, Seutin V. 164.  2012. Differential effects of cocaine on dopamine neuron firing in awake and anesthetized rats. Neuropsychopharmacology 37:1559–71 [Google Scholar]
  165. Sombers LA, Beyene M, Carelli RM, Wightman RM. 165.  2009. Synaptic overflow of dopamine in the nucleus accumbens arises from neuronal activity in the ventral tegmental area. J. Neurosci. 29:1735–42 [Google Scholar]
  166. Stuber GD, Klanker M, de Ridder B, Bowers MS, Joosten RN. 166.  et al. 2008. Reward-predictive cues enhance excitatory synaptic strength onto midbrain dopamine neurons. Science 321:1690–92 [Google Scholar]
  167. Sarti F, Borgland SL, Kharazia VN, Bonci A. 167.  2007. Acute cocaine exposure alters spine density and long-term potentiation in the ventral tegmental area. Eur. J. Neurosci. 26:749–56 [Google Scholar]
  168. Harnett MT, Bernier BE, Ahn KC, Morikawa H. 168.  2009. Burst-timing-dependent plasticity of NMDA receptor-mediated transmission in midbrain dopamine neurons. Neuron 62:826–38 [Google Scholar]
  169. Dore K, Aow J, Malinow R. 169.  2016. The emergence of NMDA receptor metabotropic function: insights from imaging. Front. Synaptic Neurosci. 8:20 [Google Scholar]
  170. Ahn KC, Bernier BE, Harnett MT, Morikawa H. 170.  2010. IP3 receptor sensitization during in vivo amphetamine experience enhances NMDA receptor plasticity in dopamine neurons of the ventral tegmental area. J. Neurosci. 30:6689–99 [Google Scholar]
  171. Stelly CE, Pomrenze MB, Cook JB, Morikawa H. 171.  2016. Repeated social defeat stress enhances glutamatergic synaptic plasticity in the VTA and cocaine place conditioning. eLife 5:e15448 [Google Scholar]
  172. Whitaker LR, Degoulet M, Morikawa H. 172.  2013. Social deprivation enhances VTA synaptic plasticity and drug-induced contextual learning. Neuron 77:335–45 [Google Scholar]
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