Electrophysiological Characteristics of Dopamine Neurons: A 35-Year Update

  • Wei-Xing ShiEmail author
Part of the Journal of Neural Transmission. Supplementa book series (NEURALTRANS, volume 73)


This chapter consists of four sections. The first section provides a general description of the electrophysiological characteristics of dopamine (DA) neurons in both the substantia nigra and ventral tegmental area. Emphasis is placed on the differences between DA and neighboring non-DA neurons. The second section discusses the ionic mechanisms underlying the generation of action potential in DA cells. Evidence is provided to suggest that these mechanisms differ not only between DA and non-DA neurons but also between DA cells located in different areas, with different projection sites and at different developmental stages. Some of the differences may play a critical role in the vulnerability of a DA neuron to cell death. The third section describes the firing patterns of DA cells. Data are presented to show that the current “80/160 ms” criteria for burst identification need to be revised and that the burst firing, originally described by Bunney et al., can be described as slow oscillations in firing rate. In the ventral tegmental area, the slow oscillations are, at least partially, derived from the prefrontal cortex and part of prefrontal information is transferred to DA cells indirectly through inhibitory neurons. The final section focuses on the feedback regulation of DA cells. New evidence suggests that DA autoreceptors are coupled to multiple effectors, and both D1 and D2-like receptors are involved in long-loop feedback control of DA neurons. Because of the presence of multiple feedback and nonfeedback pathways, the effect of a drug on a DA neuron can be far more complex than an inhibition or excitation. A better understanding of the intrinsic properties of DA neurons and their regulation by afferent input will, in time, help to point to the way to more effective and safer treatments for disorders including schizophrenia, drug addiction, and Parkinson’s disease.


Amphetamine Antipsychotic drug A-type K+ channel Autoreceptor Burst Feedback control IH channel Non-DA neurons Pacemaker potential Prefrontal cortex SK channel Slow oscillation Striatum Substantia nigra Ventral tegmental area 













Basolateral amygdale




Cyclic adenosine monophosphate






Gamma-aminobutyric acid


High voltage-activated


Inositol triphosphate


Intermediate conductance calcium-activated K channels


Large conductance calcium-activated K channels


Low voltage-activated


Metabotropic glutamate receptors


Nucleus accumbens


N-methyl-D-aspartic acid


Prefrontal cortex


Protein kinase A


slow oscillations


Small conductance calcium-activated K channels


Substantia nigra


Ventral tegmental area




Transient receptor potential


Tyrosine hydroxylase



This work was supported, in part, by a NARSAD Independent Investigator Award and NIDA DA12944.


  1. Aghajanian GK, Bunney BS (1973) Frontiers in Catecholamine Research. In: Usdin E, Snyder SH (eds) Central dopaminergic neurons: Neurophysiological identification and responses to drugs. Pergamon Press, New York, pp 643–648Google Scholar
  2. Aghajanian GK, Bunney BS (1974) Frontiers of Neurology and Neuroscience Research. In: Seeman P, Brown GM (eds) Pre- and postsynaptic feedback mechanisms in central dopaminergic neurons. University of Toronto Press, Toronto, Ontario, Canada, pp 4–11Google Scholar
  3. Aghajanian GK, Bunney BS (1977a) Pharmacological characterization of dopamine "autoreceptors" by microiontophoretic single-cell recording studies. Adv Biochem Psychopharmacol 16:433–438PubMedGoogle Scholar
  4. Aghajanian GK, Bunney BS (1977b) Dopamine“autoreceptors”: pharmacological characterization by microiontophoretic single cell recording studies. Naunyn Schmiedebergs Arch Pharmacol 297:1–7PubMedCrossRefGoogle Scholar
  5. Arencibia-Albite F, Paladini C, Williams JT, Jimenez-Rivera CA (2007) Noradrenergic modulation of the hyperpolarization- activated cation current (Ih) in dopamine neurons of the ventral tegmental area. Neuroscience 149:303–314PubMedCrossRefGoogle Scholar
  6. Atherton JF, Bevan MD (2005) Ionic mechanisms underlying autonomous action potential generation in the somata and dendrites of GABAergic substantia nigra pars reticulata neurons in vitro. J Neurosci 25:8272–8281PubMedCrossRefGoogle Scholar
  7. Beckstead MJ, Grandy DK, Wickman K, Williams JT (2004) Vesicular dopamine release elicits an inhibitory postsynaptic current in midbrain dopamine neurons. Neuron 42:939–946PubMedCrossRefGoogle Scholar
  8. Bergquist F, Nissbrandt H (2003) Influence of r-type (Cav2.3) and t-type (Cav3.1–3.3) antagonists on nigral somatodendritic dopamine release measured by microdialysis. Neuroscience 120: 757–764PubMedCrossRefGoogle Scholar
  9. Bergstrom DA, Walters JR (1981) Neuronal responses of the globus pallidus to systemic administration of d-amphetamine: investigation of the involvement of dopamine, norepinephrine, and serotonin. J Neurosci 1:292–299PubMedGoogle Scholar
  10. Bergstrom DA, Bromley SD, Walters JR (1984) Dopamine agonists increase pallidal unit activity: attenuation by agonist pretreatment and anesthesia. Eur J Pharmacol 100:3–12PubMedCrossRefGoogle Scholar
  11. Bertorello AM, Hopfield JF, Aperia A, Greengard P (1990) Inhibition by dopamine of (Na(+)+K+) ATPase activity in neostriatal neurons through D1 and D2 dopamine receptor synergism. Nature 347: 386–388PubMedCrossRefGoogle Scholar
  12. Blythe SN, Atherton JF, Bevan MD (2007) Synaptic activation of dendritic AMPA and NMDA receptors generates transient high-frequency firing in substantia nigra dopamine neurons in vitro. J Neurophysiol 97:2837–2850PubMedCrossRefGoogle Scholar
  13. Bordi F, Meller E (1989) Enhanced behavioral stereotypies elicited by intrastriatal injection D1 and D2 dopamine agonists in intact rats. Brain Res 504:276–283PubMedCrossRefGoogle Scholar
  14. Bouthenet ML, Souil E, Martres MP, Sokoloff P, Giros B, Schwartz JC (1991) Localization of dopamine D3 receptor mRNA in the rat brain using in situ hybridization histochemistry: comparison with dopamine D2 receptor mRNA. Brain Res 564:203–219PubMedCrossRefGoogle Scholar
  15. Bunney BS, Aghajanian GK (1975) Evidence for drug actions on both pre- and postsynaptic catecholamine receptors in the CNS. Psychopharmacol Bull 11:8–10PubMedGoogle Scholar
  16. Bunney BS, Achajanian GK (1976) d-Amphetamine-induced inhibition of central dopaminergic neurons: mediation by a striato-nigral feedback pathway. Science 192:391–393PubMedCrossRefGoogle Scholar
  17. Bunney BS, Aghajanian GK (1977) D-Amphetamine-induced inhibition of central dopaminergic neurons: direct effect or mediated by a striatonigral feedback pathway? Adv Biochem Psychopharmacol 16:577–582PubMedGoogle Scholar
  18. Bunney BS, Aghajanian GK (1978) d-Amphetamine-induced depression of central dopamine neurons: evidence for mediation by both autoreceptors and a striato-nigral feedback pathway. Naunyn Schmiedebergs Arch Pharmacol 304:255–261PubMedCrossRefGoogle Scholar
  19. Bunney BS, Aghajanian GK, Roth RH (1973a) Comparison of effects of L-dopa, amphetamine and apomorphine on firing rate of rat dopaminergic neurones. Nat New Biol 245:123–125PubMedGoogle Scholar
  20. Bunney BS, Walters JR, Roth RH, Aghajanian GK (1973b) Dopaminergic neurons: effect of antipsychotic drugs and amphetamine on single cell activity. J Pharmacol Exp Ther 185:560–571PubMedGoogle Scholar
  21. Caputi L, Hainsworth A, Guatteo E, Tozzi A, Stefani A, Spadoni F, Leach M, Bernardi G, Mercuri NB (2003) Actions of the sodium channel inhibitor 202W92 on rat midbrain dopaminergic neurons. Synapse 48:123–130PubMedCrossRefGoogle Scholar
  22. Cardozo DL, Bean BP (1995) Voltage-dependent calcium channels in rat midbrain dopamine neurons: modulation by dopamine and GABAB receptors. J Neurophysiol 74:1137–1148PubMedGoogle Scholar
  23. Carlson JH, Bergstrom DA, Walters JR (1986) Neurophysiological evidence that D-1 dopamine receptor blockade attenuates postsynaptic but not autoreceptor-mediated effects of dopamine agonists. Eur J Pharmacol 123:237–251PubMedCrossRefGoogle Scholar
  24. Carlson JH, Bergstrom DA, Weick BG, Walters JR (1987) Neurophysiological investigation of effects of the D-1 agonist SKF 38393 on tonic activity of substantia nigra dopamine neurons. Synapse 1:411–416PubMedCrossRefGoogle Scholar
  25. Cathala L, Paupardin-Tritsch D (1999) Effect of catecholamines on the hyperpolarization-activated cationic Ih and the inwardly rectifying potassium I(Kir) currents in the rat substantia nigra pars compacta. Eur J Neurosci 11:398–406PubMedCrossRefGoogle Scholar
  26. Centonze D, Usiello A, Gubellini P, Pisani A, Borrelli E, Bernardi G, Calabresi P (2002) Dopamine D2 receptor-mediated inhibition of dopaminergic neurons in mice lacking D2L receptors. Neuropsychopharmacology 27:723–726PubMedCrossRefGoogle Scholar
  27. Chan CS, Guzman JN, Ilijic E, Mercer JN, Rick C, Tkatch T, Meredith GE, Surmeier DJ (2007) 'Rejuvenation' protects neurons in mouse models of Parkinson's disease. Nature 447:1081–1086PubMedCrossRefGoogle Scholar
  28. Chen BT, Moran KA, Avshalumov MV, Rice ME (2006) Limited regulation of somatodendritic dopamine release by voltage-sensitive Ca2+ channels contrasted with strong regulation of axonal dopamine release. J Neurochem 96:645–655PubMedCrossRefGoogle Scholar
  29. Chiodo LA, Bannon MJ, Grace AA, Roth RH, and Bunney BS (1984) Evidence for the absence of impulse-regulating somatodendritic and synthesis-modulating nerve terminal autoreceptors on subpopulations of mesocortical dopamine neurons. Neuroscience 12: 1–16Google Scholar
  30. Cui G, Okamoto T, Morikawa H (2004) Spontaneous opening of T-type Ca2+ channels contributes to the irregular firing of dopamine neurons in neonatal rats. J Neurosci 24:11079–11087PubMedCrossRefGoogle Scholar
  31. Cui G, Bernier BE, Harnett MT, Morikawa H (2007) Differential regulation of action potential- and metabotropic glutamate receptor-induced Ca2+ signals by inositol 1, 4, 5-trisphosphate in dopaminergic neurons. J Neurosci 27:4776–4785PubMedCrossRefGoogle Scholar
  32. Davila V, Yan Z, Craciun LC, Logothetis D, Sulzer D (2003) D3 dopamine Autoreceptors Do Not Activate G-protein-Gated Inwardly rectifying potassium channel currents in substantia nigra dopamine neurons. J Neurosci 23:5693–5697PubMedGoogle Scholar
  33. Diaz J, Pilon C, Le Foll B, Gros C, Triller A, Schwartz J-C, Sokoloff P (2000) Dopamine D3 receptors expressed by all mesencephalic dopamine neurons. J Neurosci 20:8677–8684PubMedGoogle Scholar
  34. Durante P, Cardenas CG, Whittaker JA, Kitai ST, Scroggs RS (2004) Low-threshold L-type calcium channels in rat dopamine neurons. J Neurophysiol 91:1450–1454PubMedCrossRefGoogle Scholar
  35. Einhorn LC, Johansen PA, White FJ (1988) Electrophysiological effects of cocaine in the mesoaccumbens dopamine system: studies in the ventral tegmental area. J Neurosci 8:100–112PubMedGoogle Scholar
  36. Fiorillo CD, Williams JT (1998) Glutamate mediates an inhibitory postsynaptic potential in dopamine neurons. Nature 394: 78–82PubMedCrossRefGoogle Scholar
  37. Ford CP, Mark GP, Williams JT (2006) Properties and opioid inhibition of mesolimbic dopamine neurons vary according to target location. J Neurosci 26:2788–2797PubMedCrossRefGoogle Scholar
  38. Franz O, Liss B, Neu A, Roeper J (2000) Single-cell mRNA expression of HCN1 correlates with a fast gating phenotype of hyperpolarization-activated cyclic nucleotide-gated ion channels (Ih) in central neurons. Eur J Neurosci 12:2685–2693PubMedCrossRefGoogle Scholar
  39. Fujimura K, Matsuda Y (1989) Autogenous oscillatory potentials in neurons of the guinea pig substantia nigra pars compacta in vitro. Neurosci Lett 104:53–57PubMedCrossRefGoogle Scholar
  40. Gao M, Liu CL, Yang S, Jin GZ, Bunney BS, Shi WX (2007) Functional coupling between the prefrontal cortex and dopamine neurons in the ventral tegmental area. J Neurosci 27:5414–5421PubMedCrossRefGoogle Scholar
  41. Gariano RF, Sawyer SF, Tepper JM, Young SJ, Groves PM (1989a) Mesocortical dopaminergic neurons. 2. Electrophysiological consequences of terminal autoreceptor activation. Brain Res Bull 22:517–523PubMedCrossRefGoogle Scholar
  42. Gariano RF, Tepper JM, Sawyer SF, Young SJ, Groves PM (1989b) Mesocortical dopaminergic neurons. 1. Electrophysiological properties and evidence for soma-dendritic autoreceptors. Brain Res Bull 22:511–516PubMedCrossRefGoogle Scholar
  43. Gentet LJ, Williams SR (2007) Dopamine gates action potential backpropagation in midbrain dopaminergic neurons. J Neurosci 27:1892–1901PubMedCrossRefGoogle Scholar
  44. Gerfen CR (1984) The neostriatal mosaic: compartmentalization of corticostriatal input and striatonigral output systems. Nature 311:461–464PubMedCrossRefGoogle Scholar
  45. Gerfen CR (1985) The neostriatal mosaic. I. Compartmental organization of projections from the striatum to the substantia nigra in the rat. J Comp Neurol 236:454–476PubMedCrossRefGoogle Scholar
  46. Grace AA (1990) Evidence for the functional compartmentalization of spike generating regions of rat midbrain dopamine neurons recorded in vitro. Brain Res 524:31–41PubMedCrossRefGoogle Scholar
  47. Grace AA, Bunney BS (1980) Nigral dopamine neurons: intracellular recording and identification with L-dopa injection and histofluorescence. Science 210:654–656PubMedCrossRefGoogle Scholar
  48. Grace AA, Bunney BS (1983) Intracellular and extracellular electrophysiology of nigral dopaminergic neurons–1. Identification and characterization. Neuroscience 10:301–315PubMedCrossRefGoogle Scholar
  49. Grace AA, Bunney BS (1984) The control of firing pattern in nigral dopamine neurons: burst firing. J Neurosci 4:2877–2890PubMedGoogle Scholar
  50. Grace AA, Bunney BS (1985) Low doses of apomorphine elicit two opposing influences on dopamine cell electrophysiology. Brain Res 333:285–298PubMedCrossRefGoogle Scholar
  51. Grace AA, Onn SP (1989) Morphology and electrophysiological properties of immunocytochemically identified rat dopamine neurons recorded in vitro. J Neurosci 9:3463–3481PubMedGoogle Scholar
  52. Guyenet PG, Aghajanian GK (1978) Antidromic identification of dopaminergic and other output neurons of the rat substantia nigra. Brain Res 150:69–84PubMedCrossRefGoogle Scholar
  53. Hahn J, Tse TE, Levitan ES (2003) Long-term K+ channel-mediated dampening of dopamine neuron excitability by the antipsychotic drug haloperidol. J Neurosci 23:10859–10866PubMedGoogle Scholar
  54. Hahn J, Kullmann PH, Horn JP, Levitan ES (2006) D2 autoreceptors chronically enhance dopamine neuron pacemaker activity. J Neurosci 26:5240–5247PubMedCrossRefGoogle Scholar
  55. Harris NC (1992) Sensitivity of transient outward rectification to ion channel blocking agents in guinea-pig substantia nigra pars compacta neurones in vitro. Brain Res 596:325–329PubMedCrossRefGoogle Scholar
  56. Harris NC, Webb C, Greenfield SA (1989) A possible pacemaker mechanism in pars compacta neurons of the guinea-pig substantia nigra revealed by various ion channel blocking agents. Neuroscience 31:355–362PubMedCrossRefGoogle Scholar
  57. Hausser M, Stuart G, Racca C, Sakmann B (1995) Axonal initiation and active dendritic propagation of action potentials in substantia nigra neurons. Neuron 15:637–647PubMedCrossRefGoogle Scholar
  58. Huang KX, Walters JR (1992) D1 receptor stimulation inhibits dopamine cell activity after reserpine treatment but not after chronic SCH 23390: an effect blocked by N-methyl-D-aspartate antagonists. J Pharmacol Exp Ther 260:409–416PubMedGoogle Scholar
  59. Hyland BI, Reynolds JN, Hay J, Perk CG, Miller R (2002) Firing modes of midbrain dopamine cells in the freely moving rat. Neuroscience 114:475–492CrossRefGoogle Scholar
  60. Innis RB, Aghajanian GK (1987) Pertussis toxin blocks autoreceptor-mediated inhibition of dopaminergic neurons in rat substantia nigra. Brain Res 411:139–143PubMedCrossRefGoogle Scholar
  61. Ishiwa D, Nagata I, Ohtsuka T, Itoh H, Kamiya Y, Ogawa K, Sakai M, Sekino N, Yamada Y, Goto T, Andoh T (2008) Differential effects of isoflurane on A-type and delayed rectifier K channels in rat substantia nigra. Eur J Pharmacol 580:122–129PubMedCrossRefGoogle Scholar
  62. Ji H, Shepard PD (2006) SK Ca2+-activated K+ channel ligands alter the firing pattern of dopamine-containing neurons in vivo. Neuroscience 140:623–633PubMedCrossRefGoogle Scholar
  63. Johnson SW, North RA (1992) Two types of neurone in the rat ventral tegmental area and their synaptic inputs. J Physiol 450:455–468PubMedGoogle Scholar
  64. Johnson SW, Seutin V, North RA (1992) Burst firing in dopamine neurons induced by N-methyl-D-aspartate: role of electrogenic sodium pump. Science 258:665–667PubMedCrossRefGoogle Scholar
  65. Kalivas PW, Duffy P (1991) A comparison of axonal and somatodendritic dopamine release using in vivo dialysis. J Neurochem 56:961–967PubMedCrossRefGoogle Scholar
  66. Kamata K, Rebec GV (1983) Dopaminergic and neostriatal neurons: dose-dependent changes in sensitivity to amphetamine following long-term treatment. Neuropharmacology 22:1377–1382PubMedCrossRefGoogle Scholar
  67. Kang Y, Kitai ST (1993a) A whole cell patch-clamp study on the pacemaker potential in dopaminergic neurons of rat substantia nigra compacta. Neurosci Res 18:209–221PubMedCrossRefGoogle Scholar
  68. Kang Y, Kitai ST (1993b) Calcium spike underlying rhythmic firing in dopaminergic neurons of the rat substantia nigra. Neurosci Res 18:195–207PubMedCrossRefGoogle Scholar
  69. Katayama J, Akaike N, Nabekura J (2003) Characterization of pre- and post-synaptic metabotropic glutamate receptor-mediated inhibitory responses in substantia nigra dopamine neurons. Neurosci Res 45:101–115PubMedCrossRefGoogle Scholar
  70. Kelland MD, Freeman AS, Chiodo LA (1988) SKF 38393 alters the rate-dependent D2-mediated inhibition of nigrostriatal but not mesoaccumbens dopamine neurons. Synapse 2:416–423CrossRefGoogle Scholar
  71. Kelland MD, Freeman AS, Chiodo LA (1989) Chloral hydrate anesthesia alters the responsiveness of identified midbrain dopamine neurons to dopamine agonist administration. Synapse 3:30–37CrossRefGoogle Scholar
  72. Kim SH, Choi YM, Jang JY, Chung S, Kang YK, Park MK (2007) Nonselective cation channels are essential for maintaining intracellular Ca2+ levels and spontaneous firing activity in the midbrain dopamine neurons. Pflugers Arch 455:309–321PubMedCrossRefGoogle Scholar
  73. Kita T, Kita H, Kitai ST (1986) Electrical membrane properties of rat substantia nigra compacta neurons in an in vitro slice preparation. Brain Res 372:21–30PubMedCrossRefGoogle Scholar
  74. Kitai ST, Shepard PD, Callaway JC, Scroggs R (1999) Afferent modulation of dopamine neuron firing patterns. Curr Opin Neurobiol 9:690–697PubMedCrossRefGoogle Scholar
  75. Koeltzow TE, Xu M, Cooper DC, Hu XT, Tonegawa S, Wolf ME, White FJ (1998) Alterations in dopamine release but not dopamine autoreceptor function in dopamine D3 receptor mutant mice. J Neurosci 18:2231–2238PubMedGoogle Scholar
  76. Koyama S, Appel SB (2006a) Characterization of M-current in ventral tegmental area dopamine neurons. J Neurophysiol 96: 535–543PubMedCrossRefGoogle Scholar
  77. Koyama S, Appel SB (2006b) A-type K+ current of dopamine and GABA neurons in the ventral tegmental area. J Neurophysiol 96:544–554PubMedCrossRefGoogle Scholar
  78. Koyama S, Kanemitsu Y, Weight FF (2005) Spontaneous activity and properties of two types of principal neurons from the ventral tegmental area of rat. J Neurophysiol 93:3282–3293PubMedCrossRefGoogle Scholar
  79. Kreiss DS, Bergstrom DA, Gonzalez AM, Huang KX, Sibley DR, Walters JR (1995) Dopamine receptor agonist potencies for inhibition of cell firing correlate with dopamine D3 receptor binding affinities. Eur J Pharmacol 277:209–214PubMedCrossRefGoogle Scholar
  80. Lacey MG, Mercuri NB, North RA (1987) Dopamine acts on D2 receptors to increase potassium conductance in neurones of the rat substantia nigra zona compacta. J Physiol 392:397–416PubMedGoogle Scholar
  81. Lacey MG, Mercuri NB, North RA (1988) On the potassium conductance increase activated by GABAB and dopamine D2 receptors in rat substantia nigra neurones. J Physiol 401:437–453PubMedGoogle Scholar
  82. Lacey MG, Mercuri NB, North RA (1989) Two cell types in rat substantia nigra zona compacta distinguished by membrane properties and the actions of dopamine and opioids. J Neurosci 9: 1233–1241PubMedGoogle Scholar
  83. Lammel S, Hetzel A, Hackel O, Jones I, Liss B, Roeper J (2008) Unique properties of mesoprefrontal neurons within a dual mesocorticolimbic dopamine system. Neuron 57:760–773PubMedCrossRefGoogle Scholar
  84. Lee CR, Tepper JM (2007) Morphological and physiological properties of parvalbumin- and calretinin-containing gamma-aminobutyric acidergic neurons in the substantia nigra. J Comp Neurol 500:958–972PubMedCrossRefGoogle Scholar
  85. Lejeune F, Millan MJ (1995) Activation of dopamine D3 autoreceptors inhibits firing of ventral tegmental dopaminergic neurones in vivo. Eur J Pharmacol 275:R7–9PubMedCrossRefGoogle Scholar
  86. Leysen J, Gommeren W, Mertens J, Luyten W, Pauwels P, Ewert M, Seeburg P (1993) Comparison of in vitro binding properties of a series of dopamine antagonists and agonists for cloned human dopamine D2S and D2L receptors and for D2 receptors in rat striatal and mesolimbic tissues, using [125I] 2′-iodospiperone. Psychopharmacology (Berl) 110:27–36CrossRefGoogle Scholar
  87. Liss B, Franz O, Sewing S, Bruns R, Neuhoff H, Roeper J (2001) Tuning pacemaker frequency of individual dopaminergic neurons by Kv4.3L and KChip3.1 transcription. EMBO J 20: 5715–5724PubMedCrossRefGoogle Scholar
  88. Liu Y, Dore J, Chen X (2007) Calcium influx through L-type channels generates protein kinase M to induce burst firing of dopamine cells in the rat ventral tegmental area. J Biol Chem 282:8594–8603PubMedCrossRefGoogle Scholar
  89. Lu XY, Churchill L, Kalivas PW (1997) Expression of D1 receptor mRNA in projections from the forebrain to the ventral tegmental area. Synapse 25:205–214PubMedCrossRefGoogle Scholar
  90. Lu XY, Ghasemzadeh MB, Kalivas PW (1998) Expression of D1 receptor, D2 receptor, substance P and enkephalin messenger RNAs in the neurons projecting from the nucleus accumbens. Neuroscience 82:767–780PubMedCrossRefGoogle Scholar
  91. Luo AH, Georges FE, Aston-Jones GS (2008) Novel neurons in ventral tegmental area fire selectively during the active phase of the diurnal cycle. Eur J Neurosci 27:408–422PubMedCrossRefGoogle Scholar
  92. Margolis EB, Lock H, Hjelmstad GO, Fields HL (2006) The ventral tegmental area revisited: is there an electrophysiological marker for dopaminergic neurons? J Physiol 577:907–924PubMedCrossRefGoogle Scholar
  93. Meador-Woodruff JH, Mansour A (1991) A. E. Bennett Award paper. Expression of the dopamine D2 receptor gene in brain. Biol Psychiatry 30:985–1007PubMedCrossRefGoogle Scholar
  94. Mercuri NB, Bonci A, Calabresi P, Stefani A, Bernardi G (1995) Properties of the hyperpolarization-activated cation current Ih in rat midbrain dopaminergic neurons. Eur J Neurosci 7:462–469PubMedCrossRefGoogle Scholar
  95. Mercuri NB, Bonci A, Calabresi P, Stratta F, Stefani A, Bernardi G (1994) Effects of dihydropyridine calcium antagonists on rat midbrain dopaminergic neurones. Br J Pharmacol 113:831–838PubMedGoogle Scholar
  96. Mercuri NB, Saiardi A, Bonci A, Picetti R, Calabresi P, Bernardi G, Borrelli E (1997) Loss of autoreceptor function in dopaminergic neurons from dopamine D2 receptor deficient mice. Neuroscience 79:323–327PubMedCrossRefGoogle Scholar
  97. Mereu G, Collu M, Ongini E, Biggio G, Gessa GL (1985) SCH 23390, a selective dopamine D1 antagonist, activates dopamine neurons but fails to prevent their inhibition by apomorphine. Eur J Pharmacol 111:393–396PubMedCrossRefGoogle Scholar
  98. Morikawa H, Khodakhah K, Williams JT (2003) Two intracellular pathways mediate metabotropic glutamate receptor-induced Ca2+ mobilization in dopamine neurons. J Neurosci 23:149–157PubMedGoogle Scholar
  99. Morikawa H, Imani F, Khodakhah K, Williams JT (2000) Inositol 1,4,5-triphosphate-evoked responses in midbrain dopamine neurons. J Neurosci 20:RC103PubMedGoogle Scholar
  100. Nakanishi H, Kita H, Kitai ST (1987) Intracellular study of rat substantia nigra pars reticulata neurons in an in vitro slice preparation: electrical membrane properties and response characteristics to subthalamic stimulation. Brain Res 437:45–55PubMedCrossRefGoogle Scholar
  101. Napier TC, Givens BS, Schulz DW, Bunney BS, Breese GR, Mailman RB (1986) SCH23390 effects on apomorphine-induced responses of nigral dopaminergic neurons. J Pharmacol Exp Ther 236: 838–845PubMedGoogle Scholar
  102. Nedergaard S (1999) Regulation of action potential size and excitability in substantia nigra compacta neurons: sensitivity to 4-aminopyridine. J Neurophysiol 82:2903–2913PubMedGoogle Scholar
  103. Nedergaard S (2004) A Ca2+-independent slow afterhyperpolarization in substantia nigra compacta neurons. Neuroscience 125:841–852PubMedCrossRefGoogle Scholar
  104. Nedergaard S, Greenfield SA (1992) Sub-populations of pars compacta neurons in the substantia nigra: the significance of qualitatively and quantitatively distinct conductances. Neuroscience 48: 423–437PubMedCrossRefGoogle Scholar
  105. Nedergaard S, Flatman JA, Engberg I (1993) Nifedipine- and omega-conotoxin-sensitive Ca2+ conductances in guinea-pig substantia nigra pars compacta neurones. J Physiol 466:727–747PubMedGoogle Scholar
  106. Neuhoff H, Neu A, Liss B, Roeper J (2002) I(h) channels contribute to the different functional properties of identified dopaminergic subpopulations in the midbrain. J Neurosci 22:1290–1302PubMedGoogle Scholar
  107. Piercey MF, Hoffmann WE, Smith MW, Hyslop DK (1996) Inhibition of dopamine neuron firing by pramipexole, a dopamine D3 receptor-preferring agonist: comparison to other dopamine receptor agonists. Eur J Pharmacol 312:35–44PubMedCrossRefGoogle Scholar
  108. Ping HX, Shepard PD (1996) Apamin-sensitive Ca(2+)-activated K+ channels regulate pacemaker activity in nigral dopamine neurons. Neuroreport 7:809–814PubMedCrossRefGoogle Scholar
  109. Pinnock RD (1984) The actions of antipsychotic drugs on dopamine receptors in the rat substantia nigra. Br J Pharmacol 81:631–635PubMedGoogle Scholar
  110. Pinnock RD (1985) Neurotensin depolarizes substantia nigra dopamine neurones. Brain Res 338:151–154PubMedCrossRefGoogle Scholar
  111. Prisco S, Natoli S, Bernardi G, Mercuri NB (2002) Group I metabotropic glutamate receptors activate burst firing in rat midbrain dopaminergic neurons. Neuropharmacology 42:289–296PubMedCrossRefGoogle Scholar
  112. Puopolo M, Raviola E, Bean BP (2007) Roles of subthreshold calcium current and sodium current in spontaneous firing of mouse midbrain dopamine neurons. J Neurosci 27:645–656PubMedCrossRefGoogle Scholar
  113. Richards CD, Shiroyama T, Kitai ST (1997) Electrophysiological and immunocytochemical characterization of GABA and dopamine neurons in the substantia nigra of the rat. Neuroscience 80:545–557PubMedCrossRefGoogle Scholar
  114. Robinson S, Smith DM, Mizumori SJY, Palmiter RD (2004) From the cover: firing properties of dopamine neurons in freely moving dopamine-deficient mice: Effects of dopamine receptor activation and anesthesia. Proc Natl Acad Sci USA 101:13329–13334PubMedCrossRefGoogle Scholar
  115. Sanghera MK, Trulson ME, German DC (1984) Electrophysiological properties of mouse dopamine neurons: in vivo and in vitro studies. Neuroscience 12:793–801PubMedCrossRefGoogle Scholar
  116. Sarpal D, Koenig JI, Adelman JP, Brady D, Prendeville LC, Shepard PD (2004) Regional distribution of SK3 mRNA-containing neurons in the adult and adolescent rat ventral midbrain and their relationship to dopamine-containing cells. Synapse 53:104–113PubMedCrossRefGoogle Scholar
  117. Scroggs RS, Cardenas CG, Whittaker JA, Kitai ST (2001) Muscarine reduces calcium-dependent electrical activity in substantia nigra dopaminergic neurons. J Neurophysiol 86:2966–2972PubMedGoogle Scholar
  118. Segev D, Korngreen A (2007) Kinetics of two voltage-gated K+ conductances in substantia nigra dopaminergic neurons. Brain Res 1173:27–35PubMedCrossRefGoogle Scholar
  119. Serodio P, Rudy B (1998) Differential expression of Kv4 K+ channel subunits mediating subthreshold transient K+ (A-type) currents in rat brain. J Neurophysiol 79:1081–1091PubMedGoogle Scholar
  120. Seutin V, Massotte L, Scuvee-Moreau J, Dresse A (1998) Spontaneous apamin-sensitive hyperpolarizations in dopaminergic neurons of neonatal rats. J Neurophysiol 80:3361–3364PubMedGoogle Scholar
  121. Seutin V, Mkahli F, Massotte L, Dresse A (2000) Calcium release from internal stores is required for the generation of spontaneous hyperpolarizations in dopaminergic neurons of neonatal rats. J Neurophysiol 83:192–197PubMedGoogle Scholar
  122. Seutin V, Massotte L, Renette MF, Dresse A (2001) Evidence for a modulatory role of Ih on the firing of a subgroup of midbrain dopamine neurons. Neuroreport 12:255–258PubMedCrossRefGoogle Scholar
  123. Shepard PD, German DC (1984) A subpopulation of mesocortical dopamine neurons possesses autoreceptors. Eur J Pharmacol 98:455–456PubMedCrossRefGoogle Scholar
  124. Shepard PD, Bunney BS (1988) Effects of apamin on the discharge properties of putative dopamine-containing neurons in vitro. Brain Res 463:380–384PubMedCrossRefGoogle Scholar
  125. Shepard PD, Bunney BS (1991) Repetitive firing properties of putative dopamine-containing neurons in vitro: regulation by an apamin-sensitive Ca(2+)-activated K+ conductance. Exp Brain Res 86:141–150PubMedCrossRefGoogle Scholar
  126. Shepard PD, Canavier CC, Levitan ES (2007) Ether-a-go-go related gene potassium channels: what's all the buzz about? Schizophr Bull 33:1263–1269PubMedCrossRefGoogle Scholar
  127. Shi WX (2005) Slow oscillatory firing: a major firing pattern of dopamine neurons in the ventral tegmental area. J Neurophysiol 94:3516–3522PubMedCrossRefGoogle Scholar
  128. Shi WX, Pun CL, Zhou Y (2004) Psychostimulants induce low- frequency oscillations in the firing activity of dopamine neurons. Neuropsychopharmacology 29:2160–2167PubMedCrossRefGoogle Scholar
  129. Shi WX, Pun CL, Smith PL, Bunney BS (2000a) Endogenous DA-mediated feedback inhibition of DA neurons: involvement of both D(1)- and D(2)-like receptors. Synapse 35:111–119PubMedCrossRefGoogle Scholar
  130. Shi WX, Zhang XY, Pun CL, Bunney BS (2007) Clozapine blocks D-amphetamine-induced excitation of dopamine neurons in the ventral tegmental area. Neuropsychopharmacology 32:1922–1928PubMedCrossRefGoogle Scholar
  131. Shi WX, Smith PL, Pun CL, Millet B, Bunney BS (1997) D1–D2 interaction in feedback control of midbrain dopamine neurons. J Neurosci 17:7988–7994PubMedGoogle Scholar
  132. Shi WX, Pun CL, Zhang XX, Jones MD, Bunney BS (2000b) Dual effects of D-amphetamine on dopamine neurons mediated by dopamine and nondopamine receptors. J Neurosci 20:3504–3511PubMedGoogle Scholar
  133. Silva NL, Bunney BS (1988) Intracellular studies of dopamine neurons in vitro: pacemakers modulated by dopamine. Eur J Pharmacol 149:307–315PubMedCrossRefGoogle Scholar
  134. Skirboll LR, Grace AA, Bunney BS (1979) Dopamine auto- and postsynaptic receptors: electrophysiological evidence for differential sensitivity to dopamine agonists. Science 206:80–82PubMedCrossRefGoogle Scholar
  135. Stanford IM, Lacey MG (1996) Electrophysiological investigation of adenosine trisphosphate-sensitive potassium channels in the rat substantia nigra pars reticulata. Neuroscience 74:499–509PubMedCrossRefGoogle Scholar
  136. Takada M, Kang Y, Imanishi M (2001) Immunohistochemical localization of voltage-gated calcium channels in substantia nigra dopamine neurons. Eur J Neurosci 13:757–762PubMedCrossRefGoogle Scholar
  137. Ugedo L, Grenhoff J, Svensson TH (1988) Effects of nimodipine on the physiological activity of A10-DA neurons. Acta Physiol Scand:33Google Scholar
  138. Ungless MA, Magill PJ, Bolam JP (2004) Uniform inhibition of dopamine neurons in the ventral tegmental area by aversive stimuli. Science 303:2040–2042PubMedCrossRefGoogle Scholar
  139. Vandecasteele M, Glowinski J, Deniau JM, Venance L (2008) Chemical transmission between dopaminergic neuron pairs. Proc Natl Acad Sci USA 105:4904–4909PubMedCrossRefGoogle Scholar
  140. Wachtel SR, Hu XT, Galloway MP, White FJ (1989) D1 dopamine receptor stimulation enables the postsynaptic, but not autoreceptor, effects of D2 dopamine agonists in nigrostriatal and mesoaccumbens dopamine systems. Synapse 4:327–346PubMedCrossRefGoogle Scholar
  141. Walsh JP, Cepeda C, Buchwald NA, Levine MS (1991) Neurophysiological maturation of cat substantia nigra neurons: evidence from in vitro studies. Synapse 7:291–300PubMedCrossRefGoogle Scholar
  142. Walters JR, Bergstrom DA, Carlson JH, Chase TN, Braun AR (1987) D1 dopamine receptor activation required for postsynaptic expression of D2 agonist effects. Science 236:719–722PubMedCrossRefGoogle Scholar
  143. Washio H, Takigachi-Hayashi K, Konishi S (1999) Early postnatal development of substantia nigra neurons in rat midbrain slices: hyperpolarization-activated inward current and dopamine-activated current. Neurosci Res 34:91–101PubMedCrossRefGoogle Scholar
  144. Watts AE, Williams JT, Henderson G (1996) Baclofen inhibition of the hyperpolarization-activated cation current, Ih, in rat substantia nigra zona compacta neurons may be secondary to potassium current activation. J Neurophysiol 76:2262–2270PubMedGoogle Scholar
  145. White FJ (1987) D-1 dopamine receptor stimulation enables the inhibition of nucleus accumbens neurons by a D-2 receptor agonist. Eur J Pharmacol 135:101–105PubMedCrossRefGoogle Scholar
  146. Wilson CJ, Callaway JC (2000) Coupled oscillator model of the dopaminergic neuron of the substantia nigra. Journal of neurophysiology 83:3084–3100Google Scholar
  147. Wicke K, Garcia-Ladona J (2001) The dopamine D3 receptor partial agonist, BP 897, is an antagonist at human dopamine D3 receptors and at rat somatodendritic dopamine D3 receptors. Eur J Pharmacol 424:85–90PubMedCrossRefGoogle Scholar
  148. Wolfart J, Roeper J (2002) Selective coupling of t-type calcium channels to sk potassium channels prevents intrinsic bursting in dopaminergic midbrain neurons. J Neurosci 22:3404–3413PubMedGoogle Scholar
  149. Wolfart J, Neuhoff H, Franz O, Roeper J (2001) Differential expression of the small-conductance, calcium-activated potassium channel SK3 is critical for pacemaker control in dopaminergic midbrain neurons. J Neurosci 21:3443–3456PubMedGoogle Scholar
  150. Yanovsky Y, Zhang W, Misgeld U (2005) Two pathways for the activation of small-conductance potassium channels in neurons of substantia nigra pars reticulata. Neuroscience 136:1027–1036PubMedCrossRefGoogle Scholar
  151. Yung KK, Bolam JP, Smith AD, Hersch SM, Ciliax BJ, Levey AI (1995) Immunocytochemical localization of D1 and D2 dopamine receptors in the basal ganglia of the rat: light and electron microscopy. Neuroscience 65:709–730PubMedCrossRefGoogle Scholar
  152. Yung WH, Hausser MA, Jack JJ (1991) Electrophysiology of dopaminergic and non-dopaminergic neurones of the guinea-pig substantia nigra pars compacta in vitro. J Physiol 436:643–667PubMedGoogle Scholar
  153. Zhang D, Yang S, Jin GZ, Bunney BS, Shi WX (2008) Oscillatory firing of dopamine neurons: differences between cells in the substantia nigra and ventral tegmental area. Synapse 62:169–175PubMedCrossRefGoogle Scholar
  154. Zhang L, Liu Y, Chen X (2005) Carbachol induces burst firing of dopamine cells in the ventral tegmental area by promoting calcium entry through L-type channels in the rat. J Physiol 568:469–481PubMedCrossRefGoogle Scholar
  155. Zhou Y, Bunney BS, Shi WX (2006) Differential effects of cocaine on firing rate and pattern of dopamine neurons: role of alpha1 receptors and comparison with L-dopa and apomorphine. J Pharmacol Exp Ther 317:196–201PubMedCrossRefGoogle Scholar
  156. Zolles G, Kloker N, Wenzel D, Weisser-Thomas J, Fleischmann BK, Roeper J, Fakler B (2006) Pacemaking by HCN channels requires interaction with phosphoinositides. Neuron 52:1027–1036PubMedCrossRefGoogle Scholar

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© Springer-Verlag/Wien Printed in Germany 2009

Authors and Affiliations

  1. 1.Department of Pharmaceutical SciencesLoma Linda University School of PharmacyLoma LindaUSA

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