Electrophysiological Properties of Midbrain Dopamine Neurons

A. A. Grace
Departments of Neuroscience and Psychiatry
Center for Neuroscience
University of Pittsburgh
Pittsburgh, Pennsylvania 15260.

B. S. Bunney
Department of Psychiatry
Yale University School of Medicine
New Haven, Connecticut 06519


1. Aghajanian GK, Bunney BS. Central dopaminergic neurons: Neurophysiological identification and responses to drugs. In: Snyder SH, Usdin E, eds. Frontiers in catecholamine research. New York: Pergamon Press, 1973;643–648.

2. Alexander GE, DeLong MR, Strick PL. Parallel organization of functionally segregated circuits linking basal ganglia and cortex. Annu Rev Neurosci 1986;9:357–381.

3. Bunney BS, Grace AA. Acute and chronic haloperidol treatment: comparison of effects on nigral dopaminergic cell activity. Life Sci 1978;23:1715–1728.

4. Bunney BS, Walters JR, Roth RH, Aghajanian GK. Dopaminergic neurons: Effect of antipsychotic drugs and amphetamine on single cell activity. J Pharmacol Exp Ther 1973;185:560–571.

5. Charléty PJ, Grenhoff J, Chergui K, de la Chapelle B, Buda M, Svensson TH, Chouvet G. Burst firing of mesencephalic dopamine neurons is inhibited by somatodendritic application of kynurenate. Acta Physiol Scand 1991;142:105–112.

6. Chéramy A, Leviel V, Glowinski J. Dendritic release of dopamine in the substantia nigra. Nature 1981;289:537–542.

7. Cherugi K, Charléty PJ, Akaoka H, Saunier CF, Brunet J-L, Buda M, Svensson TH, Chouvet G. Tonic activation of NMDA receptors causes spontaneous burst discharge of rat midbrain dopamine neurons in vivo. Eur J Neurosci 1993;5:137–144.

8. Chiodo LA, Kapatos G. Mesencephalic neurons in primary culture: Immunohistochemistry and membrane physiology. In: Chiodo LA, Freeman AS, eds. The neurophysiology of dopamine systems. Detroit: Lake Shore Publications, 1987;67–91.

9. Deniau JM, Féger J, LeGuyader C. Striatal evoked inhibition of identified nigrothalamic neurons. Brain Res 1976;104:245–256.

10. Francois C, Percheron G, Yelnick J, Heyner S. Demonstration of the existence of small local circuit neurons in the Golgi-stained primate substantia nigra. Brain Res 1979;172:160–164.

11. Freeman AS, Bunney BS. Activity of A9 and A10 dopaminergic neurons in unrestrained rats: further characterization and effects of apomorphine and cholecystokinin. Brain Res 1987;405:46–55.

12. Freeman AS, Meltzer LT, Bunney BS. Firing properties of substantia nigra dopaminergic neurons in freely moving rats. Life Sci 1985;36:1983–1994.

13. Fujimura K, Matsuda Y. Responses to ramp current stimulation of the neurons in substantia nigra pars compacta in vitro. Brain Res 1988;475:177–181.

14. Fujimura K, Matsuda Y. Autogenous oscillatory potentials in neurons of the guinea pig substantia nigra pars compacta in vitro. Neurosci Lett 1989;104:53–57.

15. Gonon FG. Nonlinear relationship between impulse flow and dopamine released by rat midbrain dopaminergic neurons as studied by in vivo electrochemistry. Neuroscience 1988;24:19–28.

16. Grace AA. The regulation of dopamine neuron activity as determined by in vivo and in vitro intracellular recordings. In: Chiodo LA, Freeman AS, eds. The neurophysiology of dopamine systems. Detroit: Lake Shore Publications, 1987;1–66.

17. Grace AA. Evidence for the functional compartmentalization of spike generating regions of rat midbrain dopamine neurons recorded in vitro. Brain Res 1990;524:31–41.

18. Grace AA. Regulation of spontaneous activity and oscillatory spike firing in rat midbrain dopamine neurons recorded in vitro. Synapse 1991;7:221–234.

19. Grace AA. Phasic versus tonic dopamine release and the modulation of dopamine system responsivity: a hypothesis for the etiology of schizophrenia. Neuroscience 1991;41:1–24.

20. Grace AA. Cortical regulation of subcortical dopamine systems and its possible relevance to schizophrenia. J Neural Transm 1993;91:111–134.

21. Grace AA, Bunney BS. Paradoxical GABA excitation of nigral dopaminergic cells: indirect mediation through reticulata inhibitory interneurons. Eur J Pharmacol 1979;59:211–218.

22. Grace AA, Bunney BS. Nigral dopamine neurons: intracellular recording and identification with L-DOPA injection and histofluorescence. Science 1980;210:654–656.

23. Grace AA, Bunney BS. Intracellular and extracellular electrophysiology of nigral dopaminergic neurons. I. Identification and characterization. Neuroscience 1983;10:301–315.

24. Grace AA, Bunney BS. Intracellular and extracellular electrophysiology of nigral dopaminergic neurons. III. Evidence for electrical coupling. Neuroscience 1983;10:333–348.

25. Grace AA, Bunney BS. The control of firing pattern in nigral dopamine neurons: single spike firing. J. Neurosci 1984;4:2866–2876.

26. Grace AA, Bunney BS. The control of firing pattern in nigral dopamine neurons: burst firing. J Neurosci 1984;4:2877–2890.

27. Grace AA, Bunney BS. Opposing effects of striatonigral feedback pathways on midbrain dopamine cell activity. Brain Res 1985;333:271–284.

28. Grace AA, Bunney BS. Induction of depolarization block in midbrain dopamine neurons by repeated administration of haloperidol: analysis using in vivo intracellular recording. J Pharmacol Exp Ther 1986;238:1092–1100.

29. Grace AA, Onn S-P. Morphology and electrophysiological properties of immunocytochemically identified rat dopamine neurons recorded in vitro. J Neurosci 1989;9:3463–3481.

30. Grenhoff J, Aston-Jones G, Svensson TH. Nicotinic effects on the firing pattern of midbrain dopamine neurons. Acta Physiol Scand 1986;128:351–358.

31. Guyenet PG, Aghajanian GK. Antidromic identification of dopaminergic and other output neurons of the rat substantia nigra. Brain Res 1978;150:69–84.

32. Guyenet PG, Crane JK. Non-dopaminergic nigrostriatal pathway. Brain Res 1981;213:291–305.

33. Hainsworth AH, Roper J, Kappor R, Ashcroft FM. Identification and electrophysiology of isolated pars compacta neurons from guinea-pig substantia nigra. Neuroscience 1991;43:81–93.

34. Hammond C, Deniau JM, Rizk A, Feger J. Electrophysiological demonstration of an excitatory subthalamonigral pathway in the rat. Brain Res 1978;151:235–244.

35. Hollerman JR, Grace AA. The effects of dopamine-depleting brain lesions on the electrophysiological activity of rat substantia nigra dopamine neurons. Brain Res 1990;533:203–212.

36. Hollerman JR, Grace AA. Subthalamic nucleus cell activity in the 6-OHDA-treated rat: basal activity and response to haloperidol. Brain Res 1992;590:291–299.

37. Hollerman JR, Abercrombie ED, Grace AA. Electrophysiological, biochemical, and behavioral studies of acute haloperidol-induced depolarization block of nigral dopamine neurons. Neuroscience 1992;47:589–601.

38. Johnson SW, North RA. Two types of neurone in the rat ventral tegmental area and their synaptic inputs. J Physiol 1992;450:455–468.

39. Johnson SW, Seutin V, North R. Burst firing in dopamine neurons induced by N-methyl-D-aspartate: role of electrogenic sodium pump. Science 1992;258:665–667.

40. Kita T, Chang HT, Kitai ST. Pallidal inputs to subthalamus: intracellular analysis. Brain Res 1983;264:255–265.

41. Kita T, Kita H, Kitai ST. Electrical membrane properties of rat substantia nigra compacta neurons in an in vitro slice preparation. Brain Res 1986;372:21–30.

42. Kondo Y, Iwatsubo K. Diminished responses of nigral dopaminergic neurons to haloperidol and morphine following lesions in the striatum. Brain Res 1980;181:237–240.

43. Lacey MG, Mercuri NB, North RA. Two cell types in rat substantia nigra zona compacta distinguished by membrane properties and the actions of dopamine and opioids. J Neurosci 1989;9:1233–1241.

44. Llinás R, Greenfield SA, Jahnsen H. Electrophysiology of pars compacta cells in the in vitro substantia nigra—a possible mechanism for dendritic release. Brain Res 1984;294:127–132.

45. Mercuri NB, Calabresi P, Bernardi G. Effects of glycine on neurons in the rat substantia nigra zona compacta: in vitro electrophysiological study. Synapse 1990;5:190–200.

46. Mercuri NB, Calabresi P, Bernardi G. Responses of rat substantia nigra compacta neurones to L-DOPA. Br J Pharmacol 1990; 100:257–260.

47. Mereu G, Costa E, Armstrong DM, Vicini S. Glutamate receptor subtypes mediate excitatory synaptic currents of dopamine neurons in midbrain slices. J Neurosci 1991;11:1359–1366.

48. Miller JD, Sanghera MK, German DC. Mesencephalic dopaminergic activity in the behaviorally conditioned rat. Life Sci 1981; 29:1255–1265.

49. Miller WC, DeLong MR. Altered tonic activity of neurons in the globus pallidus and subthalamic nucleus in the primate MPTP model of parkinsonism. In: Carpenter MB, Jayaraman A, eds. The basal ganglia II—structure and function: current concepts. New York: Plenum, 1987;415–427.

50. Mitchell IJ, Clarke CE, Boyce S, Robertson RF, Peggs D, Sambrook MA, Crossman AR. Neural mechanisms underlying parkinsonian symptoms based upon regional uptake of 2-deoxyglucose in monkeys exposed to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. Neuroscience 1989;32:213–226.

51. Nagy JI, Yamamoto T, Shiosaka S, Dewar KM, Whittaker ME, Hertzberg EL. Immunohistochemical localization of gap junction protein in rat CNS: a preliminary account. In: Hertzberg EL, Johnson R, eds. Modern cell biology. Alan R Liss, 1988;375–389.

52. Nakanishi H, Kita H, Kitai ST. 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 1987;437:45–55.

53. Nedergaard S, Flatman JA, Engberg I. Nifedipine- and w-conotoxin-sensitive Ca2+ conductances in guinea-pig substantia nigra pars compacta neurons. J Physiol (Lond) 1993;466:727–747.

54. Ort CA, Futamachi KJ, Peacock JH. Morphology and electrophysiology of ventral mesencephalon nerve cell cultures. Dev Brain Res 1988;39:205–215.

55. Overton P, Clark D. Iontophoretically administered drugs acting at the N-methyl-D-aspartate receptor modulate burst firing in A9 dopamine neurons in the rat. Synapse 1992;10:131–140.

56. Pucak ML, Grace AA. Partial dopamine depletions result in an enhanced sensitivity of residual dopamine neurons to apomorphine. Synapse 1991;9:144–155.

57. Pucak ML, Grace AA. Blockade of somatodendritic autoreceptors on nigral dopamine neurons contributes to the firing rate-increasing effects of dopamine antagonists. Soc Neurosci Abstr 1991;17:1352.

58. Pucak ML, Grace AA. Effects of dopamine antagonist administration on the activity of midbrain dopamine neurons recorded in vitro. Soc Neurosci Abstr 1992;18:277.

59. Rouzaire-Dubois B, Hammond C, Hamon B, Féger J. Pharmacological blockade of the globus pallidus-induced inhibitory response of subthalamic cells in the rat. Brain Res 1980;200:321–329.

60. Schultz W. Activity of dopamine neurons in the behaving primate. Semin Neurosci 1992;4:129–138.

61. Schultz W, Apicella P, Ljungberg T. Responses of monkey dopamine neurons to reward and conditioned stimuli during successive steps of learning a delayed response task. J Neurosci 1993;13:900–913.

62. Seutin V, Verbanck P, Massotee L, Dresse A. Evidence for the presence of N-methyl-D-aspartate receptors in the ventral tegmental area of the rat: an electrophysiological in vitro study. Brain Res 1990;514:147–150.

63. Shepard PD, Bunney BS. Effects of apamin on the discharge properties of putative dopamine-containing neurons in vitro. Brain Res 1988;463:380–384.

64. Silva NL, Pechuar CM, Barker JL. Postnatal rat nigrostriatal dopaminergic neurons exhibit five types of potassium conductances. J Neurophysiol 1990;64:262–272.

65. Smith ID, Grace AA. The regulation of nigral dopamine neuron firing by afferents from the subthalamic nucleus. Synapse 1992;12:287–303.

66. Svensson TH, Tung C-S. Local cooling of pre-frontal cortex induces pacemaker-like firing of dopamine neurons in rat ventral tegmental area in vivo. Acta Physiol Scand 1989;136:135–136.

67. Tepper JM, Sawyer SF, Groves PM. Electrophysiologically identified nigral dopaminergic neurons intracellularly labeled with HRP: light-microscopic analysis. J Neurosci 1987;7:2794–2806.

68. Wuerthele SM, Freed WJ, Olson L, Morihisa J, Spoor L, Wyatt RJ, Hoffer BJ. Effect of dopamine agonists and antagonists on the electrical activity of substantia nigra neurons transplanted into the lateral ventricle of the rat. Exp Brain Res 1981;44:1–10.

69. Yung WH, Hausser MA, Jack JB. Electrophysiology of dopaminergic and non-dopaminergic neurones of the guinea-pig substantia nigra pars compacta in vitro. J Physiol (Lond) 1991;436:643–667.

70. Zigmond MJ, Berger TW, Grace AA, Stricker EM. Compensatory responses to nigrostriatal bundle injury: studies with 6-hydroxydopamine in an animal model of parkinsonism. Mol Chem Neuropathol 1989;10:185–200.

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published 2000