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. 1992 May;450:455–468. doi: 10.1113/jphysiol.1992.sp019136

Two types of neurone in the rat ventral tegmental area and their synaptic inputs.

S W Johnson 1, R A North 1
PMCID: PMC1176131  PMID: 1331427

Abstract

1. Intracellular recordings were made from 241 ventral tegmental neurones in slices of rat midbrain. Seventy-seven per cent of neurones were hyperpolarized by dopamine (principal cells); 16% were hyperpolarized by opioid peptides (secondary cells). 2. Most principal cells fired spontaneously (1-3 Hz) with a threshold of -53 mV; most secondary cells did not fire spontaneously. Action potentials of principal cells were longer (0.9 ms) than those of secondary cells (0.5 ms). 3. Focal electrical stimulation within the ventral tegmental area evoked a biphasic synaptic potential, depolarization followed by hyperpolarization, with a duration of about 200 ms. Experiments with receptor antagonists showed that the depolarizing component resulted from activation of both N-methyl-D-aspartate (NMDA) and non-NMDA receptors and the hyperpolarizing component resulted from activation of GABAA receptors. 4. A later hyperpolarizing synaptic potential developed after a latency of 50 ms, reached its peak in 250 ms and had a duration of about 1 s. It reversed polarity at -108 mV (external potassium concentration was 2.5 mM), was blocked by phaclofen (30 microM-1 mM) or 2-hydroxysaclofen (100-300 microM). In some cells, a phaclofen-resistant component remained that was increased by cocaine and blocked by sulpiride (1 microM). 5. It is concluded that the ventral tegmental area contains two types of neurone having properties similar to those in the substantia nigra. The cells receive synaptic inputs mediated by excitatory amino acids acting at NMDA and non-NMDA receptors, GABA acting at GABAA and GABAB receptors, and dopamine acting at D2 receptors.

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Selected References

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  1. Bayer V. E., Pickel V. M. Ultrastructural localization of tyrosine hydroxylase in the rat ventral tegmental area: relationship between immunolabeling density and neuronal associations. J Neurosci. 1990 Sep;10(9):2996–3013. doi: 10.1523/JNEUROSCI.10-09-02996.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Beckstead R. M., Domesick V. B., Nauta W. J. Efferent connections of the substantia nigra and ventral tegmental area in the rat. Brain Res. 1979 Oct 19;175(2):191–217. doi: 10.1016/0006-8993(79)91001-1. [DOI] [PubMed] [Google Scholar]
  3. Bozarth M. A., Wise R. A. Intracranial self-administration of morphine into the ventral tegmental area in rats. Life Sci. 1981 Feb 2;28(5):551–555. doi: 10.1016/0024-3205(81)90148-x. [DOI] [PubMed] [Google Scholar]
  4. Cherubini E., North R. A., Williams J. T. Synaptic potentials in rat locus coeruleus neurones. J Physiol. 1988 Dec;406:431–442. doi: 10.1113/jphysiol.1988.sp017389. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Christie M. J., Bridge S., James L. B., Beart P. M. Excitotoxin lesions suggest an aspartatergic projection from rat medial prefrontal cortex to ventral tegmental area. Brain Res. 1985 Apr 29;333(1):169–172. doi: 10.1016/0006-8993(85)90140-4. [DOI] [PubMed] [Google Scholar]
  6. Corbett D., Wise R. A. Intracranial self-stimulation in relation to the ascending dopaminergic systems of the midbrain: a moveable electrode mapping study. Brain Res. 1980 Mar 3;185(1):1–15. doi: 10.1016/0006-8993(80)90666-6. [DOI] [PubMed] [Google Scholar]
  7. Dilts R. P., Kalivas P. W. Autoradiographic localization of mu-opioid and neurotensin receptors within the mesolimbic dopamine system. Brain Res. 1989 May 29;488(1-2):311–327. doi: 10.1016/0006-8993(89)90723-3. [DOI] [PubMed] [Google Scholar]
  8. Dutar P., Nicoll R. A. A physiological role for GABAB receptors in the central nervous system. Nature. 1988 Mar 10;332(6160):156–158. doi: 10.1038/332156a0. [DOI] [PubMed] [Google Scholar]
  9. Egan T. M., Henderson G., North R. A., Williams J. T. Noradrenaline-mediated synaptic inhibition in rat locus coeruleus neurones. J Physiol. 1983 Dec;345:477–488. doi: 10.1113/jphysiol.1983.sp014990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Fibiger H. C., LePiane F. G., Jakubovic A., Phillips A. G. The role of dopamine in intracranial self-stimulation of the ventral tegmental area. J Neurosci. 1987 Dec;7(12):3888–3896. doi: 10.1523/JNEUROSCI.07-12-03888.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Finley J. C., Maderdrut J. L., Petrusz P. The immunocytochemical localization of enkephalin in the central nervous system of the rat. J Comp Neurol. 1981 Jun 1;198(4):541–565. doi: 10.1002/cne.901980402. [DOI] [PubMed] [Google Scholar]
  12. Grace A. A., Bunney B. S. Nigral dopamine neurons: intracellular recording and identification with L-dopa injection and histofluorescence. Science. 1980 Nov 7;210(4470):654–656. doi: 10.1126/science.7433992. [DOI] [PubMed] [Google Scholar]
  13. Grace A. A. In vivo and in vitro intracellular recordings from rat midbrain dopamine neurons. Ann N Y Acad Sci. 1988;537:51–76. doi: 10.1111/j.1749-6632.1988.tb42096.x. [DOI] [PubMed] [Google Scholar]
  14. Grace A. A., Onn S. P. Morphology and electrophysiological properties of immunocytochemically identified rat dopamine neurons recorded in vitro. J Neurosci. 1989 Oct;9(10):3463–3481. doi: 10.1523/JNEUROSCI.09-10-03463.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Haber S. N., Groenewegen H. J., Grove E. A., Nauta W. J. Efferent connections of the ventral pallidum: evidence of a dual striato pallidofugal pathway. J Comp Neurol. 1985 May 15;235(3):322–335. doi: 10.1002/cne.902350304. [DOI] [PubMed] [Google Scholar]
  16. Hattori T., McGeer P. L., Fibiger H. C., McGeer E. G. On the source of GABA-containing terminals in the substantia nigra. Electron microscopic autoradiographic and biochemical studies. Brain Res. 1973 May 17;54:103–114. doi: 10.1016/0006-8993(73)90037-1. [DOI] [PubMed] [Google Scholar]
  17. Holmes L. J., Wise R. A. Contralateral circling induced by tegmental morphine: anatomical localization, pharmacological specificity, and phenomenology. Brain Res. 1985 Feb 4;326(1):19–26. doi: 10.1016/0006-8993(85)91380-0. [DOI] [PubMed] [Google Scholar]
  18. Koob G. F., Swerdlow N. R. The functional output of the mesolimbic dopamine system. Ann N Y Acad Sci. 1988;537:216–227. doi: 10.1111/j.1749-6632.1988.tb42108.x. [DOI] [PubMed] [Google Scholar]
  19. Lacey M. G., Mercuri N. B., North R. A. Dopamine acts on D2 receptors to increase potassium conductance in neurones of the rat substantia nigra zona compacta. J Physiol. 1987 Nov;392:397–416. doi: 10.1113/jphysiol.1987.sp016787. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Lacey M. G., Mercuri N. B., North R. A. On the potassium conductance increase activated by GABAB and dopamine D2 receptors in rat substantia nigra neurones. J Physiol. 1988 Jul;401:437–453. doi: 10.1113/jphysiol.1988.sp017171. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Lacey M. G., Mercuri N. B., North R. A. Two cell types in rat substantia nigra zona compacta distinguished by membrane properties and the actions of dopamine and opioids. J Neurosci. 1989 Apr;9(4):1233–1241. doi: 10.1523/JNEUROSCI.09-04-01233.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Lyness W. H., Friedle N. M., Moore K. E. Destruction of dopaminergic nerve terminals in nucleus accumbens: effect on d-amphetamine self-administration. Pharmacol Biochem Behav. 1979 Nov;11(5):553–556. doi: 10.1016/0091-3057(79)90040-6. [DOI] [PubMed] [Google Scholar]
  23. Madison D. V., Nicoll R. A. Enkephalin hyperpolarizes interneurones in the rat hippocampus. J Physiol. 1988 Apr;398:123–130. doi: 10.1113/jphysiol.1988.sp017033. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Mereu G., Costa E., Armstrong D. M., Vicini S. Glutamate receptor subtypes mediate excitatory synaptic currents of dopamine neurons in midbrain slices. J Neurosci. 1991 May;11(5):1359–1366. doi: 10.1523/JNEUROSCI.11-05-01359.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Mogenson G. J., Wu M., Manchanda S. K. Locomotor activity initiated by microinfusions of picrotoxin into the ventral tegmental area. Brain Res. 1979 Feb 2;161(2):311–319. doi: 10.1016/0006-8993(79)90072-6. [DOI] [PubMed] [Google Scholar]
  26. Nemeroff C. B., Bissette G. Neuropeptides, dopamine, and schizophrenia. Ann N Y Acad Sci. 1988;537:273–291. doi: 10.1111/j.1749-6632.1988.tb42113.x. [DOI] [PubMed] [Google Scholar]
  27. Newberry N. R., Nicoll R. A. A bicuculline-resistant inhibitory post-synaptic potential in rat hippocampal pyramidal cells in vitro. J Physiol. 1984 Mar;348:239–254. doi: 10.1113/jphysiol.1984.sp015107. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. North R. A. Twelfth Gaddum memorial lecture. Drug receptors and the inhibition of nerve cells. Br J Pharmacol. 1989 Sep;98(1):13–28. doi: 10.1111/j.1476-5381.1989.tb16855.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Pan Z. Z., Colmers W. F., Williams J. T. 5-HT-mediated synaptic potentials in the dorsal raphe nucleus: interactions with excitatory amino acid and GABA neurotransmission. J Neurophysiol. 1989 Aug;62(2):481–486. doi: 10.1152/jn.1989.62.2.481. [DOI] [PubMed] [Google Scholar]
  30. Pan Z. Z., Williams J. T. GABA- and glutamate-mediated synaptic potentials in rat dorsal raphe neurons in vitro. J Neurophysiol. 1989 Apr;61(4):719–726. doi: 10.1152/jn.1989.61.4.719. [DOI] [PubMed] [Google Scholar]
  31. Pan Z. Z., Williams J. T., Osborne P. B. Opioid actions on single nucleus raphe magnus neurons from rat and guinea-pig in vitro. J Physiol. 1990 Aug;427:519–532. doi: 10.1113/jphysiol.1990.sp018185. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Phillips A. G., Fibiger H. C. The role of dopamine in maintaining intracranial self-stimulation in the ventral tegmentum, nucleus accumbens, and medial prefrontal cortex. Can J Psychol. 1978 Jun;32(2):58–66. doi: 10.1037/h0081676. [DOI] [PubMed] [Google Scholar]
  33. Roberts D. C., Corcoran M. E., Fibiger H. C. On the role of ascending catecholaminergic systems in intravenous self-administration of cocaine. Pharmacol Biochem Behav. 1977 Jun;6(6):615–620. doi: 10.1016/0091-3057(77)90084-3. [DOI] [PubMed] [Google Scholar]
  34. Schwartzkroin P. A., Mathers L. H. Physiological and morphological identification of a nonpyramidal hippocampal cell type. Brain Res. 1978 Nov 17;157(1):1–10. doi: 10.1016/0006-8993(78)90991-5. [DOI] [PubMed] [Google Scholar]
  35. Smith G. P., Schneider L. H. Relationships between mesolimbic dopamine function and eating behavior. Ann N Y Acad Sci. 1988;537:254–261. doi: 10.1111/j.1749-6632.1988.tb42111.x. [DOI] [PubMed] [Google Scholar]
  36. Svensson T. H., 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 May;136(1):135–136. doi: 10.1111/j.1748-1716.1989.tb08640.x. [DOI] [PubMed] [Google Scholar]
  37. Thalmann R. H. Evidence that guanosine triphosphate (GTP)-binding proteins control a synaptic response in brain: effect of pertussis toxin and GTP gamma S on the late inhibitory postsynaptic potential of hippocampal CA3 neurons. J Neurosci. 1988 Dec;8(12):4589–4602. doi: 10.1523/JNEUROSCI.08-12-04589.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Waddington J. L., Cross A. J. Neurochemical changes following kainic acid lesions of the nucleus accumbens: implications for a GABAergic accumbal-ventral tegmental pathway. Life Sci. 1978 Mar;22(11):1011–1014. doi: 10.1016/0024-3205(78)90367-3. [DOI] [PubMed] [Google Scholar]
  39. Williams J. T., North R. A., Shefner S. A., Nishi S., Egan T. M. Membrane properties of rat locus coeruleus neurones. Neuroscience. 1984 Sep;13(1):137–156. doi: 10.1016/0306-4522(84)90265-3. [DOI] [PubMed] [Google Scholar]
  40. Yim C. Y., Mogenson G. J. Electrophysiological studies of neurons in the ventral tegmental area of Tsai. Brain Res. 1980 Jan 13;181(2):301–313. doi: 10.1016/0006-8993(80)90614-9. [DOI] [PubMed] [Google Scholar]
  41. Yoshimura M., Higashi H. 5-Hydroxytryptamine mediates inhibitory postsynaptic potentials in rat dorsal raphe neurons. Neurosci Lett. 1985 Jan 7;53(1):69–74. doi: 10.1016/0304-3940(85)90099-0. [DOI] [PubMed] [Google Scholar]
  42. Yung W. H., Häusser M. A., Jack J. J. Electrophysiology of dopaminergic and non-dopaminergic neurones of the guinea-pig substantia nigra pars compacta in vitro. J Physiol. 1991 May;436:643–667. doi: 10.1113/jphysiol.1991.sp018571. [DOI] [PMC free article] [PubMed] [Google Scholar]

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