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The Journal of Neuroscience, March 1, 2001, 21(5):1452-1463
Molecular and Physiological Diversity of Nicotinic Acetylcholine
Receptors in the Midbrain Dopaminergic Nuclei
Ruby
Klink1,
Alban
de Kerchove
d'Exaerde1,
Michele
Zoli1, 2, and
Jean-Pierre
Changeux1
1 Laboratoire de Neurobiologie Moléculaire,
Centre National de la Recherche Scientifique Unité de Recherche
Associée 2182 "Récepteurs et Cognition," Institut
Pasteur, 75724 Paris Cédex 15, France, and
2 Department of Biomedical Sciences, Section of Physiology,
University of Modena and Reggio Emilia, 41100 Modena, Italy
Nicotinic acetylcholine receptors (nAChRs) on dopaminergic (DA) and
GABAergic (Gaba) projection neurons of the substantia nigra (SN)
and ventral tegmental area (VTA) are characterized by single-cell
RT-PCR and patch-clamp recordings in slices of rat and wild-type,
2 / , 4 / , and 7 / mice. The eight nAChR subunits
expressed in these nuclei, 3-7 and 2-4, contribute to four
different types of nAChR-mediated currents. Most DA neurons in the SN
and VTA express two nAChR subtypes. One is inhibited by
dihydro- -erythroidine (2 µM), -conotoxin MII (10 nM), and methyllycaconitine (1 nM) but does not
contain the 7 subunit; it possesses a putative
4 6 5( 2)2 composition. The other subtype is
inhibited by dihydro- -erythroidine (2 µM) and has a
putative 4 5( 2)2 composition. Gaba neurons in the
VTA exhibit a third subtype with a putative
( 4)2( 2)3 composition, whereas Gaba
neurons in the SN have either the putative
( 4)2( 2)3 oligomer or the putative
4 6 5( 2)2 oligomer. The fourth subtype, a
putative ( 7)5 homomer, is encountered in less than half
of DA and Gaba neurons, in the SN as well as in the VTA. Neurons in the
DA nuclei thus exhibit a diversity of nAChRs that might differentially
modulate reinforcement and motor behavior.
Key words:
addiction; dopamine; GABA; nAChR; nicotinic; Parkinson's
disease; substantia nigra; ventral tegmental area
Copyright © 2001 Society for Neuroscience 0270-6474/01/2151452-12$05.00/0
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H. N. Nguyen, B. A. Rasmussen, and D. C. Perry
Subtype-Selective Up-Regulation by Chronic Nicotine of High-Affinity Nicotinic Receptors in Rat Brain Demonstrated by Receptor Autoradiography
J. Pharmacol. Exp. Ther.,
December 1, 2003;
307(3):
1090 - 1097.
[Abstract]
[Full Text]
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C. Dowell, B. M. Olivera, J. E. Garrett, S. T. Staheli, M. Watkins, A. Kuryatov, D. Yoshikami, J. M. Lindstrom, and J. M. McIntosh
{alpha}-Conotoxin PIA Is Selective for {alpha}6 Subunit-Containing Nicotinic Acetylcholine Receptors
J. Neurosci.,
September 17, 2003;
23(24):
8445 - 8452.
[Abstract]
[Full Text]
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M. Quik, T. Bordia, M. Okihara, H. Fan, M. J. Marks, J. M. McIntosh, and P. Whiteaker
L-DOPA Treatment Modulates Nicotinic Receptors in Monkey Striatum
Mol. Pharmacol.,
September 1, 2003;
64(3):
619 - 628.
[Abstract]
[Full Text]
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V. P. Grinevich, P. A. Crooks, S. P. Sumithran, A. J. Haubner, J. T. Ayers, and L. P. Dwoskin
N-n-Alkylpyridinium Analogs, a Novel Class of Nicotinic Receptor Antagonists: Selective Inhibition of Nicotine-Evoked [3H]Dopamine Overflow from Superfused Rat Striatal Slices
J. Pharmacol. Exp. Ther.,
September 1, 2003;
306(3):
1011 - 1020.
[Abstract]
[Full Text]
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N. Champtiaux, C. Gotti, M. Cordero-Erausquin, D. J. David, C. Przybylski, C. Lena, F. Clementi, M. Moretti, F. M. Rossi, N. Le Novere, et al.
Subunit Composition of Functional Nicotinic Receptors in Dopaminergic Neurons Investigated with Knock-Out Mice
J. Neurosci.,
August 27, 2003;
23(21):
7820 - 7829.
[Abstract]
[Full Text]
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W. Adriani, S. Spijker, V. Deroche-Gamonet, G. Laviola, M. Le Moal, A. B. Smit, and P. V. Piazza
Evidence for Enhanced Neurobehavioral Vulnerability to Nicotine during Periadolescence in Rats
J. Neurosci.,
June 1, 2003;
23(11):
4712 - 4716.
[Abstract]
[Full Text]
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R. Salas, A. Orr-Urtreger, R. S. Broide, A. Beaudet, R. Paylor, and M. De Biasi
The Nicotinic Acetylcholine Receptor Subunit alpha 5 Mediates Short-Term Effects of Nicotine in Vivo
Mol. Pharmacol.,
May 1, 2003;
63(5):
1059 - 1066.
[Abstract]
[Full Text]
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J. R. A. Wooltorton, V. I. Pidoplichko, R. S. Broide, and J. A. Dani
Differential Desensitization and Distribution of Nicotinic Acetylcholine Receptor Subtypes in Midbrain Dopamine Areas
J. Neurosci.,
April 15, 2003;
23(8):
3176 - 3185.
[Abstract]
[Full Text]
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N. Sahibzada, M. Ferreira Jr, B. Williams, A. Wasserman, S. Vicini, and R. A Gillis
Nicotinic ACh receptor subtypes on gastrointestinally projecting neurones in the dorsal motor vagal nucleus of the rat
J. Physiol.,
December 15, 2002;
545(3):
1007 - 1016.
[Abstract]
[Full Text]
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I. M. Khan, E. Singletary, A. Alemayehu, S. Stanislaus, M. P. Printz, T. L. Yaksh, and P. Taylor
Nicotinic receptor gene cluster on rat chromosome 8 in nociceptive and blood pressure hyperresponsiveness
Physiol Genomics,
October 29, 2002;
11(2):
65 - 72.
[Abstract]
[Full Text]
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M. Zoli, M. Moretti, A. Zanardi, J. M. McIntosh, F. Clementi, and C. Gotti
Identification of the Nicotinic Receptor Subtypes Expressed on Dopaminergic Terminals in the Rat Striatum
J. Neurosci.,
October 15, 2002;
22(20):
8785 - 8789.
[Abstract]
[Full Text]
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X. M. Shao and J. L. Feldman
Pharmacology of Nicotinic Receptors in PreBotzinger Complex That Mediate Modulation of Respiratory Pattern
J Neurophysiol,
October 1, 2002;
88(4):
1851 - 1858.
[Abstract]
[Full Text]
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E. Christophe, A. Roebuck, J. F. Staiger, D. J. Lavery, S. Charpak, and E. Audinat
Two Types of Nicotinic Receptors Mediate an Excitation of Neocortical Layer I Interneurons
J Neurophysiol,
September 1, 2002;
88(3):
1318 - 1327.
[Abstract]
[Full Text]
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A. J. Mogg, P. Whiteaker, J. M. McIntosh, M. Marks, A. C. Collins, and S. Wonnacott
Methyllycaconitine Is a Potent Antagonist of alpha -Conotoxin-MII-Sensitive Presynaptic Nicotinic Acetylcholine Receptors in Rat Striatum
J. Pharmacol. Exp. Ther.,
July 1, 2002;
302(1):
197 - 204.
[Abstract]
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S. R. Grady, K. L. Murphy, J. Cao, M. J. Marks, J. M. McIntosh, and A. C. Collins
Characterization of Nicotinic Agonist-Induced [3H]Dopamine Release from Synaptosomes Prepared from Four Mouse Brain Regions
J. Pharmacol. Exp. Ther.,
May 1, 2002;
301(2):
651 - 660.
[Abstract]
[Full Text]
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M. R. Picciotto and W. A. Corrigall
Neuronal Systems Underlying Behaviors Related to Nicotine Addiction: Neural Circuits and Molecular Genetics
J. Neurosci.,
May 1, 2002;
22(9):
3338 - 3341.
[Abstract]
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P. Whiteaker, C. G. Peterson, W. Xu, J. M. McIntosh, R. Paylor, A. L. Beaudet, A. C. Collins, and M. J. Marks
Involvement of the alpha 3 Subunit in Central Nicotinic Binding Populations
J. Neurosci.,
April 1, 2002;
22(7):
2522 - 2529.
[Abstract]
[Full Text]
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N. Champtiaux, Z.-Y. Han, A. Bessis, F. M. Rossi, M. Zoli, L. Marubio, J. M. McIntosh, and J.-P. Changeux
Distribution and Pharmacology of alpha 6-Containing Nicotinic Acetylcholine Receptors Analyzed with Mutant Mice
J. Neurosci.,
February 15, 2002;
22(4):
1208 - 1217.
[Abstract]
[Full Text]
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H. Neuhoff, A. Neu, B. Liss, and J. Roeper
Ih Channels Contribute to the Different Functional Properties of Identified Dopaminergic Subpopulations in the Midbrain
J. Neurosci.,
February 15, 2002;
22(4):
1290 - 1302.
[Abstract]
[Full Text]
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K. Kawa
Acute synaptic modulation by nicotinic agonists in developing cerebellar Purkinje cells of the rat
J. Physiol.,
January 1, 2002;
538(1):
87 - 102.
[Abstract]
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K. Kawa
Acute synaptic modulation by nicotinic agonists in developing cerebellar Purkinje cells of the rat
J. Physiol.,
January 1, 2002;
538(1):
87 - 102.
[Abstract]
[Full Text]
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