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The Journal of Neuroscience, June 15, 1998, 18(12):4461-4472
Identification of Four Classes of Brain Nicotinic Receptors Using
 2 Mutant Mice
Michele
Zoli1, 2,
Clément
Léna1,
Marina R.
Picciotto1, 3, and
Jean-Pierre
Changeux1
1 Centre National de la Recherche Scientifique
Unité de Recherche Associée D1284, Neurobiologie
Moléculaire, Institut Pasteur, 75724 Paris Cédex 15, France, 2 Section of Physiology, Department of Biomedical
Sciences, University of Modena, Modena, Italy, and
3 Department of Psychiatry, Yale University School of
Medicine, New Haven, Connecticut 06508
Although the expression patterns of the neuronal nicotinic
acetylcholine receptor (nAChR) subunits thus far described are known,
the subunit composition of functional receptors in different brain
areas is an ongoing question. Mice lacking the  2 subunit of the
nAChR were used for receptor autoradiography studies and patch-clamp
recording in thin brain slices. Four distinct types of nAChRs were
identified, expanding on an existing classification [Alkondon M,
Albuquerque EX (1993) Diversity of nicotinic acetylcholine receptors in
rat hippocampal neurons. I. Pharmacological and functional evidence for
distinct structural subtypes. J Pharmacol Exp Ther 265:1455-1473.], and tentatively identifying the subunit composition of nAChRs in different brain regions. Type 1 nAChRs bind
 -bungarotoxin, are not altered in 2  / mice, and contain the
7 subunit. Type 2 nAChRs contain the 2 subunit because they are
absent in 2 / mice, bind all nicotinic agonists used with high
affinity (excluding -bungarotoxin), have an order of potency for
nicotine  cytisine in electrophysiological experiments, and are
likely to be composed of 42 in most brain regions, with other subunits contributing in specific areas. Type 3 nAChRs bind epibatidine with high affinity in equilibrium binding experiments and show that
cytisine is as effective as nicotine in electrophysiological experiments; their distribution and persistence in 2 / mice strongly suggest a subunit composition of 34. Type 4 nAChRs bind
cytisine and epibatidine with high affinity in equilibrium binding
experiments and persist in 2 / mice; cytisine = nicotine in
electrophysiological experiments. Type 4 nAChRs also exhibit faster
desensitization than type 3 nAChRs at high doses of nicotine. Knock-out
animals lacking individual subunits should allow a further
dissection of nAChR subclasses.
Key words:
nicotinic receptor; receptor classification; homologous
recombination; patch clamp; receptor autoradiography; mouse; CNS
Copyright © 1998 Society for Neuroscience 0270-6474/98/18124461-12$05.00/0
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