Brain nicotinic receptors: structure and regulation, role in learning and reinforcement
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The introduction, in the late sixties, of the concepts and methods of molecular biology to the study of the nervous system had a profound impact on the field, primarily through the identification of its basic molecular components. These structures include, for example, the elementary units of the synapse: neurotransmitters, neuropeptides and their receptors, but also ionic channels, intracellular second messengers and the relevant enzymes, cell surface adhesion molecules, or growth and trophic factors [21,78,81, 52,79]. Attempts to establish appropriate causal relationships between these molecular components, the actual organisation of neural networks, and a defined behavior, nevertheless, still must overcome many difficulties. A first problem is the recognition of the minimum levels of organisation, from the molecular, cellular, or multicellular (circuit) to the higher cognitive levels, that determine the given physiological and/or behavioral performance under investigation. A common difficulty (and potential source of errors of interpretation) is to relate a cognitive function to a network organization which does not possess the required structural complexity and vice-versa. Another problem is to distinguish, among the components of the system, those which are actually necessary and those which, taken together, suffice for a given behavior to take place. Identification of such a minimal set of building blocks may receive decisive insights from the elaboration of neurally plausible formal models that bring together, within a single and coherent 'artificial organism', the neuronal network, the circulating activity, and the behavior they determine (see [42,43,45,72,30]). In this communication, we shall attempt, still in a preliminary fashion, to bring together: (1) our recent knowledge on the molecular biology of brain nicotinic receptors (nAChRs) and their allosteric properties and (2) integrated behaviors, such as cognitive learning, investigated for instance with delayed-response or passive avoidance tasks that are likely to involve nAChRs in particular at the level of reinforcement (or reward) mechanisms (see [18,29,135]).
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Nicotinic receptors function as non-selective, excitatory cation channels.
“Nicotinic receptors function as non-selective, excitatory cation channels (Changeux et al., 1998; Picciotto et al., 2001) and occur as homomeric or heteromeric assemblies of a large family of α- and β-subunits (α2-α7 and β2-β4; reviewed in (Picciotto et al., 2000)).”
From Acetylcholine as a Neuromodulator: Cholinergic Signaling Shapes Nervous System Function and Behavior (2012) · cites this paper as Changeux et al., 1998
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Self-citationBoyd, N. D., & Cohen, J. B. (1980) · Biochemistry · doi:10.1021/bi00564a031 · Cited by 139 · see citing works
Molecular Structure of the Nicotinic Acetylcholine ReceptorPreprint
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Conformations of Torpedo acetylcholine receptor associated with ion transport and desensitization
Neubig, R. R., Boyd, N. D., & Cohen, J. B. (1982) · Biochemistry · doi:10.1021/bi00257a032 · Cited by 136 · see citing works
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A kinetic mechanism for nicotinic acetylcholine receptors based on multiple allosteric transitions.
Edelstein, S. J., Schaad, O., Henry, E., Bertrand, D., & Changeux, J.-P. (1996) · Biological Cybernetics · doi:10.1007/s004220050302 · Cited by 134 · see citing works
Self-citationReceptor-receptor interactions as an integrative mechanism in nerve cells
Zoli, M., Agnati, L. F., Hedlund, P. B., Li, X., Ferré, S., & Fuxé, K. (1993) · Molecular Neurobiology · doi:10.1007/bf02769180 · Cited by 129 · see citing works
Self-citationA Simple Model of Prefrontal Cortex Function in Delayed-Response Tasks
Dehaene, S., & Changeux, J. (1989) · Journal of Cognitive Neuroscience · doi:10.1162/jocn.1989.1.3.244 · Cited by 126 · see citing works
Self-citationNakazawa, K. (1994) · Journal of Neuroscience · doi:10.1523/jneurosci.14-02-00740.1994 · Cited by 123 · see citing works
A molecular view of neurotransmitter receptors and ionic channels.
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Mathie, A. A., Colquhoun, D. M., & Cull-Candy, S. G. (1990) · The Journal of Physiology · doi:10.1113/jphysiol.1990.sp018191 · Cited by 119 · see citing works
Mulle, C., & Changeux, J. (1990) · Journal of Neuroscience · doi:10.1523/jneurosci.10-01-00169.1990 · Cited by 107 · see citing works
Self-citationCorringer, P., Bertrand, S., Bohler, S., Edelstein, S. J., Changeux, J., & Bertrand, D. (1998) · Journal of Neuroscience · doi:10.1523/jneurosci.18-02-00648.1998 · Cited by 106 · see citing works
Self-citationGalzi, J. L., Revah, F., Bouet, F., et al. (1991) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.88.11.5051 · Cited by 103 · see citing works
Heidmann, T., & Changeux, J. (1979) · European Journal of Biochemistry · doi:10.1111/j.1432-1033.1979.tb12894.x · Cited by 103 · see citing works
Self-citationThe multiple phenotypes of allosteric receptor mutants.
Galzi, J. L., Edelstein, S. J., & Changeux, J. (1996) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.93.5.1853 · Cited by 99 · see citing works
Self-citationIwata, S., Kamata, K., Yoshida, S., Minowa, T., & Ohta, T. (1994) · Nature Structural Biology · doi:10.1038/nsb0394-176 · Cited by 96 · see citing works
Heidmann, T., & Changeux, J. (1980) · Biochemical and Biophysical Research Communications · doi:10.1016/0006-291x(80)91460-6 · Cited by 95 · see citing works
Self-citationNicotinic receptor: an allosteric protein specialized for intercellular communication
Bertrand, D., & Changeux, J. (1995) · Seminars in Neuroscience · doi:10.1006/smns.1995.0010 · Cited by 94 · see citing works
Self-citationBarium permeability of neuronal nicotinic receptor alpha 7 expressed in Xenopus oocytes
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The macro- and microarchitectures of the ligand-binding domain of glutamate receptors
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Amador, M., & Dani, J. (1995) · Journal of Neuroscience · doi:10.1523/jneurosci.15-06-04525.1995 · Cited by 81 · see citing works
Stratification of the channel domain in neurotransmitter receptors
Bertrand, D., Galzi, J., Devillers‐Thiéry, A., Bertrand, S., & Changeux, J. (1993) · Current Opinion in Cell Biology · doi:10.1016/0955-0674(93)90141-c · Cited by 81 · see citing works
Self-citationClarke, P. B. S. (1993) · Progress in brain research · doi:10.1016/s0079-6123(08)62383-3 · Cited by 80 · see citing works
Oswald, R. E., & Changeux, J. (1982) · FEBS Letters · doi:10.1016/0014-5793(82)80857-0 · Cited by 79 · see citing works
Self-citationGoodman, F. R. (1974) · Neuropharmacology · doi:10.1016/0028-3908(74)90093-8 · Cited by 78 · see citing works
Vidal, C., & Changeux, J. (1989) · Neuroscience · doi:10.1016/0306-4522(89)90056-0 · Cited by 76 · see citing works
Self-citationSteroids inhibit nicotinic acetylcholine receptors
Bertrand, D., Valera, S., Bertrand, S., Ballivet, M., & Rungger, D. (1991) · Neuroreport · doi:10.1097/00001756-199105000-00016 · Cited by 75 · see citing works
Self-citationParadoxical allosteric effects of competitive inhibitors on neuronal α7 nicotinic receptor mutants
Bertrand, S., Devillers‐Thiéry, A., Palma, E., Buisson, B., Edelstein, S. J., Corringer, P., Changeux, J., & Bertrand, D. (1997) · Neuroreport · doi:10.1097/00001756-199711100-00034 · Cited by 70 · see citing works
Self-citationAlbuquerque, E. X., Pereira, E. F. R., Alkondon, M., Schrattenholz, A. S., & Maelicke, A. (1997) · Journal of Receptors and Signal Transduction · doi:10.3109/10799899709036607 · Cited by 66 · see citing works
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Self-citationAllosteric Transitions of the Acetylcholine Receptor
Edelstein, S. J., & Changeux, J. (1998) · Advances in protein chemistry · doi:10.1016/s0065-3233(08)60652-x · Cited by 61 · see citing works
Self-citationA model for reading morphogenetic gradients: autocatalysis and competition at the gene level.
Kerszberg, M., & Changeux, J. (1994) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.91.13.5823 · Cited by 60 · see citing works
Self-citationStratified organization of the nicotinic acetylcholine receptor channel
Devillers‐Thiéry, A., Galzi, J., Bertrand, S., Changeux, J., & Bertrand, D. (1992) · Neuroreport · doi:10.1097/00001756-199211000-00014 · Cited by 55 · see citing works
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McMahon, L. L., Yoon, K.-W., & Chiappinelli, V. A. (1994) · Journal of Neurophysiology · doi:10.1152/jn.1994.71.2.826 · Cited by 50 · see citing works
Heterogeneity of neuronal nicotinic acetylcholine receptors in thin slices of rat medial habenula.
Connolly, J. G., Gibb, A. J., & Colquhoun, D. M. (1995) · The Journal of Physiology · doi:10.1113/jphysiol.1995.sp020650 · Cited by 48 · see citing works
A Novel Agonist Binding Site on Nicotinic Acetylcholine Receptors
Pereira, E. F. R., Alkondon, M., Tano, T., et al. (1993) · Journal of Receptor Research · doi:10.3109/10799899309073670 · Cited by 44 · see citing works
Forster, I. C., & Bertrand, D. (1995) · Proceedings of the Royal Society B Biological Sciences · doi:10.1098/rspb.1995.0071 · Cited by 42 · see citing works
Self-citationInward rectification of acetylcholine‐elicited currents in rat phaeochromocytoma cells.
Ifune, C. K., & Steinbach, J. H. (1992) · The Journal of Physiology · doi:10.1113/jphysiol.1992.sp019369 · Cited by 41 · see citing works
Picciotto, M. R., Zoli, M., Zachariou, V., & Changeux, J. (1997) · Biochemical Society Transactions · doi:10.1042/bst0250824 · Cited by 35 · see citing works
Self-citationEdelstein, S. J., & Changeux, J. (1996) · Cellular and Molecular Life Sciences · doi:10.1007/bf01952106 · Cited by 33 · see citing works
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An allosteric mechanism for the acetylcholine receptor
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Self-citationUN MODELE MOLECULAIRE DE REGULATION D'EFFICACITE AU NIVEAU POSTSYNAPTIQUE D'UNE SYNAPSE CHIMIQUE
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Self-citationMyasthenic nicotinic receptor mutant interpreted in terms of the allosteric model
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Self-citationFunction and dysfunction in the nervous system
Harmar, A. J., & Ogilvie, A. D. (1996) · Trends in Neurosciences · doi:10.1016/s0166-2236(96)30014-3 · Cited by 11 · see citing works
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Acetylcholine as a Neuromodulator: Cholinergic Signaling Shapes Nervous System Function and Behavior
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Chronic Exposure to Nicotine Upregulates the Human α4β2 Nicotinic Acetylcholine Receptor Function
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Self-citationSelective Excitation of Subtypes of Neocortical Interneurons by Nicotinic Receptors
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Nicotine addiction: the possible role of functional upregulation
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Effect of nicotine on cerebellar granule neuron development
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Neurostimulation techniques in the treatment of nicotine dependence: a review
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- Authors
- Changeux, J.-P., Bertrand, D., Corringer, P.-J., Dehaene, S., Edelstein, S., Léna, C., Le Novère, N., Marubio, L., Picciotto, M., & Zoli, M.
- Affiliations
- Centre National de la Recherche Scientifique (FR)
- Corresponding author
- Changeux, Jean-Pierre
- ORCID
- Venue
- Brain Research Reviews
- Publisher
- Elsevier BV
- Published
- 1998-05
- Volume
- 26
- Issue
- 2-3
- Pages
- 198-216
- ISSN
- 0165-0173 (ISSN-L)
- OpenAlex
- W1544301323
- Cited by
- 322
- References
- 155
- Citations by year
- 2026: 2 · 2025: 4 · 2024: 10 · 2023: 8 · 2022: 2 · 2021: 5 · 2020: 28 · 2019: 4 · 2018: 6 · 2017: 5 · 2016: 5 · 2015: 9 · 2014: 10 · 2013: 6 · 2012: 8
- FWCI
- 1.84
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Brain Research Reviews (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- IRIS UNIMORE (University of Modena and Reggio Emilia) (submittedVersion, cc-by-nc-nd)
- Funders
- Centre National de la Recherche Scientifique
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nicotinic Acetylcholine Receptors Study
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Health Sciences › Medicine › Physiology › Smoking Behavior and Cessation
- Keywords
- nicotinic acetylcholine receptors, allosteric regulation, receptor structure, learning, reinforcement, reward processing, delayed response, passive avoidance, neural network organization
- MeSH terms
- Allosteric Regulation, Animals, Binding Sites, Brain, Cognition, Humans, Learning, Models, Neurological, Nerve Net, Neurons, Receptors, Nicotinic, Reinforcement, Psychology, Mutagenesis, Site-Directed, Evolution, Molecular
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