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Towards an Understanding of Integrative Brain Functions

Brain nicotinic receptors: structure and regulation, role in learning and reinforcement

Jean-Pierre Changeux*, Daniel Bertrand1, Pierre-Jean Corringer, Stanislas Dehaene2, Stuart Edelstein3, Clément Léna, Nicolas Le Novère, Lisa Marubio, Marina Picciotto4, Michele Zoli5

Neurobiologie Moléculaire, CNRS URA 1284, Institut Pasteur, 25-28 rue du Dr. Roux, 75724, Paris Cedex 15, France

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 neuronal 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 eleboration 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).

*Corresponding author.
1) Present address: CHU, Dept. of Physiology, 2, rue Michael Servet, CH 1211 Geneve 4, Switzerland.
2) Present address: INSERM U334, SHFJ CEA, 4 Place du Gl. Leclerc, 91401 Orsay Cedex, France.
3) Present address: Dept. de Biochimie, Université de Genève, Quai Ernest-Ansermet 30, CH-1211 Geneve 4, Switzerland.
4) Present address: Dept of Psychiatry, Yale University Medical School, Connecticut Mental Health Center, 34 Park Street, New Haven, Connecticut 06508, USA.
5) Present address: Dipartimiento di Scienze Biomediche, Sezione di Fisiologia, Universita di Modena, Via Campi 287, I-41100 Modena, Italy.

Brain Research Reviews 26 (1998) 198-216
Copyright © 1998 Elsevier Science B. V. All rights reserved.


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