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
Abstract
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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