Jean-Pierre Changeux

Jean-Pierre Changeux (French: [ʃɑ̃ʒø]; born 6 April

1936) is a French neuroscientist known for his research Jean-Pierre Changeux
in several fields of biology, from the structure and
function of proteins (with a focus on the allosteric
proteins), to the early development of the nervous
system up to cognitive functions. Although being
famous in biological sciences for the MWC model, the
identification and purification of the nicotinic
acetylcholine receptor and the theory of epigenesis by
synapse selection are also notable scientific
achievements. Changeux is known by the non-
scientific public for his ideas regarding the connection
between mind and physical brain. As put forth in his
book, Conversations on Mind, Matter and
Mathematics, Changeux strongly supports the view Born 6 April 1936
that the nervous system functions in a projective rather Domont, France
than reactive style and that interaction with the Education École Normale Supérieure
environment, rather than being instructive, results in Pasteur Institute
the selection amongst a diversity of preexisting internal Known for MWC model, isolation of
representations. nAChR
Spouse Annie Dupont (m. 1962)
Children 1 son
Biography
Awards Wolf Prize in Medicine (1982)
Changeux was born in Domont, France to Marcel Louis-Jeantet Prize for
Changeux and Jeanne Benoît.[2] He entered the École Medicine (1993)[1]
Normale Supérieure in 1955, where he obtained a Sir Hans Krebs Medal (1994)
bachelor's degree (Licence) in 1957 and a master's Balzan Prize (2001)
degree (Diplome d'Études Supérieure) in 1958. He also Albert Einstein World Award of
received his agrégation in natural science the same Science (2018)
year. He began his scientific career during his ENS Scientific career
years during summer internships in Banyuls-sur-Mer Fields Neuroscience
where he identified a new genus of parasitic Copepod.
Institutions Collège de France
He pursued PhD studies at the Pasteur Institute under
Institut Pasteur
the direction of Jacques Monod and François Jacob,
and gained his doctorate in 1964. Changeux then left Doctoral Jacques Monod, François
France for postdoctoral studies first at the University advisors Jacob
of California Berkeley (1965–1966) then at Columbia
University College of Physicians and Surgeons, New York (1967). He returned to France as attaché to the
chair of Molecular Biology held by Jacques Monod. In 1972, he became director of the Unit of Molecular
Neurobiology at the Pasteur Institute, where he received a professorship in 1975. In 1975, Changeux was
elected professor at the Collège de France, chair of Cell Communications, position that he held until
2006. Changeux is author of more than 600 scientific articles and several books, technical or for general
audience.

Scientific achievements
All his scientific career, Changeux has been faithful to a handful of scientific questions, at molecular,
cellular and brain levels. If one needs to seek a unifying theme to all of them, it is the conviction that
selection is the basis of life processes, rather than instruction. While started as separate lines of
investigations, all the research threads were tied in the recent decades within the study of allosteric
mechanisms as a basis of for the involvement of nicotinic receptors in cognitive functions.

Allostery
During his PhD studies in the laboratory of Jacques Monod and
François Jacob, Changeux studied the allosteric regulations of
enzymes, that is the modulation of their activity by compounds
different from their substrates.[3][4][5] This work led to the
development of the model of concerted transitions for allosteric
proteins.[6][7] The main ideas behind this theory are: 1) proteins
Diagram representing an allosteric
can exist under various conformations in thermal equilibrium in transition of a protein between R
the absence of regulators. The allosteric regulators merely shift the and T states, stabilised by an
equilibrium between the conformations, stabilizing the ones for Agonist, and Inhibitor and a
which they display the highest affinity, and 2) all the subunits of a Substrate. Adapted from Changeux
symmetrical multimeric protein exist in the same conformation, and Edelstein (2004) Nicotinic
the transition taking place in a concerted fashion. The resulting Acetylcholine Receptors: From
Molecular Biology to Cognition.
model explains the observed cooperativity without a progressive
change of biophysical parameters. This conceptual framework is
still the principal model used to explain the function of cooperative proteins such as hemoglobin.

In his PhD thesis, Changeux suggested that the recognition and transmission of signals by membrane, and
in particular by synapses, could use the same mechanisms as the allosteric regulation of enzymes. More
than forty years of research would follow, mainly focussed on nicotinic acetylcholine receptors (see
below). In 1967, Changeux extended the MWC model to bi-dimensional lattice of receptors[8] (an idea
that would also be developed three decades afterward by Dennis Bray[9]). He then applied this idea to the
post-synaptic membrane of electric organs (analog to striated muscle).[10][11] His team demonstrated the
existence of several interconvertible states for the nicotinic receptor, resting, open and desensitized,
displaying different affinities for the ligands, such as the endogenous agonist acetylcholine.[12][13][14] The
transitions between the states followed different kinetics, and those kinetics plus the differential affinities
sufficed to explain the shape of the post-synaptic potential. A full mechanistic model of the nicotinic
receptor from striated muscle (or electric organ) was to be provided much later, when Changeux
collaborated with Stuart Edelstein, another specialist of allostery, who worked decades on
hemoglobin.[15] In addition to the allosteric modulation of the channel gating by the agonists, many other
regulations of the ligand-gated ion channels activity have since been discovered. The modulators bind to
a variety of allosteric sites, whether on the agonist binding sites, other binding sites at the subunit
interfaces, on the cytoplasmic part of the protein or in the transmembrane domain.[16]
The concept of an allosteric pharmacology[17] for ion channels was developed over the years. In addition
to the well known GABAA receptor positive allosteric modulators (such as benzodiazepines and
barbiturate drugs), one can find antiparasitic drug such as ivermectin[18] and glutamate receptor
modulators used against Alzheimer's disease such as aniracetam.

Nicotinic receptor structure

In 1970, Changeux isolated the nicotinic acetylcholine receptor of
the eel electric organ, the first ever isolated membrane
pharmacological receptor,[20] that he was able to identify thanks to
the properties of a snake toxin, which was purified by Taiwanese
researchers CY Lee and CC Chang.[21] The isolation of the
receptor was also later reported by Ricardo Miledi.[22] The
improvements of purification methods developed in the group[23]
allowed the proposition that the receptor was a pentameric
protein,[24] a finding quickly confirmed by the team of Arthur
Karlin.[25] The group of Changeux was among the firsts to
Neurotransmitter acetylcholine
elucidate the primary structure of the subunits of the
bound to the nicotinic acetylcholine
receptor,[26][27] in parallel with the group of Shosaku Numa[28]
receptor. Adapted from[19]
and Stephen Heinemann.[29]

Throughout the 1980s and 1990s, molecular biology technics were used to decipher the tertiary and
quaternary structures of the receptor. The location of the ionic pore was identified, made up of the second
transmembrane segment,[30] as shown also later by the groups of Shosaku Numa[31] and Ferdinand
Hucho.[32] The molecular basis of ionic selectivity were also identified in the transmembrane
domain.[33][34][35] The structure of the binding site for the acetylcholine and nicotine was located at the
interface between adjacent subunits.[36][37][38]

The quest of Changeux for the structure of the nicotinic receptor culminated with the publication of the
structure, at atomic resolution, of a bacterial homolog in the open[39] and resting[40] conformations
supporting the concept of a symmetrical concerted opening for channel gating,[41] in agreement with
molecular dynamics simulations.[42][43]

Stabilization of synapses by neuronal activity

In 1973, together with Philippe Courrège and Antoine Danchin, Changeux proposed a model describing
how, during development of the nervous system, the activity of a network could cause the stabilization or
regression of the synapses involved[44] and illustrated it with the neuromuscular junction. This model is
effectively the precursor of the "neural Darwinism" theory further promoted by Gerald Edelman.
Changeux later extended and illustrated further this idea.[45] During the 1970s, he tried to document this
phenomenon, either by studying mutant animals[46][47] or by experimental denervation.[48][49]

Nicotinic receptor function

While until the 1990s, Changeux's group studied the structure of the nicotinic receptor present in electric
organs of electric eel and torpedo, the investigations of the physiological role of those receptors were
mostly focussed on two model systems: the nicotinic receptors of the neuromuscular junction, the
 synapse linking the motorneuron to the skeletal muscle, and the
nicotinic receptors of the brain, notably in relation with nicotine
addiction.

From the mid-1980s, the group studied the compartimentalisation of

the muscle cell upon development, as a model of synaptogenesis and
in relation with the theoretical work on epigenesis. In particular, the
group focussed on the accumulation of nicotinic receptors in the post-
synaptic region upon development, concomitant to a switch of
receptor identity. They were able to decrypt the different signalling
pathways involved in the response to synaptic activity, showing that
the accumulation resulted from an inhibition of gene transcription
outside the synaptic region due to electrical activity triggering an
uptake of calcium and activation of PKC,[50][51][52][53] and a
stimulation of gene transcription at the synapse by the calcitonin
Photo by Erling Mandelmann gene-related peptide (CGRP) activating PKA[54][55][56] and the ARIA
(heregulin) activating tyrosine kinase cascades.[57][58]

The 1990s saw the progressive shift of interest of Changeux from the neuromuscular junction to the
nicotinic receptors expressed in the brain. Among the notable achievements of the group is the discovery
that neuronal nicotinic receptors are highly permeable to calcium[59] – which explains the positive effect
of nicotinic receptors on the release of many neurotransmitters in the brain.[60]

The group also discovered that the nicotinic receptor is regulated by a variety of "allosteric modulators"
such as: 1. calcium ions[61] (This was also discovered independently by the group of John Dani[62]),
which binding sites were later identified[19][63] and localized in the extracellular domain, at the interface
between subunits (Le Novère et al. 2002); 2. ivermectin[18] which behaves as a potent positive allosteric
modulator binding to a site present in the transmembrane domain (where general anesthetics also
bind[64]); 3. phosphorylation of the cytoplasmic domain[65] which regulate desensitization.

By the mid-1990s, Changeux concentrated most of his interest on the function of nicotinic receptors in
the basal ganglia and in particular the mesencephalic dopaminergic system. Using mice deleted for
nicotinic receptor genes, the group characterised the types of receptor subunits present in the
dopaminergic cells[66][67][68] and identified the receptors mainly responsible of the dependence to
nicotine, formed by the subunits α4, α6 and β2.[69][70]

Modeling cognition
From the mid-1990s, Changeux developed an activity of computational modeling in order to investigate
the neuronal bases of cognitive functions. This research was mainly performed in collaboration with
Stanislas Dehaene, now leading the INSERM-CEA Cognitive Neuroimaging Unit. They notably modeled
the acquisition of song recognition in birds[71] and the development of numerical abilities.[72] More
recently, Dehaene and Changeux developed a neuronal model for access to consciousness based on a
brain-wide recruitment of networks of neurons with long-range axons, referred to as the global neuronal
workspace.[73][74] The model might have clinical applications for instance for understanding the
mechanism of coma, the action of general anesthetics[75] or drug addiction[76]

Professional and non-scientific activities

The publication of his book Neuronal Man: The Biology of The Mind in 1985 brought Changeux celebrity
status to the wider public. Since then, he authored or co-authored several other books inspired by his
teaching at the College de France: notably, Conversations on Mind Matter and Mathematics with the
mathematician Alain Connes (1998), What Makes Us Think with the philosopher Paul Ricoeur (2002) and
the Physiology of truth (2002) that are acknowledged as having initiated an instructive dialogue between
the two often-hostile disciplines of neuroscience and philosophy. He has also been concerned by the
relationships between aesthetic experience and the brain in Raison & Plaisir (1994), The true the good
the beautiful: a neurobiological approach (2012) and recently Les neurones enchantés. (2014) where he
debates the issue of artistic creation with the music composers Pierre Boulez and Philippe Manoury.
Changeux received the Lewis Thomas Prize for Writing about Science, Rockefeller University, New-
York, 2005.

Changeux has also been the curator of three major exhibitions on Art and Science: De Nicolo dell'Abate à
Nicolas Poussin: aux sources du Classicisme 1550-1650 Musée Bossuet Meaux in 1988, L'Âme au
Corps, Arts et Sciences, 1793-1993 (with Gérard Régnier) Galeries nationales du Grand Palais Paris in
1993-1994 and La lumière au siècle des Lumières et aujourd'hui. Art et science : de la biologie de la
vision à une nouvelle conception du monde Galeries Poirel Nancy in 2005. Changeux has also chaired the
inter-ministry commission for the conservation of the French artistic heritage since 1989, and has been
member of the scientific council of the International Agency of museums since 2007.

Last, throughout his career, Changeux has been concerned by the ethical consequences for the city and
for the society in general of the recent progress in the Neuroscience. Changeux has headed the National
Advisory Committee on Bioethics in France from 1992 to 1998. He organised a scientific conference on
the topic, that led to a book he edited, fondements naturel de l'ethique. He is presently the co-chairman of
the Ethics and Society division of the European Human Brain Program (since 2013).

He is also on the Board of Scientific Governors of The Scripps Research Institute, an independent not-for
profit biomedical research institute.

Public recognition

Main scientific prizes and awards

1978: Gairdner Foundation International Award
1982: Wolf Foundation Prize in Medicine
1982: Richard Lounsbery Award of the US Academy of Sciences and the French Academy
of Sciences
1991: Carl-Gustav-Bernhard medal of the Swedish Academy of Science
1992: CNRS Gold medal.
 1993: Louis-Jeantet Prize for Medicine
1994: Goodman and Gilman Award in drug receptor pharmacology
1995: Max Delbrück Medal
1998: Prize Emanuel Merck in Chemistry, Darmstadt
1999: ECNP Neuropsychopharmacology Award
2001: Balzan Prize for Cognitive Neurosciences
2002: American Philosophical Society's Karl Spencer Lashley Award in neuroscience
2005: Lewis Thomas Prize for Writing about Science
2005: Golden Eurydice Award
2007: NAS Award in the Neurosciences from the National Academy of Sciences[77]
2012: Japanese Society for the Promotion of Science (JSPS) award for eminent scientists
2016: International research award from the Olav Thon Foundation (Oslo)[78]
2018: Albert Einstein World Award of Science conferred by the World Cultural Council[79]
2018: Goldman-Rakic Prize for Outstanding Achievement in Cognitive Neuroscience[80]

Academic memberships and honorary degrees

Deutsche Akademie der Naturforscher Leopoldina zu Halle (Pharmacology), 1974; Académie de
Médecine de Turin, 1976; National Academy of Sciences, Washington (US) (foreign associate), 1983;
Royal Academy of Sciences, Stockholm, (Sweden) (foreign member), 1985; Académie des Sciences,
Paris, 1988; Académie Royale de Médecine de Belgique (Bruxelles) (foreign honorary member), 1988;
Academia Europaea (founding member), 1988; American Academy of Arts and Sciences, Boston, (US)
(foreign member), 1994; Romanian Academy of Medical Sciences, Bucarest (foreign member), 1996;
Institute of Medicine of the National Academies, Washington, (US) (foreign associate), 2000; Istituto
Veneto di Scienze, Lettere Ed Arti, Venezia (Italy), 2001; Hungarian Academy of Sciences, Budapest
(foreign member associate), 2004; European Academy of Sciences, Bruxelles (member), 2004;
International Academy of Humanism; Académie Royale des Sciences, des Lettres & des Beaux-Arts de
Belgique (foreign member), 2010; Accademia Nazionale dei Lincei, Rome, (Italy) (foreign member),
2010.

Doctor honoris causa : Universities of Torino, Italy, 1989; Dundee, Scotland, 1992; Geneva, Switzerland,
1994; Stockholm, Sweden, 1994; Liège, Belgium, 1996; Ecole Polytechnique Fédérale of Lausanne,
Switzerland, 1996; University of Southern California, Los Angeles, US, 1997; Bath, UK, 1997; Montréal
University, Canada, 2000; The Hebrew University of Jerusalem, Israel, 2004; Ohio State University,
Columbus, US, 2007; University of Buenos Aires, Argentina, 2010.

Honorary member of Neurosciences Research Program, MIT and Rockefeller University (US), since
1984; Honorary member of the Japanese Biochemical Society, Sendai, Japan, 1985; Honorary member of
the American Neurology Association, 1988; Honorary member of University College London, 1990;
Membre d'honneur à titre étranger de la Société Belge de Neurologie, Bruxelles, 1991; Member of
European Molecular Biology Organization.

Non-scientific honors
Grand Croix dans l'Ordre de la Légion d'Honneur, 2010; Grand-Croix dans l'Ordre National du Mérite
1995; Commandeur dans l'Ordre des Arts et des Lettres, 1994.

Scientific publications of historical significance

Monod, J.; Wyman, J.; Changeux, J. P. (1965). "On the Nature of Allosteric Transitions: A
Plausible Model". Journal of Molecular Biology. 12: 88–118. doi:10.1016/S0022-
2836(65)80285-6 (https://doi.org/10.1016%2FS0022-2836%2865%2980285-6).
PMID 14343300 (https://pubmed.ncbi.nlm.nih.gov/14343300). (in which Jacques Monod,
Jeffries Wyman and Jean-Pierre Changeux presented the concerted model of allosteric
transitions, that explained the cooperativity exhibited by many allosteric proteins, such as
hemoglobin)

Changeux J.-P., Kasai M., Huchet M., Meunier J.-C. (1970). Extraction à partir du tissu
électrique de gymnote d'une protéine présentant plusieurs propriétés caractéristiques du
récepteur physiologique de l'acétylcholine. C. R. Acad. Sci. 270D: 2864–2867. (the first
purification of a neurotransmitter receptor. Since the article is in French, most people quote
the description of the toxin that allowed the receptor to be identified: Changeux, J.; Kasai,
M.; Lee, C. (1970). "Use of a snake venom toxin to characterize the cholinergic receptor
protein" (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC283343). Proceedings of the
National Academy of Sciences of the United States of America. 67 (3): 1241–1247.
Bibcode:1970PNAS...67.1241C (https://ui.adsabs.harvard.edu/abs/1970PNAS...67.1241C).
doi:10.1073/pnas.67.3.1241 (https://doi.org/10.1073%2Fpnas.67.3.1241). PMC 283343 (htt
ps://www.ncbi.nlm.nih.gov/pmc/articles/PMC283343). PMID 5274453 (https://pubmed.ncbi.n
lm.nih.gov/5274453).
Changeux, J.; Courrège, P.; Danchin, A. (1973). "A theory of the epigenesis of neuronal
networks by selective stabilization of synapses" (https://www.ncbi.nlm.nih.gov/pmc/articles/P
MC427150). Proceedings of the National Academy of Sciences of the United States of
America. 70 (10): 2974–2978. Bibcode:1973PNAS...70.2974C (https://ui.adsabs.harvard.ed
u/abs/1973PNAS...70.2974C). doi:10.1073/pnas.70.10.2974 (https://doi.org/10.1073%2Fpn
as.70.10.2974). PMC 427150 (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC427150).
PMID 4517949 (https://pubmed.ncbi.nlm.nih.gov/4517949). (In which the authors develop a
formal model of synapse selection, precursor of the "neural darwinism". This is the original
work, although most people quote the subsequent review [better suited to a non-specialist
audience and presenting the biological context]: Changeux JP, Danchin A (1976) Nature,
264 (1976) 705–712.)

Books by Jean-Pierre Changeux

Changeux, Jean-Pierre. (2008) Du vrai, du beau, du bien : Une nouvelle approche
neuronale
Changeux, Jean-Pierre; Stuart Edelstein. (2004) Nicotinic Acetylcholine Receptors: From
Molecular Biology to Cognition
Changeux, Jean-Pierre. (2002) L'homme de verite (2004 The physiology of truth)
Changeux, Jean-Pierre; Paul Ricœur. (1998) Ce qui nous fait penser (2002 What Makes Us
Think. A Neuroscientist and a Philosopher Argue About Ethics, Human Nature, and the
Brain[81][82])
Changeux, Jean-Pierre. (1994) Raison et plaisir
Changeux, Jean-Pierre; Alain Connes. (1989) Matière à pensée (1995 Conversations on
Mind, Matter and Mathematics)
 Changeux, Jean-Pierre. (1983) L'homme neuronal (1985 Neuronal Man: The Biology of
Mind)

References
1. Louis-Jeantet Prize (https://www.jeantet.ch/en/prix-louis-jeantet/laureats/1993-en/professeur
-jean-pierre-changeux/)
2. The International Who's Who 2004 (https://books.google.com/books?id=sR4Ch1dMe8IC&p
g=PA299). Psychology Press. 2003. p. 299. ISBN 9781857432176.
3. Changeux J.-P. (1961). The feedback control mechanism of biosynthetic L-threonine
deaminase by L-isoleucine. Cold Spring Harbor. Symp. Quant. Biol. 26: 313-318.
4. Changeux J.-P. (1963). Allosteric Interactions on biosynthetic L-theonine deaminase from E.
coli K12. Cold Spring Harb Symp Quant Biol, 28: 497-504
5. Monod J., Changeux J.-P., and Jacob. F. (1963). Allosteric proteins and cellular control
systems. J. Mol. Biol. 6: 306-329
6. Monod J., Wyman J., and Changeux J.-P. (1965). On the nature of allosteric transitions: a
plausible model. J. Mol. Biol. 12: 88-118.
7. Rubin M.M., Changeux J.-P. (1966). On the nature of allosteric transitions; implications of
non-exclusive ligand binding. J. Mol. Biol. 21: 265-274.
8. Changeux J.-P., Thiéry J.-P., Tung Y., and Kittel C. (1967). On the cooperativity of biological
membranes. Proc. Natl. Acad. Sci. USA 57, 335-341.
9. Bray D, Levin MD, Morton-Firth CJ (1998) Receptor clustering as a cellular mechanism to
control sensitivity. Nature, 393: 85-88.
10. Changeux J.-P., Podleski T.R. (1968). On the excitability and cooperativity of electroplax
membrane. Proc. Natl. Acad. Sci. USA 59:944-950
11. Cartaud J., Benedetti E.L., Cohen J.B., Meunier J.C., Changeux J.-P. (1973) Presence of a
lattice structure in membrane fragments rich in nicotinic receptor protein from the electric
organ of Torpedo marmorata. FEBS Lett. 33: 109-113.
12. Weber M., David-Pfeuty M.T., Changeux J.-P. (1975). Regulation of binding properties of the
nicotinic receptor protein by cholinergic ligands in membrane fragments from Torpedo
marmorata. Proc. Natl. Acad. Sci. USA 72: 3443-3447.
13. Sugiyama H., Changeux J.-P. (1975). Interconversion between different states of affinity for
acetylcholine of the cholinergic receptor protein from Torpedo marmorata. Eur. J. Biochem.
55: 505-515.
14. Heidmann T., Changeux J.-P. (1979). Fast kinetic studies on the interaction of a fluorescent
agonist with the membrane-bound acetylcholine receptor from T. marmorata. Eur. J.
Biochem. 94: 255-279.
15. Edelstein S., Schaad O., Henry E., Bertrand D. Changeux J.-P. (1996). A kinetic mechanism
for nicotinic acetylcholine receptors based on multiple allosteric transitions. Biol. Cybern. 75:
361-379
16. Changeux J.-P. (2012). The concept of allosteric modulation: an overview. Drug Discov.
Today 10: e223-e228
17. Christopoulos, A; Changeux, J. P.; Catterall, W. A.; Fabbro, D; Burris, T. P.; Cidlowski, J. A.;
Olsen, R. W.; Peters, J. A.; Neubig, R. R.; Pin, J. P.; Sexton, P. M.; Kenakin, T. P.; Ehlert, F.
J.; Spedding, M; Langmead, C. J. (2014). "International Union of Basic and Clinical
Pharmacology. XC. Multisite pharmacology: Recommendations for the nomenclature of
receptor allosterism and allosteric ligands" (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1
1060431). Pharmacological Reviews. 66 (4): 918–47. doi:10.1124/pr.114.008862 (https://do
i.org/10.1124%2Fpr.114.008862). PMC 11060431 (https://www.ncbi.nlm.nih.gov/pmc/article
s/PMC11060431). PMID 25026896 (https://pubmed.ncbi.nlm.nih.gov/25026896).
18. Krause, R. M.; Buisson, B; Bertrand, S; Corringer, P. J.; Galzi, J. L.; Changeux, J. P.;
Bertrand, D (1998). "Ivermectin: A positive allosteric effector of the alpha7 neuronal nicotinic
acetylcholine receptor". Molecular Pharmacology. 53 (2): 283–94. doi:10.1124/mol.53.2.283
(https://doi.org/10.1124%2Fmol.53.2.283). PMID 9463487 (https://pubmed.ncbi.nlm.nih.gov/
9463487).
19. Le Novère N., Grutter T., Changeux J.-P. (2002). Models of the extracellular domain of the
nicotinic receptors and of agonist and Ca++ binding sites. Proc. Natl. Acad. Sci. USA, 99:
3210-3215.
20. Changeux J.-P., Kasai M., Huchet M., Meunier J.-C. (1970). Extraction à partir du tissu
électrique de gymnote d'une protéine présentant plusieurs propriétés caractéristiques du
récepteur physiologique de l'acétylcholine. C. R. Acad. Sci. 270D: 2864-2867.
21. Changeux J.-P., Kasai M., and Lee C.Y. (1970). The use of a snake venom toxin to
characterize the cholinergic receptor protein. Proc. Natl. Acad. Sci. USA 67: 1241-1247.
22. Miledi R., Molinoff P., Potter L.T. (1971). Isolation of the cholinergic receptor protein of
Torpedo electric tissue. Nature 229:554-557.
23. Olsen R., Meunier J.C., Changeux J.-P. (1972). Progress in purification of the cholinergic
receptor protein from Electrophorus electricus by affinity chromatography. FEBS Lett. 28.,
96-100.
24. Hucho F., Changeux J.-P. (1973). Molecular weight and quaternary structure of the
cholinergic receptor protein extracted by detergents from Electrophorus electricus electric
tissue. FEBS Lett. 38: 11-15
25. Weill C.L., McNamee M.G., Karlin A. (1974) Affinity-labeling of purified acetylcholine
receptor from Torpedo Californica. Biochem Biophys Res Comm 61: 997-1003.
26. Devillers-Thiéry A., Changeux J.-P., Paroutaud P., and Strosberg A.D. (1979). The amino-
terminal sequence of the 40.000 molecular weight subunit of the acetylcholine receptor
protein from Torpedo marmorata. FEBS Lett. 104: 99-105.
27. Devillers-Thiéry A., Giraudat J., Bentaboulet M., Changeux J.-P. (1983). Complete mRNA
coding sequence of the acetylcholine binding alpha subunit of Torpedo marmorata
acetylcholine receptor: a model for the transmembrane organization of the polypeptide
chain. Proc. Natl. Acad. Sci. USA 80: 2067-2071.
28. Noda M., Takahashi H., Tanabe T., Toyosato M., Furutani Y., Hirose T., Asai M., Inayama S.,
Miyata T., Numa S. (1982) Primary structure of alpha-subunit precursor of Torpedo
californica acetylcholine receptor deduced from cDNA sequence. Nature 299:793-797.
29. Ballivet M., Patrick J., Lee J., Heinemann S. (1982) Molecular cloning of cDNA coding for
the gamma subunit of Torpedo acetylcholine receptor. Proc Natl Acad Sci U S A. 79:4466-
4470.
30. Giraudat J., Dennis M., Heidmann T., Chang J.Y., Changeux J.-P. (1986). Structure of the
high affinity site for noncompetitive blockers of the acetylcholine receptor: serine-262 of the
delta subunit is labeled by [3H]-chlorpromazine. Proc. Natl. Acad. Sci. USA 83: 2719-2723.
31. Imoto K., Methfessel C., Sakmann B., Mishina M., Mori Y., Konno T., Fukuda K., Kurasaki
M., Bujo H., Fujita Y., Shosaku N. (1986). Location of a delta-subunit region determining ion
transport through the acetylcholine receptor channel. Nature. 1986 Dec 18-
31;324(6098):670-4.
32. Hucho F., Oberthür W., Lottspeich F. (1986) The ion channel of the nicotinic acetylcholine
receptor is formed by the homologous helices M II of the receptor subunits. FEBS Lett.205:
137-142.
33. Galzi J.-L., Devillers-Thiery A., Hussy N., Bertrand S., Changeux J.-P., Bertrand D. (1992).
Mutations in the ion channel domain of a neuronal nicotinic receptor convert ion selectivity
from cationic to anionic. Nature 359: 500-505.
34. Bertrand D., Galzi J.-L., Devillers-Thiéry A., Bertrand S., Changeux J.-P. (1993). Mutations
at two distinct sites within the channel domain M2 alter calcium permeability of neuronal
alpha7 nicotinic receptor. Proc. Natl. Acad. Sci. USA 90: 6971-6975.
35. Corringer P.-J., Bertrand S., Galzi J.-L., Devillers-Thiéry A., Changeux J.-P., Bertrand D.
(1999). Mutational Analysis of the Charge Selectivity Filter of the a7 Nicotinic Acetylcholine
Receptor. Neuron 22: 831-843.
36. Dennis M., Giraudat J., Kotzyba-Hibert F., Goeldner M., Hirth C., Chang J.Y., Lazure C.,
Chrétien M., Changeux J.-P. (1988). Amino acids of the Torpedo marmorata acetylcholine
receptor subunit labeled by a photoaffinity ligand for the acetylcholine binding site.
Biochemistry 27: 2346-2357.
37. Galzi J.-L., Revah F., Black D., Goeldner M., Hirth C., Changeux J.-P. (1990). Identification
of a novel amino acid a-Tyr 93 within the active site of the acetylcholine receptor by
photoaffinity labeling: additional evidence for a three-loop model of the acetylcholine binding
site. J. Biol. Chem. 265: 10430-10437.
38. Galzi J.-L., Bertrand D., Devillers-Thiéry A., Revah F., Bertrand S., Changeux J.-P. (1991).
Functional significance of aromatic amino acids from three peptide loops of the alpha 7
neuronal nicotinic receptor site investigated by site-directed mutagenesis. FEBS Lett. 294:
198-202.
39. Bocquet N., Nury H., Baaden M., Le Poupon C., Changeux J.-P., Delarue M., Corringer P.-J.
(2009) X-ray structure of a pentameric ligand-gated ion channel in an apparently open
conformation. Nature 457(7225):111-114
40. Sauguet, L; Shahsavar, A; Poitevin, F; Huon, C; Menny, A; Nemecz, A.; Haouz, A;
Changeux, J. P.; Corringer, P. J.; Delarue, M (2014). "Crystal structures of a pentameric
ligand-gated ion channel provide a mechanism for activation" (https://www.ncbi.nlm.nih.gov/
pmc/articles/PMC3903189). Proceedings of the National Academy of Sciences. 111 (3):
966–71. Bibcode:2014PNAS..111..966S (https://ui.adsabs.harvard.edu/abs/2014PNAS..11
1..966S). doi:10.1073/pnas.1314997111 (https://doi.org/10.1073%2Fpnas.1314997111).
PMC 3903189 (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3903189). PMID 24367074
(https://pubmed.ncbi.nlm.nih.gov/24367074).
41. Hilf R.J., Dutzler R. (2009) Structure of a potentially open state of a proton-activated
pentameric ligand-gated ion channel. Nature 457(7225):115-118
42. Taly A., Delarue M., Grutter T., Nilges M., Le Novère N., Corringer P.-J., Changeux J.-P.
(2005) Normal mode analysis suggests a quaternary twist model for the nicotinic receptor
gating mechanism. Biophys. J. 88:3954-3965
43. Calimet N., Simoes M., Changeux J.-P., Karplus M., Taly A., Cecchini M. (2013) From the
Cover: A gating mechanism of pentameric ligand-gated ion channels. Proc Natl Acad Sci U
S A. 110:E3987-3996
44. Changeux J.-P., Courrège P., Danchin A. (1973). A theory of the epigenesis of neural
networks by selective stabilization of synapses. Proc. Natl. Acad. Sci. USA 70: 2974-2978.
45. Changeux J.-P., Danchin, A. (1976). Selective stabilization of developing synapses as a
mechanism for the specification of neuronal networks. Nature 264: 705-712.
46. Sotelo C., Changeux J.-P. (1974). Transsynaptic degeneration 'en cascade' in the cerebellar
cortex of staggerer mutant mice. Brain Res. 67: 519-526.
47. Mariani J., Crepel F., Mikoshiba K., Changeux J.-P. (1977). Anatomical, physiological and
biochemical studies of the cerebellum from reeler mutant mouse. Phyl. Trans. Royal Soc. B
281: 1-28
48. Benoit P, Changeux J.P. (1975) Consequences of tenotomy on the evolution of
multiinnervation in developing rat soleus muscle. Brain Res.99:354-8
49. Henderson CE, Huchet M, Changeux JP. Denervation increases a neurite-promoting activity
in extracts of skeletal muscle. Nature. 1983 Apr 14;302(5909):609-11.
50. Betz H., Changeux J.-P. (1979). Regulation of muscle acetylcholine receptor synthesis in
vitro by cyclic nucleotide derivatives. Nature 278: 749-752.
51. Klarsfeld A., Changeux J.-P. (1985). Activity regulates the level of acetylcholine receptor
alpha-subunit mRNA in cultured chick myotubes. Proc. Natl. Acad. Sci. USA 82: 4558-4562.
52. Klarsfeld A., Laufer R., Fontaine B., Devillers-Thiéry A., Dubreuil C., Changeux J.-P. (1989).
Regulation of muscle AChR alpha-subunit gene expression by electrical activity :
involvement of protein kinase C and Ca++. Neuron 2: 1229-1236.
53. Piette J., Bessereau J.-L., Huchet M., Changeux J.-P. (1990). Two adjacent MyoD1-binding
sites regulate the expression of the acetylcholine receptor delta-subunit gene. Nature 345:
353-355.
54. Fontaine B., Klarsfeld A., Hokfelt T., Changeux J.-P. (1986). Calcitonin gene-related peptide,
a peptide present in spinal cord motoneurons, increases the number of acetylcholine
receptors in primary cultures of chick embryo myotubes. Neurosci. Lett. 71: 59-65.
55. Fontaine B., Klarsfeld A., Changeux J.-P. (1987). Calcitonin-gene related peptide and
muscle activity regulate acetylcholine receptor alpha-subunit mRNA levels by distinct
intracellular pathways. J. Cell Biol. 105: 1337-1342.
56. Laufer R., and Changeux J.-P. (1987). Calcitonin gene-related peptide elevates cyclic AMP
levels in chick skeletal muscle : possible neurotrophic role for a coexisting neuronal
messenger. EMBO J. 6: 901-906.
57. Altiok N., Bessereau J.-L., Changeux J.-P. (1995). ErB3 and ErbB2/neu mediate the effect of
heregulin on acetylcholine receptor gene expression in muscle : differential expression at
the endplate. EMBO J. 14: 4258-4266.
58. Schaeffer L., Duclert N., Huchet-Dymanus M., Changeux J.-P. (1998). Implication of a
multisubunit Ets related transcription factor in synaptic expression of the nicotinic
acetylcholine receptor. EMBO J., 17: 3078-3090.
59. Mulle C., Choquet D., Korn H., Changeux J.-P. (1992). Calcium influx through nicotinic
receptor in rat central neurons : Its relevance to cellular regulation. Neuron 8: 135-143.
60. Léna C, Changeux, JP (1997). Role of Ca2+ ions in nicotinic facilitation of GABA release in
mouse thalamus. J Neurosci 17: 576-585.
61. Mulle C., Léna C., Changeux J.-P. (1992). Potentiation of nicotinic receptor response by
external calcium in rat central neurons. Neuron 8: 937-945.
62. Vernino S, Amador M, Leutje CW, Patrick J, and Dani JA (1992) Calcium modulation and
high calcium permeability of neuronal nicotinic acetylcholine receptors. Neuron 8: 127-134
63. Galzi J.-L., Bertrand S., Corringer P.-J., Changeux J.-P., Bertrand D. (1996). Identification of
calcium binding sites that regulate potentiation of a neuronal nicotinic acetylcholine receptor.
EMBO J. 15: 5824-5832.
64. Nury H., Van Renterghem C., Weng Y., Tran A., Baaden M., Dufresne V., Changeux J.-P.,
Sonner J.M., Delarue M., Corringer P.-J. (2011) X-ray structures of general anaesthetics
bound to a pentameric ligand-gated ion channel. Nature 469(7330):428-431
65. Teichberg V.I., Sobel A., Changeux J.-P. (1977) In vitro phosphorylation of the acetylcholine
receptor. Nature 267(5611):540-542
66. Le Novère N., Zoli M., Changeux J.-P. (1996). Neuronal nicotinic receptor a6 subunit mRNA
is selectively concentrated in catecholaminergic nuclei of the rat brain. Eur J Neurosci 8:
2428-2439
67. Klink R., de Kerchove d'Exaerde A., Zoli M., Changeux J.-P. (2001). Molecular and
Physiological Diversity of Nicotinic Acetylcholine Receptors in the Midbrain Dopaminergic
Nuclei. J. Neurosci. 21: 1452-1463.
68. Champtiaux N, Gotti C, Cordero-Erausquin M, David DJ, Przybylski C, Lena C, Clementi F,
Moretti M, Rossi FM, Le Novere N, McIntosh JM, Gardier AM, Changeux JP (2003) Subunit
composition of functional nicotinic receptors in dopaminergic neurons investigated with
knock-out mice. J Neurosci., 2003 Aug 27;23(21):7820-9.
69. Picciotto M.R., Zoli M., Rimondini R., Léna C., Marubio L., Merlo Pich E., Fuxe K.,
Changeux J.-P. (1998). Acetylcholine receptors containing the b2-subunit are involved in the
reinforcing properties of nicotine. Nature 391: 173-177 (1998).
70. Maskos U., Molles B.E, Pons S., Besson M., Guiard B.P., Guilloux J.P., Evrard A., Cazala P.,
Cormier A., Mameli-Engvall M., Dufour N., Cloz-Tayarani I., Bemelmans A.-P., Mallet J.,
Gardier A.M., David V., Faure P., Granon S. and Changeux J.-P. (2005) Nicotine
reinforcement and cognition restored by targeted expression of nicotinic receptors. Nature
436: 103-107
71. Dehaene S., Changeux J.-P., Nadal J.P. (1987). Neural networks that learn temporal
sequences by selection. Proc. Natl. Acad. Sci. USA 84: 2727-2731.
72. Dehaene S., Changeux J.-P. (1993). Development of elementary numerical abilities : a
neuronal model. J. Cognitive Neurosci 5: 390-407.
73. Dehaene S., Kerszberg M., Changeux J.-P. (1998). A neuronal model of a global workspace
in effortful cognitive tasks. Proc Natl Acad Sci USA 95: 14529-14534.
74. Dehaene S., Sergent C., Changeux J.-P. (2003) A neuronal network model linking subjective
reports and objective physiological data during conscious perception. Proc. Natl. Acad. Sci.
USA, 100: 8520-8525.
75. Changeux J.-P. (2012) Conscious processing: implications for general anesthesia. Curr.
Opin. Anesthesiol. 25:397–404.
76. Changeux J.-P., Lou H.C. (2011) Emergent pharmacology of conscious experience: new
perspectives in substance addiction. FASEB J. 25(7):2098-2108.
77. "NAS Award in the Neurosciences" (https://web.archive.org/web/20101229195610/http://ww
w.nasonline.org/site/PageServer?pagename=AWARDS_neurosciences). National Academy
of Sciences. Archived from the original (http://www.nasonline.org/site/PageServer?pagenam
e=AWARDS_neurosciences) on 29 December 2010. Retrieved 16 February 2011.
78. "International research award from the Olav Thon Foundation 2016" (http://www.uio.no/engli
sh/about/news-and-events/news/2016/the-olav-thon-foundation.html). Retrieved 28 April
2016.
79. "Le prix Albert-Einstein World Award of Science 2018 est remis à Jean-Pierre Changeux" (ht
tps://www.college-de-france.fr/site/jean-pierre-changeux/Le-prix-Albert-Einstein-2018-est-re
mis-a-Jean-Pierre-Changeux.htm) (in French). Collège de France. 4 June 2018. Retrieved
3 July 2018.
80. "Jean-Pierre Changeux, PhD" (https://www.bbrfoundation.org/about/people/jean-pierre-chan
geux-phd). 29 October 2018.
81. Review of What Makes Us Think by Howard Gardner (http://www.pages.drexel.edu/~pa34/w
hatmakesusthink.htm) Archived (https://web.archive.org/web/20050216170739/http://www.p
ages.drexel.edu/~pa34/whatmakesusthink.htm) 16 February 2005 at the Wayback Machine
82. Review of What Makes Us Think by Elliott White (http://www.politicsandthelifesciences.org/
Contents/Contents-2000-9/PLS2000-9-269.pdf) Archived (https://web.archive.org/web/2006
0322073832/http://www.politicsandthelifesciences.org/Contents/Contents-2000-9/PLS2000-
9-269.pdf) 22 March 2006 at the Wayback Machine

External links
Jean-Pierre Changeux (https://scholar.google.com/citations?user=Bq3F8iIAAAAJ)
publications indexed by Google Scholar
Jean-Pierre Changeux's laboratory in 2005 (https://web.archive.org/web/20130203182959/h
ttp://www.pasteur.fr/recherche/RAR/RAR2005/Neubio.html)
Jean-Pierre Changeux (http://www.balzan.org/en/prizewinners/jean-pierre-changeux)
International Balzan Prize Foundation

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