François Clarac

Jean-Gaël Barbara

Emmanuel Broussolle

Jacques Poirier

François Félix Vicq D'azyr

Xavier Bichat

Franz Joseph Gall

Jean Cruveilhier

Jules Bernard Luys

Paul Broca

Louis Ranvier

André Victor Cornil

Albert Gombault

Jean Nageotte

René Couteaux

à 1950. Introduction et Partie I: Neuroanatomie

Keywords: histoire, Paris, neurosciences, anatomie, physiologie, neurology, psychiatrie, psychologie physiologie, neurologie, et psychiatrie-psychologie

à la diffusion de documents scientifiques de niveau recherche, publiés ou non, émanant des établissements d'enseignement et de recherche français ou étrangers, des laboratoires publics ou privés.

Introduction

During the last decades, neuroscience research has experienced a tremendous growth in many fields of interest, notably in the anatomical, physiological, neurological or psychiatric domains. However, most of today's young scientists and physicians do not have sufficient historical background of these fascinating disciplines. Numerous authors from many parts of the world contributed to the development of the neurosciences and particularly neurology [START_REF] Clarac | History of Neurology in France[END_REF][START_REF] Clarac | Encyclopédie historique des Neurosciences. Du neurone à l'émergence de la pensée[END_REF][START_REF] Finger | Origins of Neuroscience: A history of explorations into brain function[END_REF][START_REF] Finger | Minds Behind the Brain: A History of the Pioneers and their Discoveries[END_REF][START_REF] Haymaker | The Founders of neurology, one hundred and thirty-three biographical sketches prepared for the fourth International neurological congress in Paris[END_REF][START_REF] Rancurel | Les noms en neurologie[END_REF]. As early as the XIX th century, special credit should be given to German speaking universities from Central Europe, institutions in Great Britain and North America, French and Italian neurological schools, and also medical universities from Belgium, the Netherlands, Scandinavia, Southern Europe, Russia and subsequently from South America, Asia and Africa during the XX th century.

We took the opportunity of the XV th Annual Meeting of the International Society for the History of the Neurosciences, held in Paris in June 2010, to prepare a historical work in order to make a short presentation of the major institutions and figures who contributed to make Paris a renowned centre of physiology and neurology between the XIX th and the first half of the XX th century. We purposely chose to focus on the period 1800-1950, as 1800 corresponds to the actual beginning of neurosciences, and 1950 marks its rise.

The beginning of the XIX th century in France was characterized by a remarkable improvement of the medical and physiological knowledge. This was due to the influence of several combined factors. First, the XVIII th century Enlightenment and the Mouvement Encyclopédique (Encyclopedic Movement), with an emerging scientific approach of philosophy (positivism and materialism). Second, the French Revolution, with marked restructuring of the French hospital system (establishment of internship/residentship and externship in 1802) and of the academic organization (re-foundation of the three Écoles de Santé -Medical facultiesin 1794). Third, the simultaneous presence of exceptional figures as François de Fourcroy (1715-1809), Pierre-Jean Georges Cabanis (1757[START_REF] Spurzheim | Recherches sur le système nerveux en général et sur celui du cerveau en particulier, mémoire présenté à l'Institut de France[END_REF] and Philippe Pinel (1745-1826) to name but a few among the pioneers.

In 1830, there were numerous hospitals in Paris, in which 5 000 medical students were working and where more than 20 000 patients were treated. Three medical faculties were developed at that time, in Paris, Montpellier and Strasbourg, respectively. The other major cities such as Lyon, Marseille, Bordeaux, Lille or Toulouse only had medical schools which did not become faculties of their own right before the end of XIX th century and the beginning of the XX th century.

To put it shortly, the XIX th century in France -in what regards the scientific domain -was deeply marked by two major conflicting ideologies. As illustrated by Cabanis in his Rapport du physique et du moral (Essay on Body and Mind) published in 1802 in which he considered that "le cerveau sécrète la pensée comme le foie sécrète la bile" (the brain secretes the thought, just like the liver secretes bile) (Cabanis et al., 1802), the materialists claimed that the human psyche was to be understood uniquely with the help of physiology. They adopted the positivism of Auguste Comte (1798-1857) and his denial of the spiritualist psychology. Just like Émile Zola's (1840-1902) Docteur Pascal, they were convinced that the advances of Science would bring happiness to the world (Zola, 1893). On the opposite, conservativeswho had the support of the royalist side and religious authoritiesfollowed the ideas of Descartes and defended the body-mind dualism.

We have limited this presentation to Paris and its surroundings because the French capital, unlike in other cities, have long been the focal point of the country. After the reigns of Louis XIV and of Napoléon, everything was centralized in Paris, thus giving only a minor role to other cities. This explains why many of the figures we are going to evoke in this article "went up" to Paris, in search of a successful career. Our presentation will be divided into four chapters, matching the four disciplines which have progressed and contributed the most to the knowledge we have of the brain sciences: anatomy, physiology, neurology, and psychiatry-psychology.

Part I. Neuroanatomy

In the XIX th century, the anatomical studies concerning the nervous system were mainly dedicated to first the neuron, second the cerebral cortex.

The nerve cell -which was termed the neuron in the 1890s by Heinrich Wilhelm Gottfried von Waldeyer-Hartz (1836-1921) after the work of Santiago Ramón y Cajal (1852-1934), Wilhelm His (1831-1904) and August Henri Forel (1848-1931) -appeared to have the same essential characteristics as all the other cells of the living beings despite its particularities, thus confirming the cellular theory that had already been enounced in 1839 by two other German biologists Theodor Schwann (1810-1882) and Matthias Schleiden (1804Schleiden ( -1881)).

Earlier, in the first half of the XIX th century, two French anatomists François Leuret (1797Leuret ( -1851)), psychiatrist and student of Jean-Etienne Esquirol (1772-1840), and zoologist Pierre Gratiolet (1815-1865) took major steps forwards in our knowledge of the cortex. The fundamental data from their work Anatomie comparée du système nerveux (Comparative Anatomy of the Nervous System) allowed an accurate localization of the different areas of the brain. Leuret defined lobes and gyri as primary points of comparative anatomy on which are based the psychic functions (Leuret, 1857a(Leuret, , 1857b)). Gratiolet complemented the results of his colleague by describing five lobes (frontal, parietal, temporal, occipital and insular) in each cerebral hemisphere, and the optic radiations that allow the connexion between the thalamus and the visual cortex [START_REF] Gratiolet | Observations sur le poids et la forme du cerveau, lues à la Société d'anthropologie[END_REF]. In 1840, the French psychiatrist Jules Gabriel François Baillarger (1809Baillarger ( -1890) ) brought to light six cortical layers -in turn transparent or opaque -while working on thin sections of the cortex with a microscope (Baillarger, 1840). This stratification has been adopted and enhanced outside France by Robert Remak (1815Remak ( -1865) ) (Remak, 1838(Remak, , 1841(Remak, , 1847) ) and Albert von Kölliker (1817Kölliker ( -1905) ) in 1841 and 1850, respectively [START_REF] Kölliker | Mikroskopische anatomie, oder, Gewebelehre des menschen[END_REF][START_REF] Eulenburg | Die Krankheiten des Nervensystems[END_REF]. These works on the brain led to intense arguments between the localisationists, who claimed that each area of the brain had its own function, and the unitarians who thought that the whole brain achieved all the functions. During the XIX th century, French histologists were going to Germany to learn the different new techniques, in particular in the laboratory of Rudolf Virchow (1821Virchow ( -1902)). However, with Louis Ranvier (1835Ranvier ( -1922) ) and its great anatomical influence, anatomy and histology became very potent disciplines, a real school was started in Paris, and continued with René [START_REF] Tsuji | -1999) and the morphological identification of synapses[END_REF]Couteaux ( -1999)), Jacques Taxi and André Calas. Following this introductory paragraph on the scientific context of the time, we will now present -without being exhaustive -a biographical sketch of several scientists who worked in Paris and greatly contributed to our knowledge of brain anatomy.

Félix Vicq d'Azyr (1746-1794) Born in Normandy, Vicq d'Azyr (Figure 1) [START_REF] Farrell | Fragments of neurologic history: Félix Vicq d'Azyr and neuroanatomy[END_REF][START_REF] Goldblatt | The key to the brain. Félix Vicq d'Azyr (1748-1794)[END_REF][START_REF] Hannaway | Vicq d'Azyr, anatomy and a vision of medicine[END_REF][START_REF] Mandressi | The past, education and science. Félix Vicq d'Azyr and the history of medicine in the 18 th century[END_REF][START_REF] Mercado | Vascular anatomy of the foramen of Vicq d'Azyr: a microsurgical perspective[END_REF][START_REF] Parent | Vicq d'Azyr: anatomy, medicine and revolution[END_REF][START_REF] Sournia | Félix Vicq d Azyr, inventeur de l'Académie de Médecine (1748-1794)[END_REF][START_REF] Stafford | Depth studies: illustrated anatomies from Vesalius to Vicq d'Azyr[END_REF][START_REF] Van Gijn | Félix Vicq d'Azyr (1748-1794)[END_REF] studied medicine in Paris and was the protégé of Antoine Petit (1722-1794), a professor of anatomy at the former Jardin du Roi (King's garden), current Jardin des Plantes (Paris Botanical garden). Vicq d'Azyr, a person of poor health, returned to Normandy in 1773, where he studied fish. After the publication of his work, and with the support of two of his masters, Marie Jean Antoine Nicolas de Caritat, Marquis de Condorcet (1743-1794) and Louis Daubenton (1715-1799), he became a member of the Académie des Sciences (French Academy of Sciences) in 1774. In the same year, he was given the responsibility of analyzing a severe "cattle epizootic" by the Contrôleur des Finances (finance Minister) Anne-Robert Turgot (1727-1781) [START_REF] Meynell | Vicq d'Azyr and a cattle plague[END_REF]. He travelled across the French provinces and made suggestions to avoid the propagation of this epidemic. His report led Jacques Necker (1732-1804)the successor of Turgot to create the Société Royale de Médecine (Royal Society of Medicine), in charge of analyzing diseases and their treatments throughout the kingdom, society of which he became the perpetual secretary and Joseph Marie François Lassone (1717-1788) the president. Vicq d'Azyr contributed fundamentally to the study of anatomy and especially human brain anatomy (Vicq d'Azyr, s.d., 1779[START_REF] Vicq D'azyr | Mémoire sur la description des nerfs de la seconde et troisième paire cervicale[END_REF], 1784, 1786a[START_REF] Vicq D'azyr | Oeuvres complètes. Textes recueillis par Jacques Louis Moreau de la Sarthe[END_REF]. In 1786, Vicq d'Azyr published his Traité d'anatomie comparée et de physiologie (Treatise on Comparative Anatomy and Physiology), a remarkable anatomy and physiology treatise illustrated by sections of the human brain of a quality and exactitude never attained before (Vicq d'Azyr, 1786b, 1786c). He presented the deep brain structures and was the first one to describe the locus coeruleus, the locus niger and the mammillothalamic tract, also known as bundle of Vicq d'Azyr. We owe him the concept "homology" in biology. During the French Revolution, he presented a decisive plan to reform the teaching of medicine in France, and encouraged François de Fourcroy to have the three Écoles de Santé (Medical Faculties) re-created, in Paris, Montpellier and Strasbourg voted by the convention in 1794 [START_REF] Peumery | Vicq d'Azyr et la Révolution Française[END_REF] .

François Xavier Bichat (1771Bichat ( -1802) ) Bichat (Figure 2) was born in Thoirette in the Jura French département (County) and trained in medicine in Lyon under the guidance of the young surgeon Marc-Antoine Petit (1766-1811). He joined the Army of the Alps as a surgeon during the French Revolution. In 1794 he collaborated with Pierre Desault (1738-1795) at the Hôtel-Dieu hospital in Paris, until the sudden death of Desault which left Bichat alone, when aged 24. He compiled and published in a single piece of work, the lessons taught by his two masters and was appointed chief surgeon at the Hôtel-Dieu hospital, when he was only 29. In 1796, he founded the Société Médicale d'Émulation (Medical Society of Emulation), one of the most prestigious scientific associations of that time. Bichat investigated the pathology of diseases [START_REF] Albury | Experiment and explanation in the physiology of Bichat and Magendie[END_REF]Anonymous, 1968b[START_REF] Anonymous | Marie François Xavier Bichat 1771-1802[END_REF][START_REF] Baudet | Xavier Bichat (1771-1802[END_REF][START_REF] Binet | A la gloire d'un grand médecin: Xavier Bichat (1771-1801)[END_REF]Breathnach, 1981a;[START_REF] Elaut | The theory of membranes of F. X. Bichat and his predecessors[END_REF][START_REF] Fye | Marie-François-Xavier Bichat[END_REF][START_REF] Godlewski | [END_REF][START_REF] Haas | Marie François Xavier Bichat (1771-1802[END_REF][START_REF] Haigh | The roots of the vitalism of Xavier Bichat[END_REF][START_REF] Haigh | Xavier Bichat and the medical theory of the eighteenth century[END_REF][START_REF] Heywood | s "blood consciousness" and the work of Xavier Bichat and Marshall Hall[END_REF][START_REF] Mcintyre | Xavier Bichat (1771-1802[END_REF][START_REF] Prichard | Selected items from the history of pathology: Marie-François-Xavier Bichat (1771-1802)[END_REF][START_REF] Shoja | Marie-François Xavier Bichat (1771-1802) and his contributions to the foundations of pathological anatomy and modern medicine[END_REF]. Gaspard Laurent Bayle (1774-1816), René Théophile Laënnec (1781-1826) and Guillaume Dupuytren (1777-1835), three students of Bichat, members of this Society, founded the famous anatomo-clinical School of Paris (Anonymous, 1968a). At the same time Bichat began to give private lectures on anatomy and operative surgery. He published several major treatises such as Le Traité des membranes (A Treatise on the Membranes), in July 1799 (Bichat, 1799). He soon after attempted to explain the passage from life to death with anatomical, physiological and pathological analyses, by observing the way the different organs of the human body interact, in Recherches physiologiques sur la vie et la mort (Physiological Researches on Life and Death) in which he opposed the notion of vie de relation (animal life) to the one of vie végétative (organic life) [START_REF] Bichat | Recherches physiologiques sur la vie et la mort[END_REF]. In his Traité d'anatomie générale appliquée à la physiologie et à la médecine (General Anatomy Applied to Physiology and Medicine) published in 1801, he defined the notion of tissue by dividing organs into 21 elementary tissues, by dissection and without using a microscope [START_REF] Bichat | Anatomie générale, appliquée à la physiologie et à la médecine[END_REF].

Franz Joseph [START_REF] Ellis | -1828): false prophet of cerebral localization[END_REF]Gall ( -1828) ) German physician and anatomist, Gall (Figure 3) first studied medicine at the university of Strasbourg and then at the university of Vienna. He became a professor and a brilliant neuroanatomist [START_REF] Critchley | Neurology's debt to F. J. Gall (1758-1828[END_REF][START_REF] Ellis | -1828): false prophet of cerebral localization[END_REF][START_REF] Kaitaro | Biological and epistemological models of localization in the nineteenth century: from Gall to Charcot[END_REF][START_REF] Lechtenberg | [END_REF][START_REF] Lesky | Structure and function in Gall[END_REF][START_REF] Livianos-Aldana | Gall and the phrenological movement[END_REF][START_REF] Macmillan | Inhibition and the control of behavior. From Gall to Freud via Phineas Gage and the frontal lobes[END_REF][START_REF] Pardue | Joseph Gall-pioneering nuclear biology[END_REF][START_REF] Rawlings | Franz Josef Gall and his contribution to neuroanatomy with emphasis on the brain stem[END_REF][START_REF] Simpson | Phrenology and the neurosciences: contributions of F. J. Gall and J.G. Spurzheim[END_REF][START_REF] Van Wyhe | The authority of human nature: the Schädellehre of Franz Joseph Gall[END_REF][START_REF] Young | The functions of the brain: Gall to Ferrier (1808-1886)[END_REF][START_REF] Le Docteur Pascal | Localization of brain function: the legacy of Franz Joseph Gall (1758-1828)[END_REF]. Gall invented a new method of dissecting the brain, which helped him to make great progresses in the understanding of brain function [START_REF] Spurzheim | Recherches sur le système nerveux en général et sur celui du cerveau en particulier, mémoire présenté à l'Institut de France[END_REF](Gall, , 1822a(Gall, , 1822b(Gall, , 1823a(Gall, , 1823b(Gall, , 1825[START_REF] Gall | Précis du système phrénologique du docteur Gall[END_REF]. He supported the idea that psychic functions have a concrete localization within the brain. He was expelled from Austria and he subsequently came to France where his theories met a great success, despite being invalidated by the Académie des Sciences. Gall coined the term cranioscopy, name he gave to his method of attempting to associate the different gyri of the surface of the cortex with psychic properties, but his main disciple Johann Christoph Spurzheim (1766Spurzheim ( -1833) ) renamed it phrenology in 1810 (Spurzheim and Gall, 1809), term still used today. He distinguished 27 mental faculties at the surface of the brain, which he stratified into 3 groups:

-The first one is shared by all the vertebrates and is located in the posterior and lower parts of encephalon and includes: « l'instinct de propagation, l'amour de la progéniture, l'attachement et l'amitié, le goût pour les rixes et les combats, le penchant pour le meurtre, le penchant pour la ruse, le sentiment de propriété…. » ('the reproduction instinct, the love of one's offspring, attachment and friendship, the taste for fighting and brawl, the tendency to murder and cunning, and the feeling of property").

-The second, found in higher vertebrates, is located in the inferior part of the anterior lobes. There are to be found "la mémoire des choses et des faits, le sens des localités et des rapports dans l'espace, la mémoire des personnes, le sens des mots et des noms, la mémoire verbale, le sens du langage et de la parole" ("the memory of facts and things, the sense of places and space proportions, the memory of persons, the sense of words and names, the verbal memory and the sense of language and speech").

-The third group is proper to humans and is located in the upper part of the anterior lobes (prefrontal area). It includes "la sagesse comparative, l'esprit métaphysique et la profondeur de l'esprit…" ("the comparative sagacity, the sense of metaphysics and the depth of the mind").

Despite the examination of hundreds of brains and skulls, phrenology does not have a scientific backing, as the correlations it pretends to establish between anatomy and behavioural observation remain very subjective. Harshest criticism of phrenology originated from Marie Jean Pierre Flourens (see Neurophysiology chapter).

Jean Cruveilhier (1791Cruveilhier ( -1874) ) Jean Cruveilhier (Figure 4), was born in Limoges in the center of France [START_REF] Androutsos | The eminent French pathologist Jean Cruveilhier (1791-1874) and his works on cancer[END_REF][START_REF] Anonymous | Eponym: Cruveilhier-Baumgarten syndrome[END_REF][START_REF] Bakay | Cruveilhier on meningiomas (1829-1842)[END_REF][START_REF] Flamm | The neurology of Jean Cruveilhier[END_REF][START_REF] Pearce | Cruveilhier and acoustic neuroma[END_REF][START_REF] Tainmont | A historical vignette (14). The anatomo-clinical method applied to ENT at the time of Jean Cruveilhier[END_REF][START_REF] Waring | William Middleton Michel in Paris, 1842-1846. A vignette of Cruveilhier[END_REF]. He made a career in Paris with the support of the famous surgeon Guillaume Dupuytren (1777-1835) [START_REF] Orcel | Dupuytren, Cruveilhier and the anatomical society[END_REF]. In 1826 he reinstated the Société anatomique (Anatomical Society) that had been dissolved in 1808, and was appointed médecin des hôpitaux de Paris (senior physician of Paris hospitals) and then became head of a department of medicine at La Salpêtrière hospital the same year. In 1825 he was appointed professor of anatomy at the Paris Faculty of Medicine and became in 1835 the first occupant of the recently founded chair of pathology. His three major works are l'Anatomie descriptive (Descriptive Anatomy) (Cruveilhier, 1834a(Cruveilhier, , 1834b)), the outstanding Atlas d'Anatomie pathologique du corps humain (Atlas of Human Pathology) [START_REF] Cruveilhier | Anatomie pathologique Atlas[END_REF](Cruveilhier, , 1829) ) and the Traité d'anatomie pathologique (Treatise on Pathology) in five volumes (Cruveilhier, 1849). He was the first to describe cholesteatoma -also referred to as tumeur perlée de Cruveilhier (pearly tumor of Cruveilhier) -and was also one of the first to give an anatomical description of the multiple sclerosis pathology, later individualised on the clinical level by Vulpian and Charcot.

Jules Bernard Luys (1828Luys ( -1897) ) Médecin des hôpitaux de Paris, head of a department of medicine at La Salpêtrière hospital and then at the Charité Hospital in Paris, Luys (Figure 5) studied two very distinct areas. He made crucial discoveries in the field of neuroanatomy, giving the first description of the centro-median nucleus of the thalamus and of the subthalamic nucleus (Figure 6) (Luys, 1865). This nucleus was improperly coined by Luys bandelette acessoire des olives supérieures (accessory band of the superior olives) and later named Luys'schen corpus or corpus Luysii (Luys body) by August Henri Forel in 1877 [START_REF] Beck | The subthalamic nucleus; Part I: development, cytology, topography and connections[END_REF][START_REF] Parent | Jules Bernard Luys and the subthalamic nucleus[END_REF][START_REF] Pearce | The subthalamic nucleus and Jules Bernard Luys (1828-97)[END_REF]. He also published the very first photographic atlas of the encephalon and an outstanding atlas representing drawings of sections of the brain (Luys, 1873). At the end of his career Luys probably followed the trend of that time and decided to study the completely different field of mental pathology, and focused particularly on hysteria and hypnosis dedicating many works to these two conditions [START_REF] Parent | Jules Bernard Luys: a singular figure of 19th century neurology[END_REF]. He was a member of l'Académie de médecine (Academy of medicine), and one of the founders of the journal L'Encéphale.

Paul Broca (1824Broca ( -1880) ) Broca (Figure 7) was born in a Protestant family, in Sainte Foy-la-Grande, a small town in the Gironde département, near Bordeaux, where several illustrious men (including Gratiolet) were born [START_REF] Anonymous | Commémoration du centenaire de la mort de Paul Broca[END_REF][START_REF] Bendiner | Broca: adventurer in the recesses of the mind[END_REF]Breathnach, 1981b;[START_REF] Cambier | 100 ans après sa mort: 1880-1980[END_REF][START_REF] Castaigne | -1880[END_REF][START_REF] Finger | -1880[END_REF][START_REF] Frédy | -1880[END_REF][START_REF] Huard | -1880[END_REF]Jay, 2002;[START_REF] Monod-Broca | Le chirurgien, l'homme[END_REF], 2001[START_REF] Simpson | Phrenology and the neurosciences: contributions of F. J. Gall and J.G. Spurzheim[END_REF], 2006;[START_REF] Rössner | -1880[END_REF][START_REF] Valette | Allocution prononcée lors de la séance au centenaire de la mort de Paul Broca (1824-1880)[END_REF]. He was successively interne des hôpitaux de Paris (intern/resident of Paris hospitals), surgeon of the hospitals, professor at the faculty of medicine of Paris and member of the Académie de medicine. Broca is mostly renowned as a scientist in the fields of neurology (Broca, 1853(Broca, , 1866;;[START_REF] Houdart | Broca: précurseur des disciplines neurologiques[END_REF]D'Aubigné, 1980;[START_REF] Gusmao | Broca et les débuts de la neurochirurgie moderne[END_REF], anatomy (Bonamy et al., 1866;[START_REF] Delmas | Broca et l'anatomie[END_REF][START_REF] Huard | anatomiste[END_REF][START_REF] Denoix | Broca: l'anatomie pathologique, le cancer, la statistique[END_REF] and anthropology [START_REF] Androutsos | Paul Broca (1824-1880): founder of anthropology, pioneer of neurology and oncology[END_REF]Broca, 1862[START_REF] Broca | Mémoires d'anthropologie[END_REF]Broca, , 1873aBroca, , 1873bBroca, , 1873cBroca, , 1874Broca, , 1875Broca, , 1876Broca, , 1877aBroca, , 1879b;;[START_REF] Clower | Discovering trepanation: the contribution of Paul Broca[END_REF][START_REF] Pineau | Paul Broca et l'anthropologie[END_REF][START_REF] Schiller | Founder of French Anthropology, Explorer of the brain[END_REF]. He made major steps in the study of cerebral localizations (Broca, 1877(Broca, , 1879a;;[START_REF] Cowie | A place in history: Paul Broca and cerebral localization[END_REF][START_REF] Stone | Paul Broca and the first craniotomy based on cerebral localization[END_REF]. His name is associated to a speech disorder, Broca's aphasia, which he described thanks to the anatomoclinical observation of the foot lesions of the left ascending frontal convolution in his patient Leborgne [START_REF] Alajouanine | Paul Broca et l'aphasie[END_REF][START_REF] Broca | Écrits sur l'aphasie[END_REF]. This Bicêtre'patient called "Tan" within the hospital because this was all he could say, apart from monosyllabic words and a curse. In a paper published in 1861 in Bulletins de la Société Anatomique de Paris, Broca presented a detailed account of his post-mortem examination of Tan's brain [START_REF] Broca | Remarques sur le siège de la faculté du langage articulé, suivie d'une observation d'aphémie (perte de la parole)[END_REF]. In 1865, Broca proposed that the area for language was lateralized (Broca, 1865;[START_REF] Harris | Cerebral control for speech in right-handers and left-handers: an analysis of the views of Paul Broca, his contemporaries, and his successors[END_REF][START_REF] Harris | Broca on cerebral control for speech in right-handers and left-handers: a note on translation and some further comments[END_REF][START_REF] Huard | The brain of Paul Broca (1824-1880). Correlation of pathological and computed tomography findings[END_REF][START_REF] Lee | Paul Broca and the history of aphasia: Roland P. Mackay Award Essay[END_REF][START_REF] Schiller | Paul Broca and the history of aphasia[END_REF]. The "priority" of Broca's observation, its accuracy and the name that should be given to the syndrome were all disputed in public discussions and papers (Brown and Shobor, 1992;[START_REF] Lecours | Aphasie : querelles[END_REF]. In 1863 Gustave Dax (1815-1893) came forth with a report prepared by his deceased father, Marc Dax (1770-1837), one supposedly presented to the Montpellier Medical Society in 1836. There is no question that Dax's paper on the left hemisphere dominance for speech had been written in 1836, but there remains the nagging issue of whether it had been a public document [START_REF] Buckingham | The Marc Dax (1770-1837), Paul Broca (1824-1880) controversy over priority in science: left hemisphere specificity for seat of articulate language and for lesions that cause aphemia[END_REF][START_REF] Cubelli | A reappraisal of the controversy of Dax and Broca[END_REF].

At the end of his life, in 1878, Broca described in great detail a region that forms the inner border of the brain. He analyzed it in different mammals' brains and called it the limbic region (Broca's great limbic lobe). Broca did not found its real function, and considered it associated with the olfactory system; we know today that it is linked with emotions (Broca, 1878).

Broca was the father of anthropology, and founded the Société d'anthropologie de Paris (Paris anthropological Society), the Revue d'Anthropologie (Topinard and Broca, 1876) and l'Ecole d'Anthropologie (School of Anthropology) in 1859, 1872 and 1876, respectively. Broca was a great humanist, a freethinker (he took part in the foundation of the Société des Libres Penseurs (Society of Freethinkers). He was a republican hostile to the Empire, and became a senator. The surgeon Ulysse Trélat (1728-1890) ended his eulogy with the following words: "Great and powerful intelligence, bright and serene soul, noble heart, what a rare and worthy trinity, magnificent union of everything that makes the true grandeur of the human being […]" Louis Ranvier (1835Ranvier ( -1922) ) Born in Lyon, where he started his medical studies, Ranvier (Figure 8) was admitted as an interne des hôpitaux de Paris in 1860. He became a professor and was given a chair of general anatomy in 1875 at the Collège de France (the most prestigious scientific institution in France), where his teaching attracted considerable attention. Ranvier followed the experimental method taught by his master Claude Bernard (1813-1878), and always double-checked his morphological observations with the help of physiology [START_REF] Barbara | Louis Antoine Ranvier (1835-1922[END_REF]. His Manuel d'histologie pathologique (A Manual of Pathological Histology) in collaboration with Victor Cornil (1837-1908) is still considered as a masterpiece (Cornil and Ranvier, 1869). His numerous findings were related to bone and connective tissues, muscle histology (Ranvier and Renaut, 1880) and -above all -to nervous fibre histology (degeneration, regeneration and nerve endings) [START_REF] Barbara | Louis Ranvier (1835-1922): the contribution of microscopy to physiology and the renewal of French general anatomy[END_REF]Ranvier, 1889;Ranvier and Weber, 1878). He discovered the annular constrictions of the nervous fibers (narrowing or nodes) named after him, as well as the T-structure of the axons of spinal ganglia sensory neurons. In 1897 Ranvier founded Archives d'anatomie microscopique with Édouard-Gérard Balbiani (1823-1899), the very first journal of microscopic studies. He was a member of the Académie des Sciences and of the Académie de Médecine. His main colleagues were Charles Malassez (1842[START_REF] Tsuji | -1999) and the morphological identification of synapses[END_REF]), Louis-Félix Henneguy (1850-1928), Édouard-Gérard Balbiani and Justin-Marie Jolly who held a chair of histophysiology at the Collège de France in 1925.

André Victor Cornil (1837-1908) Cornil (Figure 9) had simultaneously a successful career in both medicine and politics (Anonymous, 1970). He was the oldest of Charcot's residents, a relentless worker, and was at the same time Médecin des Hôpitaux de Paris and professor of pathology. In 1882 he replaced Charcot who had taken over the chair dedicated to the study of the nervous system. Cornil was a clinician but also -and mainly-a pathologist. He was passionate about post mortem examinations and histopathology (Cornil, 1863(Cornil, , 1864(Cornil, , 1865(Cornil, , 1879(Cornil, , 1885)). He wrote many papers and his Manuel d'histologie pathologique (A Manual of Pathological Histology) which he wrote in collaboration with Louis Ranvier, is a remarkably clear condensation of all his observations (Cornil and Ranvier, 1869). His collaboration with Ranvier began with the small private histological laboratory they founded on Rue Christine, and went on at the Collège de France and at the chair of Pathological anatomy. On the political level, Victor Cornil was a Congressional representative of the Allier French département (County), senator-mayor of his small village Creuzier-le-neuf, regional councillor, prefect from the 6th to the 24th of September 1870, and vice-president then president of the Regional Council of Allier. He was an anti-monarchist and presided over the Republican League in the 6th arrondissement of Paris during the Commune.

Albert Gombault (1844Gombault ( -1904) ) Gombault (Figure 10) was resident of Charcot in 1872 and defended his MD thesis on amyotrophic lateral sclerosis in 1877 (Gombault, 1877). He was appointed Médecin des Hôpitaux de Paris in 1882 and head of a department of medicine at the Hôpital des Incurables d'Ivry (current Charles Foix -Jean Rostand hospital). He was a founding member of the Société de Neurologie de Paris in 1899, chef des travaux anatomiques (chief of anatomical works) at the faculty of medicine and curator of the Musée Dupuytren. His neurological, neuropathological and neurohistological works are still of importance today [START_REF] Clarac | Albert Gombault (1844-1904). Un pionnier des neurosciences[END_REF][START_REF] Gombault | Contribution à l'étude des lésions systématisées dans les faisceaux blancs de la moelle épinière[END_REF]. With official authorization from the Faculty of Medicine, he founded an open course on histology in 1887. He studied saturnism in guinea pigs that had been fed during six months with food containing lead. If there were no clear behavioural disturbances, most nervous fibers showed marked defects of myelin. Using the teasing method, he dissociated the nervous trunks of the brachial plexus and of the sciatic nerve. The axons always stayed intact but the Schwann cell sheaths were severely affected. These lesions might heal to some extent if lead ingestion was discontinued. Subsequently he demonstrated similar lesions in humans with lead poisoning. His pictures were reproduced in Greenfields Neuropathology, up to the 1976 edition. Gombault wrote the fifth part of the Traité d'histologie pathologique (Treatise on Pathological Histology, by Cornil and Ranvier), in collaboration with his beloved student Claude Philippe . He published several papers, but his name is more particularly associated with the névrite peri-axile (periaxial neuritis) of Gombault and Philippe (Gombault, 1880a(Gombault, , 1880b)).

Jean Nageotte (1866Nageotte ( -1948) ) As a resident in 1889, Nageotte (Figure 11) defended his thesis on tabes dorsalis while working at the laboratory of Fulgence Raymond , at Lariboisière hospital [START_REF] Nageotte | Tabes et paralysie générale[END_REF]. He was named médecin aliéniste des hôpitaux de Paris (psychiatrist of Paris hospitals) at Bicêtre hospital, then at the Salpêtrière hospital, and was head of Joseph Félix Babinski's (1857Babinski's ( -1932) ) department for pathological and histological exams, where he designed a new brain microtome for the laboratory. He did several important reports on the human brain [START_REF] Nageotte | Notice sur les travaux scientifiques[END_REF][START_REF] Nageotte | La carte de l écorce cérébrale[END_REF]. In collaboration with Babinski, he described the Babinski-Nageotte syndrome of vascular lesion of the medulla in 1902 and published works on cerebrospinal fluid cytology [START_REF] Babinski | Hemiasynergie latéro-pulsion et myosis bulbaires avec hémianesthésie et hémiplégie croisées[END_REF]. He succeeded to Louis Ranvier and took over the chair of comparative histology (which had originally been created for Ranvier), when the latter left in 1937. Despite his achievements, Nageotte was never elected to the Académie des Sciences. In 1911 he paid a tribute to his teachers in the summary of his works, and especially to Albert Gombault of whom he had been a resident, to Louis-Charles Malassez (1842[START_REF] Tsuji | -1999) and the morphological identification of synapses[END_REF], who accepted him in his laboratory and to Babinski. Nageotte did considerable research on the microscopic anatomy of the connective tissue [START_REF] Nageotte | L'organisation de la matière dans ses rapports avec la vie: études d'anatomie générale et de morphologie expérimentale sur le tissu conjonctif et le nerf[END_REF][START_REF] Nageotte | Structures à surfaces hydrophobes, structures vacuolaires[END_REF][START_REF] Nageotte | Sur l'emploi des greffes de tissu conjonctif mort dans la chirurgie réparatrice (Tendon et Nerf)[END_REF] and of the nervous system and published a very detailed book entitled La structure fine du Système Nerveux (Fine Structure of the Nervous System) in 1905 [START_REF] Nageotte | La structure fine du système nerveux[END_REF]. He then dedicated his research to myelin and physicochemical properties and published a book in 1937 entitled Morphologie des gels lipoïdes, myéline, cristaux liquides, vacuoles (Morphology of Lipoid Gels, Myelin, Liquid crystals and Vacuoles) [START_REF] Nageotte | Morphologie des gels lipoïdes. Myéline. Cristaux liquides. Vacuoles[END_REF]. He was the teacher of René Couteaux. Following an accident Nageotte was struck down by hemiplegia and became progressively deaf.

René [START_REF] Tsuji | -1999) and the morphological identification of synapses[END_REF]Couteaux ( -1999) ) Couteaux (Figure 12) was docteur en Médecine (MD), professor of histology and cytology at the Paris Faculty of Sciences and a pioneer in the anatomical and ultrastructural knowledge of synapses [START_REF] Couteaux | Recherches sur l'histogénèse du muscle strié des mammifères et la formation des plaques motrices[END_REF]. He began his studies on the neuromuscular junction in 1935. On the biochemical level, he co-established with David Nachmanson the concentration of the acetyl-cholinesterase activity in the neural area of muscle fibers even after denervation. Thanks to Janus green B staining, Couteaux defined the postsynaptic membrane, the subneural organization and the motor end plate and published his results in his PhD thesis in 1947 [START_REF] Couteaux | Contribution à l'étude de la synapse myoneurale[END_REF]. After hearing a speech from Sanford Palay at Caracas congress in 1957, from 1960 onwards, Couteaux decided to study the presynaptic portion of the synapse (Couteaux and Pécot-Dechavassine, 1970b). In 1970, he managed to obtain characteristic images of the exocytosis by opening synaptic vesicles (Figure 13) (Couteaux and Picot-Dechavassine, 1970a;[START_REF] Tsuji | -1999) and the morphological identification of synapses[END_REF]. Luys was the first to describe this brain region which he improperly denominated 'accessory band of the superior olives'. This anatomical structure is not clearly labeled on this drawing, but can be recognized as the one prolonging (as the outer and upper part) the 'susbtantia nigra' which is labeled N°12. Reproduction de l'un des dessins (Planche XXVI) qui peut être trouvé dans le traité d'anatomie du cerceau humain de 1865 de Luys, situé au niveau du noyau sous-thalamique (voir la flèche large). Luys fut le premier à décrire cette région du cerveau qu'il appela de façon impropre « bandelette accessoire des olives supérieures ». Cette structure anatomique n'est pas indiquée de façon claire dans la légende de ce dessin, mais elle peut être identifiée comme la région prolongeant en haut et en dehors la « substance noire » (« locus niger ») étiquetée N°12 (©BIU Santé).

FiguresFigures

  Figures and institutions of the neurological sciences in Paris from 1800 to 1950. Introduction and Part I: Neuroanatomy François Clarac, Jean-Gaël Barbara, Emmanuel Broussolle, Jacques Poirier

FiguresFigure

  Figures

  Figure 1. Picture of Vicq D'azyr. Portrait de Vicq D'Azyr (Académie Nationale de Médecine).

Figure 2 .

 2 Figure 2. Picture of Bichat. Portrait de Bichat (©BIU Santé).

Figure 3 .

 3 Figure 3. Picture of Gall. Portrait de Gall (©BIU Santé).

Figure 4 .

 4 Figure 4. Picture of Cruveilhier. Portrait de Cruveilhier (Académie Nationale de Médecine).

Figure 5 .Figure 6 .

 56 Figure 5. Picture of Luys. Portrait de Luys (Académie Nationale de Médecine). .

Figure 7 .

 7 Figure 7. Picture of Broca. Photographie de Broca (Académie Nationale de Médecine).

Figure 8 .

 8 Figure 8. Picture of Ranvier. Portrait de Ranvier (©BIU Santé).

Figure 9 .

 9 Figure 9. Picture of Cornil. Photographie de Cornil (©BIU Santé).

Figure 10 .

 10 Figure 10. Picture of Gombault. Portrait de Gombault (©BIU Santé).

Figure 11 .

 11 Figure 11. Picture of Nageotte. Photographie de Nageotte.

Figure 12 .

 12 Figure 12. Picture of Couteaux (personal collection). Photographie de Couteaux (collection personnelle de Jacques Poirier).

Figure 13 .

 13 Figure 13. Exocytotic opening of the synaptic vesicles into the synaptic cleft at the level of the active zone (arrow) of the frog neuromuscular junction (magnification, ×205000). Ouverture par exocytose des vésicules synaptiques dans la fente synaptique au niveau de la zone active (flèche) de la junction neuromusculaire de la grenouille (agrandissement X 205000) Reproduced with kind permission of Académie des Sciences. From R. Couteaux and M. Pécot-Dechavassine (1970) Comptes Rendus Hebdomadaires des Séances de l'Académie des Sciences, Série D: Sciences Naturelles, 271, 2346-2349. (Académie des Sciences -Institut de France)

Acknowledgements

The authors would like to thank Chloé Loiraud, Yann Bregeras, Sandrine Jamen and Jessica Moreau from Bibliothèque Médicale, Hôpital Neurologique Pierre Wertheimer, Lyon, France for their tremendous help, Chantal Barbara, Marjorie Lorch (ISHN), the École des Neurosciences de Paris, the Club d'Histoire des Neurosciences from the Société des Neurosciences and the BIU Santé (Bibliothèque Inter Universitaire de Santé de Paris) and the Académie Nationale de Médecine and Académie des Sciences for the reproduction of photographs.

 -------------------------------------


Jean-Gaël Barbara

Emmanuel Broussolle
email: emmanuel.broussolle@chu-lyon.fr

Jacques Poirier

François Clarac

François Magendie

Marie Jean

Pierre Flourens

Claude Bernard

Charles Edouard Brown-Séquard

Etienne Jules Marey

Alfred Fessard

Denise Albe-Fessard

biographies résumées de

Keywords: histoire, Paris, neurosciences, anatomie, physiologie, neurologie, psychiatrie, psychologie anatomie, physiologie, neurologie, et psychiatrie-psychologie

We present a short historical review of the major figures and institutions that contributed to make Paris a renowned centre of physiology and neurology during the XIX th and the first half of the XX th century. We purposely chose to focus on the period 1800-1950, as 1800 corresponds to the actual beginning of experimental physiology of the nervous systemwhat is here referred to as "neuroscience"and 1950 marks its exponential rise. Our presentation is divided into four chapters, matching the main disciplines which have progressed and contributed the most to the knowledge we have of the brain sciences: anatomy, physiology, neurology, and psychiatrypsychology.

Introduction

The present articlewhich deals with neurophysiology -is the second of four parts of a short historical review of the major institutions and figures who contributed to make Paris a renowned centre of physiology and neurology during the XIX th and the first half of the XX th century.

The experimental physiological studies of the nervous system in France developed in the XIX th in France with François Magendie (1783Magendie ( -1855)). His contribution and also controversies with the great British neurophysiologist Charles Bell (1774-1842) have already been described at length. The Collège de France in Paris was one of the most renowned places for physiological studies during all this period. In his famous 1865 Introduction à l'étude de la médecine expérimentale (Introduction to the Study of Experimental Medicine), Claude Bernard (1813Bernard ( -1878) ) insisted on the major importance of experiments in medical sciences: "La méthode expérimentale, considérée en elle-même, n'est rien autre chose qu'un raisonnement à l'aide duquel nous soumettons méthodiquement nos idées à l'expérience des faits… L'expérimentation ou l'art d'obtenir des expériences rigoureuses et bien déterminées est la base pratique et en quelque sorte la partie exécutive de la méthode expérimentale appliquée à la médecine" («Considered in itself, experimental method is nothing but a reasoning which helps us methodically to submit our ideas to the experience of facts… The experimentation, or art of obtaining rigorous and well-determined experiments is the practical basis and to some extent the executive part of the experimental method applied to medicine").

Neurophysiology had close links with chemistry and physics. This is the case of Etienne-Jules [START_REF] Lüderitz | -1904[END_REF]Marey ( -1904)), a remarkable man whose main goal, as a physician, was to record biological phenomena in the best possible manner. He invented all kinds of devices which allowed him to apprehend either slow or extremely fast phenomena. Marey did not develop most of his experiments and left this task to others.

Much later, Alfred Fessard (1900Fessard ( -1982) ) created the first major laboratoire de physiologie nerveuse du CRNS (National Center for Scientific Research laboratory of nervous physiology) in the 1950s, on the premises Marey had obtained nearly 50 years before, for his photographic studies.

Apart from Paris, several leading countries in Europe and North America took major steps in neurophysiology during the XIX th and the first half of the XX th century. Although the present paper is not focused on this topic, we will briefly mention some of the most important contributors. In Germany, Ernst Heinrich Weber (1795-1878) and Gustav Fechner (1801-1887) founded the psychophysical method. Wilhelm Wundt (1832Wundt ( -1920) ) became one of the pioneers in experimental psychophysiology. Johannes Peter Müller (1801-1858) did his famous experiments on sensory and perceptive senses. Several of his pupils did their own renowned research, notably Hermann von Helmholtz (1821-1894), Emil du Bois-Reymond (1818-1896), Theodor Schwann (1810[START_REF] Marey | Le fusil photographique[END_REF]), Friedrich Gustav Jakob Henle (1809-1885), Carl Ludwig (1816-1895) and Ernst Haeckel (1834-1919). In Russia, Ivan Petrovich Pavlov (1849-1936) was professor of physiology in Saint-Petersburg. He invented the conditioned reflex for which he received the Nobel Prize in 1904. In the United Kingdom, Charles Sherrington (1857[START_REF] Olmsted | Bichat vu par Magendie[END_REF]) and Edgar Adrian (1889[START_REF] Albury | Experiment and explanation in the physiology of Bichat and Magendie[END_REF] made major findings on the functions of neurons for which they received the Nobel Prize in 1932. Henry Dale (1875-1968) and Otto Loewi (1873-1961), formerly German, and then American citizens, received the Nobel Prize in 1936 for their discovery of the chemical function of acetylcholine in neurotransmission. In the USA, Walter Bradford Cannon (1871-1945) expended the experimental theories of Claude Bernard. In 1944Joseph Erlanger (1874-1965) and Herbert Spencer Gasser (1888[START_REF] Albe-Fessard | Activités électriques caractéristiques de quelques structures cérébrales chez l'homme[END_REF] won the Nobel Prize for their work on the peripheral nerve fibers.

We present below the biographical sketches of some of the most important historical figures among Parisian neurophysiologists.

François MAGENDIE (1783MAGENDIE ( -1855) ) Magendie (Figure 1) was born in Bordeaux and studied medicine in Paris [START_REF] Albury | Experiment and explanation in the physiology of Bichat and Magendie[END_REF][START_REF] Bloch | Claude Bernard, and the interrelation of science, history, and philosophy[END_REF][START_REF] Breathnach | Biographical sketches No. 34-Magendie[END_REF][START_REF] Clarac | Chapter 40. History of Neurology in France[END_REF]Fenton, 1951;[START_REF] Haas | François Magendie (1783-1855)[END_REF][START_REF] Lazorthes | François Magendie (1783-1855)[END_REF][START_REF] Olmsted | Bichat vu par Magendie[END_REF][START_REF] Schiller | Magendie on medicine[END_REF][START_REF] Shampo | François Magendie: early French physiologist[END_REF]Stahnish, 2009;[START_REF] Tubbs | François Magendie (1783-1855) and his contributions to the foundations of neuroscience and neurosurgery[END_REF]. He was appointed resident and defended his thesis in 1808 (Magendie, 1808). As an assistant in anatomy of Guillaume Dupuytren (1777-1835), he was involved in research on the spinal cord and spinal nerves. During the following decades, Magendie invested his time to the study of physiology [START_REF] Gallistel | Magendie, and the proposals to restrict the use of animals in neurobehavioral research[END_REF][START_REF] Gans | An early example of the use of surgical techniques in solving a physiologic problem (François Magendie)[END_REF][START_REF] Magendie | Précis élémentaire de physiologie[END_REF]Magendie, , 1817Magendie, , 1834[START_REF] Magendie | Leçons sur les fonctions et les maladies du système nerveux[END_REF][START_REF] Saavedra-Delgado | François Magendie on anaphylaxis (1839)[END_REF]. He favoured the new trend in France of using instruments such as the sphygmomanometer, the thermometer or the aerometer. In 1809, he analyzed the poison contained in the strychnos (a tropical shrub) [START_REF] Magendie | Examen de l'action de quelques végétaux sur la moelle épinière[END_REF], which enabled him to isolate strychnine in 1818. He introduced it as a medicinal drug, as well as emetine, morphine, iodides and bromides. His research was continued and corroborated shortly after by Henri Milne-Edwards (1800-1885). In 1821, he founded the first journal dedicated to physiology, the Journal de Physiologie expérimentale. Magendie is best known for the laws named after him and for his argument with Charles Bell (1774-1842), the famous British neurophysiologist [START_REF] Jørgensen | Aspects of the history of the nerves: Bell's theory, the Bell-Magendie law and controversy, and two forgotten works by P[END_REF]. In 1822 he dissected a litter of puppies and dissociated -in the spinal roots -the efferent motor conduction in the ventral root from the sensory afferent conduction in the dorsal root.

He was nominated médecin des hôpitaux de Paris in 1818 and headed a department of medicine at the Hôtel-Dieu hospital in 1830. In 1831, he became Professor at the Collège de France, where he met Claude Bernard his assistant. Magendie explored the functions of the cerebellum and of the 4 th ventricle and studied the pressure applied by the cerebrospinal fluid with a sphygmomètre (sphygmomanometer) designed by Jean-Louis Poiseuille (1799-1869) (Magendie, 1842;[START_REF] Sourkes | Magendie and the chemists: the earliest chemical analyses of the cerebrospinal fluid[END_REF]Stahnish, 2008).

From a philosophical point of view, Magendie was a materialist and conceived of the human intellect in a scientific manner escaping the comfortable religious belief of the divine nature and immortality of the soul. He thought scientists should study human intellect as if it resulted from a single organ, the brain, according to the general laws of physiology (Magendie, 1817).

Marie Jean Pierre FLOURENS (1794-1867) Flourens (Figure 2) was born at Maureilhan in Hérault département (County) in the south of France and studied medicine in Montpellier, where he graduated in 1813 [START_REF] Yildirim | Marie Jean Pierre Flourens (1794 1867): an extraordinary scientist of his time[END_REF]. He was the assistant of Georges Cuvier (1769-1832), became a member of the Académie des Sciences in 1828 and then a professor of comparative anatomy at the Collège de France in Paris. He was elected at the Académie Française in 1840 in a contest with Victor Hugo. Flourens was an accomplished experimenter and developed the techniques of ablation and of selective stimulation of the brain, which enabled the study of walking, swimming and flying of numerous animal species, notably in birds, following and translating the work of Italian anatomist Luigi Rolando (1773 -1831) [START_REF] Clarac | Some historical reflections on the neural control of locomotion[END_REF][START_REF] Flourens | Recherches physiques sur les propriétés et les fonctions du système nerveux dans les animaux vertébrés[END_REF]Flourens, , 1825Flourens, , 1844)). He described his results in his famous 1824 book (Figure 3) entitled: Recherches expérimentales sur les propriétés et les fonctions du système nerveux chez les animaux vertébrés (Experimental Studies of the Properties and Functions of the Vertebrate Nervous System) (Flourens and Rolando, 1824). Flourens was asked by Napoléon Bonaparte to assess the doctrine of Gall which he initially followed and soon rejected. Many of his studies were made in this context, fighting the doctrine of localisation in the cortex. Flourens clearly showed the role of the cerebellum in motor coordination [START_REF] Boling | Historical contributions to the modern understanding of function in the central area[END_REF][START_REF] Fine | The history of the development of the cerebellar examination[END_REF][START_REF] Manto | The cerebellum, cerebellar disorders, and cerebellar research-two centuries of discoveries[END_REF][START_REF] Pearce | Marie-Jean-Pierre Flourens (1794-1867) and cortical localization[END_REF][START_REF] Tizard | Theories of brain localization from Flourens to Lashley[END_REF], and the function of the ear labyrinth in equilibrium using ablation studies. He adopted the 1812 experiments of César Julien Legallois (1770-1814) and localized with more accuracy the respiratory centre that he located at the apex of the calamus on the floor of the fourth ventricle within the medulla oblongata [START_REF] Pearce | Marie-Jean-Pierre Flourens (1794-1867) and cortical localization[END_REF][START_REF] Tizard | Theories of brain localization from Flourens to Lashley[END_REF]. He defined le noeud vital (vital node) situated at the apex of the calamus scriptorius and no larger than a pin head. He was one of the fiercest opponents to Franz Joseph Gall (1758-1828) and phrenology (Flourens, 1842(Flourens, , 1863;;[START_REF] Flourens | Phrenology examined[END_REF]. His ideas on the unity of the brain suggested its plasticity. In 1847, he described the effects of chloroform and ether on the nervous system at the Académie des sciences. He is also known as the master of the physiologist, anatomist and neurologist, Alfred Vulpian (1826-1887).

Claude BERNARD (1813BERNARD ( -1878) ) Claude Bernard (Figure 4) was born in Saint-Julien in the Beaujolais area near Lyon. After an aborted career as a writer, he started medical studies and was appointed interne des hôpitaux de Paris. He became a docteur en médecine (MD) in 1843 and worked under the direction of Magendie at the Collège de France. He defined the role of the pancreas in digestion in 1846, by showing that it secretes a substance allowing the digestion of fats (Bernard, 1846). He later carried out the expérience du foie lavé ("washed liver experiment") which described the transformation, storage and use of sugar within the body (Bernard, 1853;[START_REF] Kahn | Entre dogmatisme et empirisme: la découverte de la fonction glucoformatrice et glucosecretrice du foie par Claude Bernard[END_REF][START_REF] Rodriguez De Romo | Claude Bernard and pancreatic function revisited after 150 years[END_REF][START_REF] Swan | The liver forms, stores and secretes glucose (Claude Bernard, 1860)[END_REF]. He also examined the functions of the autonomous nervous system [START_REF] Reader | The role of Claude Bernard and others in the discovery of Horner's Syndrome[END_REF] and discovered, in opposition to Charles Brown-Séquard (1817-1894), the function of the vasomotor nerves, responsible for blood flow regulation by contraction or dilatation of the blood vessels. In order to provide an explanation to the chemical balance that exists in every organism, he was the first one to suggest the concept of milieu intérieur ("internal medium", that is to say the internal environment) [START_REF] Wasserstein | Death and the internal milieu: Claude Bernard and the origins of experimental medicine[END_REF], better known as homeostasis and defined by Walter Bradford Cannon in the 1930s [START_REF] Cooper | Emergence of the concept of homeostasis[END_REF][START_REF] Jeanrenaud | De Claude Bernard a la boucle régulatrice reliant l'hypothalamus à la péripherie: implications dans l'homeostasie du poids corporel et dans l'obésité[END_REF].

Claude Bernard took over the chair of experimental physiology created for him at the Sorbonne University in 1854 (Bernard andTripier, 1858a, 1858b). He succeeded Magendie at the Collège de France after the latter's death in 1855, and became a professor at the Muséum (National Museum of Natural History) in 1868. He laid the foundations of experimental medicine in L'Introduction à l'étude de la médecine expérimentale (An Introduction to the Study of Experimental Medicine), published in 1865 (Bernard, 1858(Bernard, , 1865a(Bernard, , 1865b;;[START_REF] Noble | the first systems biologist, and the future of physiology[END_REF][START_REF] Normandin | Claude Bernard and an introduction to the study of experimental medicine: "physical vitalism," dialectic, and epistemology[END_REF][START_REF] Tan | Claude Bernard (1813-1878): father of experimental medicine[END_REF]. He then became a member of Académie Française and a person of international reputation. He died in 1878 and had a state funeral, thus becoming the very first Frenchman of science to receive such an honour. Claude Bernard was a great physiologist and professor who attracted young students from all over the world including Russian anatomists and physiologists. He is mentioned in the novel by Dostoyevsky, The brothers Karamazov. He was highly praised and respected worldwide as a pioneer of experimental physiology and founder of the first great physiology school in France. However, historical analyses of his students and of early XXth century science reveal the limits of his epistemology and that of his faith in physiological determinism, his rejection of Darwin's theory and his rejection of statistics in biological sciences.

Charles Édouard BROWN-SÉQUARD (1817-1894)

Born in Mauritius, to an Irish-American officer from Philadelphia and a French mother from Marseille, Brown-Séquard (Figure 5) spent his life between France, England, Mauritius and the USA [START_REF] Bonduelle | Histoire de la Neurologie -Charles-Édouard Brown-Séquard[END_REF][START_REF] Dubb | C E Brown-Séquard (1817-1894) -multi-national neurologist[END_REF][START_REF] Haas | Charles Édouard Brown-Séquard (1818-94)[END_REF][START_REF] Jay | A portrait in history: The extraordinary international career of Dr Brown-Séquard[END_REF][START_REF] Koehler | Charles-Édouard Brown-Séquard (1817-1894)[END_REF][START_REF] Laporte | Charles-Édouard Brown-Séquard: an eventful life and a significant contribution to the study of the nervous system[END_REF][START_REF] Rengachary | Charles-Édouard Brown-Séquard: an eccentric genius[END_REF][START_REF] Simonetti | Charles Édouard Brown-Séquard[END_REF]. He was a student of Armand Trousseau (1801-1867) and worked at the Charité hospital where he became the protégé of Pierre-François-Olive Rayer (1793-1867). He described what is known as the Brown-Séquard syndrome (Brown-Séquard, 1861; [START_REF] Tattersall | Brown-Séquard and his syndrome[END_REF], a lateral hemisection of the spinal cord [START_REF] Aminoff | Historical perspective. Brown-Séquard and his work on the spinal cord[END_REF]Brown-Séquard, 1855a, 1855b), in his 1846 medical thesis in Paris (Brown Séquard, 1846) His second major contribution is related to the sympathetic nervous system (Brown-Séquard, 1954). In 1852, in collaboration with Claude Bernard he demonstrated the constriction of blood vessels of the ear after stimulation of the cervical nerve [START_REF] Laporte | Brown-Séquard and the discovery of the vasoconstrictor nerves[END_REF].

With the support of Paul Broca (1824-1880), Brown-Séquard gained a position in Philadelphia but left for Mauritius to cure a cholera epidemic in 1854. He then moved from Mauritius to Boston in 1856 and decided to live at London's Royal College, where he inspired the young John Hughlings Jackson . Brown-Séquard took part in the founding of the London school of neurology at Queen Square. He succeeded Claude Bernard in Paris at the Collège de France after the latters's death in 1878 and was helped in his work by his student Arsène d 'Arsonval (1851'Arsonval ( -1940)).

Brown-Séquard did several major studies on the physiology and pathophysiology of the nervous system (Brown-Séquard, 1853, 1856b, 1865, 1868, 1871). With Jean-Martin Charcot (1825-1893) and Alfred Vulpian (1826-1887), Brown-Séquard founded the Archives de physiologie normale et pathologique, a scientific journal succeeding the Journal de la physiologie de l'homme et des animaux (Journal of Human and Animals Physiology) (1858-1863), edited under his direction. As an opponent of the cerebral localizations he debated with Charcot at the Société de Biologie (1875-1876) [START_REF] Goetz | Battle of the titans: Charcot and Brown-Séquard on cerebral localization[END_REF]. One of the other major contributions of Brown-Séquard was to show the importance of internal secretions and the role of adrenal glands. In 1856 he discovered adrenalin/epinephrine and published Recherches expérimentales sur la physiologie et la pathologie des capsules surrénales (Experimental Researches on the Physiology and the Pathology of Adrenal Capsules) (Brown-Séquard, 1856a). In 1889, he went as far as presenting a report claiming he had rejuvenated himself thanks to subcutaneous injections of animal testicular extracts. However extravagant this publication may seem, it undoubtedly stimulated the research on sex hormones [START_REF] Rengachary | Charles-Édouard Brown-Séquard: an eccentric genius[END_REF]. [START_REF] Lüderitz | -1904[END_REF]-1904) Marey (Figure 6) was born in Beaune in Burgundy and studied medicine in Paris (Baron, 1983;[START_REF] Campan | Marey et la capture des temps physiologiques[END_REF][START_REF] Debru | l'innovation médicale[END_REF][START_REF] Lefebvre | La longue marche d' Étienne-Jules Marey[END_REF][START_REF] Lüderitz | -1904[END_REF][START_REF] Mcintyre | Medical statues. Étienne Jules Marey (1830-1904[END_REF]Merlen, 1985). He was appointed interne des hôpitaux de Paris in 1854 and defended his medical thesis Recherches sur la circulation du sang à l'état physiologique et dans les maladies (Research on Blood Circulation in Normal and Pathological States) in 1859 (Marey, 1859). He was a physician but he did not practice much and turned to research (Marey, 1875). For the measure of different sort of physiological phenomena, Marey invented a great number of apparatus that have been used in France in the majority of physiological laboratories and by generations of students. He measured the electrical activity of the heart using a mercury Lippmann electrometer. One of his most important inventions was the sphygmograph: a device recording pulse waves measured by arterial catheterism in horses [START_REF] Lawrence | Physiological apparatus in the Wellcome Museum. 1. The Marey sphygmograph[END_REF]Marey, 1860). This was presented to the Académie des Sciences in 1860. Marey published Du Mouvement dans les fonctions de la vie (On Movement in Life's Functions) in 1868 (Marey, 1868). He was appointed professor of physiology at the Collège de France in 1869 and dedicated his life to any possible movement. As many of these phenomena are invisible to the naked eye, he invented two techniques that foreshadowed the cinematograph [START_REF] Michaelis | Marey -physiologist and first cinematographer[END_REF][START_REF] Silverman | Étienne-Jules Marey: 19th century cardiovascular physiologist and inventor of cinematography[END_REF] and greatly influenced the academic art of the XIX th century and the beginnings of modern art: the graphic method (Figure 7) and the chronophotography [START_REF] Laporte | fondateur de la méthode graphique[END_REF][START_REF] Mannoni | de la méthode graphique au cinematographe[END_REF]. He published in 1873 La Machine animale. Locomotion terrestre et aérienne (Animal Mechanism: a Treatise on Terrestrial and Aerial Locomotion) [START_REF] Marey | La machine animale: locomotion terrestre et aérienne[END_REF][START_REF] Marey | Études photographiques sur la locomotion de l'homme et des animaux[END_REF]. In 1874, the astronomist Jules Janssen designed the photographic revolver, intended to capture the movement of celestial bodies. Marey developed the chronophotographic gun in 1882 [START_REF] Marey | Le fusil photographique[END_REF]. Thanks to this famous invention he could photograph a bird's flight on 12 consecutive frames by the graphic method and chronophotography. In 1882, Marey created the Station Physiologique du Bois de Boulogne (Physiological Laboratory of Bois de Boulogne in Paris), funded by the French government, to which the Marey Institute was later added. This institute was the basis for the new research laboratory of electrophysiology created by Alfred Fessard before the Second World War (Barbara, 2010).

Alfred FESSARD (1900FESSARD ( -1980) ) Alfred Fessard (Figure 8) was both a physicist and a physiologist (Buser, 1982;[START_REF] Buser | Tribute: Alfred Fessard[END_REF]. He was influenced by the psychologist Henri Piéron (1881Piéron ( -1964) ) and was a préparateur (assistant) in his psychophysiology laboratory of l'Ecole Pratique des Hautes Etudes (Practical School of Higher Studies), an institution of higher learning created in 1868, which offered post-graduates studies in a variety of highly specialized fields in Paris. He worked with Daniel Auger at the Tamaris-sur-Mer marine biological laboratory near Toulon on the Mediterranean Sea coast. They carried out various electrophysiological recordings on preparations of invertebrates. There Fessard met Angélique Arvanitaki (1901[START_REF] Breathnach | Biographical sketches No. 34-Magendie[END_REF] and discovered the giant neurons of the mollusc Aplysia. They studied the electrical activities of crustacean nerves. It was the subject of Angelique Arvanitaki thesis. Alfred Fessard's works of 1935, on the EEG, in collaboration with Gustave Durup showed the conditioning of the blocking of the alpha rhythm [START_REF] Durup | L'électroencéphalogramme de l'homme. Observations psychophysiologiques relatives à l'action des stimuli visuels et auditifs[END_REF]. Fessard was influenced by the renowned British neurophysiology school and revived neurophysiology in France and tried to develop researches on both cellular and integrated levels (Fessard, 1936a(Fessard, , 1936b[START_REF] Fessard | Organes des sens[END_REF]. He was appointed professor at the Collège de France and director of the Marey Institute. [START_REF] Fessard | Organes des sens[END_REF], he invited Siegmund Feldberg (1900[START_REF] Griffin | Famous names in toxicology. Claude Bernard 1813-1878[END_REF]) and David Nachmansohn (1899[START_REF] Breathnach | Biographical sketches No. 34-Magendie[END_REF], two Jewish researchers escaping the Nazi government in Germany, to the marine biological laboratory of Arcachon (located on the Atlantic Ocean shore near Bordeaux). Together, they showed the cholinergic nature of the transmission in the electrical lobe of torpedo, an argument in favour of the chemical theory [START_REF] Feldberg | The cholinergic nature of the nerves to the electric organ of the Torpedo (Torpedo marmorata)[END_REF]. Since then, the international reputation of Fessard has never been contested. Fessard became a member of the Académie Nationale de Médecine and of the Académie des Sciences and after World War II, assembled all the scientific and institutional conditions required to create a French school of neurophysiology of high international standard [START_REF] Fessard | Les mécanismes élémentaires de la transmission synaptique[END_REF][START_REF] Lapicque | Colloques internationaux du Centre national de la recherche scientifique[END_REF]. He wrote an article on the neuronal networks and consciousness entitled Mechanisms of Nervous Integration and Conscious Experience at the international congress of Laurentides in 1953 [START_REF] Fessard | Mechanisms of nervous integration and conscious experience[END_REF]. He made his laboratory one of the most important scientific places in Europe, owing to the presence of renowned students and researchers such as his wife Denise Albe-Fessard, Pierre Buser, Jacques Paillard (1920[START_REF] Laporte | Charles-Édouard Brown-Séquard: an eventful life and a significant contribution to the study of the nervous system[END_REF]), Ladislav Tauc (1926[START_REF] Jay | A portrait in history: The extraordinary international career of Dr Brown-Séquard[END_REF] and others (Albe- [START_REF] Albe-Fessard | Recent advances on the neurophysiological bases of pain sensation[END_REF][START_REF] Bullock | Electroreceptors and other specialized receptors in lower vertrebrates[END_REF][START_REF] Fessard | Sur la complexité hiérarchisée du système nerveux et ses modèles d'organisation[END_REF][START_REF] Fessard | Colloque de neurophysiologie humaine appliquée à la psychologie et à la psychiatrie. Activités évoquées et leur conditionnement chez l'homme normal et en pathologie mentale[END_REF]Fessard et al., 1973;[START_REF] Morin | Introduction[END_REF]. In the 1960s, Fessard took part in the foundation of the International Brain Research Organization (IBRO), and he became a member of its executive committee and of the governing council.

Denise ALBE-FESSARD (1916[START_REF] Jørgensen | Aspects of the history of the nerves: Bell's theory, the Bell-Magendie law and controversy, and two forgotten works by P[END_REF] Denise Albe-Fessard (Figure 8), an emblematic figure of French neuroscience, obtained her diploma from l'École de physique et chimie de la Ville de Paris (Paris School of Physics and Chemistry) and was associated with the works carried out at Marey Institute from the beginning. In 1942, she married Alfred Fessard, who headed the CNRS Center of nervous physiology and electrophysiology. She defended her thesis on the electrogenesis of the electrical discharge in electric fishes, gymnotus, torpedo and ray in 1950 (Albe [START_REF] Albe-Fessard | Recherches électrophysiologiques sur la décharge du gymnote, de la torpille[END_REF]. In the 1945-1950s, Denise Albe-Fessard and her husband carried on their researches on these particular electric fish at the marine biological laboratory of Arcachon (near Bordeaux), and in Rio de Janeiro with Carlos Chagas . Albe-Fessard was one of the first to succeed in recording intracellularly neurons of the cat cortex, after having refined her method on the nuclei of Torpedo (Albe- Fessard et al., 1961aFessard et al., , 1961b;;[START_REF] Albe-Fessard | Duality of unit discharges from cat centrum medianum in response to natural and electrical stimulation[END_REF][START_REF] Korn | Somatic projection to the orbital cortex of the cat[END_REF]Massion et al., 1965aMassion et al., , 1965b) ) . In 1961, she began to collaborate with Gérard Guiot (1912Guiot ( -1998)), a neurosurgeon at the Foch hospital in Paris metropolitan area and recorded, after craniotomy, the evoked potentials and the unitary neuron responses in the thalamus of parkinsonian patients who have had thalamotomy. In the mean time, she obtained new results on the mechanisms of pain and somatic representations in the human thalamus [START_REF] Albe-Fessard | La douleur : ses mécanismes et les bases de ses traitements[END_REF][START_REF] Iggo | Somatosensory system[END_REF][START_REF] Albe-Fessard | Activités électriques caractéristiques de quelques structures cérébrales chez l'homme[END_REF], 1966a, 1966b[START_REF] Albe-Fessard | Thalamic unit activity in man[END_REF][START_REF] Berkley | Madame Albe-Fessard: a meaningful legacy[END_REF]Guiot et al., 1962aGuiot et al., , 1962b[START_REF] Guiot | Dérivations d'activités unitaires en cours d'intervention stéréotaxiques[END_REF]. She then focused her research on the thalamus and studied its intralaminar nerve nets in monkeys. Her activity at Marey Institute allowed several of her students to pursue a very successful career [START_REF] Chalazonitis | Abnormal neuronal discharges[END_REF][START_REF] Massion | Influence du cervelet sur les différentes composantes de la réponse corticale primaire somatique chez le chat anesthésié au chloralose[END_REF][START_REF] Naquet | Ralentissements et accélérations de l'activité corticale obtenus par refroidissement localisé de la formation réticulée mésencéphalique du chat éveillé[END_REF].

Figure legends

Figures

  Figures and Institutions of the neurological sciences in Paris from 1800 to 1950. Part II: Neurophysiology

Figure 1 .

 1 Figure 1. Picture of Magendie. Portrait de Magendie (©BIU Santé).Figure 2. Picture of Flourens. Portrait de Flourens (Académie Nationale de Médecine). Figure 3. Reproduction of the title page of the famous 1824 Flourens treatise. Reproduction de la page de titre du célèbre traité de 1824 de Flourens.Figure 4. Picture of Claude Bernard. Photographie de Claude Bernard (©BIU Santé).Figure 5. Picture of Brown-Séquard. Photographie de Brown-Séquard (©BIU Santé) Figure 6. Picture of Marey. Photographie de Marey (©BIU Santé) Figure 7. Marey's myograph used in measuring muscle contraction in frog. Myographe de Marey utilisé pour mesurer la contraction musculaire chez la grenouille (©BIU Santé) Figure 8. Picture of Alfred Fessard and of his wife Denise Albe-Fessard. Photographie d'Alfred Fessard et de son épouse Denise Albe-Fessard. (Fonds Jean Fessard with permission).

Figure 2 .

 2 Figure 1. Picture of Magendie. Portrait de Magendie (©BIU Santé).Figure 2. Picture of Flourens. Portrait de Flourens (Académie Nationale de Médecine). Figure 3. Reproduction of the title page of the famous 1824 Flourens treatise. Reproduction de la page de titre du célèbre traité de 1824 de Flourens.Figure 4. Picture of Claude Bernard. Photographie de Claude Bernard (©BIU Santé).Figure 5. Picture of Brown-Séquard. Photographie de Brown-Séquard (©BIU Santé) Figure 6. Picture of Marey. Photographie de Marey (©BIU Santé) Figure 7. Marey's myograph used in measuring muscle contraction in frog. Myographe de Marey utilisé pour mesurer la contraction musculaire chez la grenouille (©BIU Santé) Figure 8. Picture of Alfred Fessard and of his wife Denise Albe-Fessard. Photographie d'Alfred Fessard et de son épouse Denise Albe-Fessard. (Fonds Jean Fessard with permission).

Figure 4 .

 4 Figure 1. Picture of Magendie. Portrait de Magendie (©BIU Santé).Figure 2. Picture of Flourens. Portrait de Flourens (Académie Nationale de Médecine). Figure 3. Reproduction of the title page of the famous 1824 Flourens treatise. Reproduction de la page de titre du célèbre traité de 1824 de Flourens.Figure 4. Picture of Claude Bernard. Photographie de Claude Bernard (©BIU Santé).Figure 5. Picture of Brown-Séquard. Photographie de Brown-Séquard (©BIU Santé) Figure 6. Picture of Marey. Photographie de Marey (©BIU Santé) Figure 7. Marey's myograph used in measuring muscle contraction in frog. Myographe de Marey utilisé pour mesurer la contraction musculaire chez la grenouille (©BIU Santé) Figure 8. Picture of Alfred Fessard and of his wife Denise Albe-Fessard. Photographie d'Alfred Fessard et de son épouse Denise Albe-Fessard. (Fonds Jean Fessard with permission).

Figure 5 .

 5 Figure 1. Picture of Magendie. Portrait de Magendie (©BIU Santé).Figure 2. Picture of Flourens. Portrait de Flourens (Académie Nationale de Médecine). Figure 3. Reproduction of the title page of the famous 1824 Flourens treatise. Reproduction de la page de titre du célèbre traité de 1824 de Flourens.Figure 4. Picture of Claude Bernard. Photographie de Claude Bernard (©BIU Santé).Figure 5. Picture of Brown-Séquard. Photographie de Brown-Séquard (©BIU Santé) Figure 6. Picture of Marey. Photographie de Marey (©BIU Santé) Figure 7. Marey's myograph used in measuring muscle contraction in frog. Myographe de Marey utilisé pour mesurer la contraction musculaire chez la grenouille (©BIU Santé) Figure 8. Picture of Alfred Fessard and of his wife Denise Albe-Fessard. Photographie d'Alfred Fessard et de son épouse Denise Albe-Fessard. (Fonds Jean Fessard with permission).

Acknowledgements

The authors would like to thank for their tremendous help Chloé Loiraud, Yann Bregeras, Sandrine Jamen and Jessica Moreau from Bibliothèque Médicale, Hôpital Neurologique Pierre Wertheimer, Lyon, France, Chantal Barbara, Marjorie Lorch (ISHN), the École des Neurosciences de Paris, the Club d'Histoire des Neurosciences from the Société des Neurosciences and the BIU Santé (Bibliothèque Inter Universitaire de Santé de Paris) and the Académie Nationale de Médecine and Académie des Sciences for the reproduction of photographs.

Conflicts of interest : none