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1 53 2 54 3 C. R. Biologies ••• (••••) •••–••• 55 4 http://france.elsevier.com/direct/CRASS3/ 56 5 57 6 Neurosciences 58 7 59 8 The physiological construction of the neurone concept (1891–1952) 60 9 61 10 Jean-Gaël Barbara 62 11 63

12 ‘Recherches épistémologiques et historiques sur les sciences exactes et les institutions scientifiques’ (REHSEIS), CNRS UMR 7596, 64 13 ‘Neurobiologie des processus adaptatifs’, CNRS UMR 7102, université Pierre-et-Marie-Curie, 65 14 7, quai Saint-Bernard, case 14, 75252 Paris cedex 05, France 66 15 Received 15 November 2005; accepted after revision 15 February 2006 67 16 68 17 69 Presented by J.-M. Blengino 18 70 19 71 20 72 21 Abstract 73 22 Steps in the physiological construction of the neurone concept are described. Early ideas on the function of the nerve cell led 74 23 to later polemics on the neurone doctrine and the speculative attitude of histophysiology. Researches of Sherrington and Adrian 75 24 emerged from a specific British context, and confronted American oscillography and Berger rhythm. At the end of various polemics, 76 25 the neurone was constructed by the intracellular technique and the use of concepts borrowed from other sub-disciplines. Analysis 77 26 of these paths demonstrates underlying disciplinary interactions as essential factors. To cite this article: J.-G. Barbara, C. R. 78 27 Biologies ••• (••••). 79  28 2006 Académie des sciences. Published by Elsevier SAS. All rights reserved. 80 29 Résumé 81 30 Construction physiologique du concept de neurone (1891–1952). Les étapes de la construction physiologique du concept de 82 31 neurone sont décrites. Les idées initiales sur la fonction de la cellule nerveuse aboutissent aux polémiques sur la théorie du neurone 83 32 et les prétentions spéculatives de l’histophysiologie. Les programmes de recherche de Sherrington et Adrian émergent d’un contexte 84 33 britannique spécifique et se confrontent à l’oscillographie américaine et au rythme de Berger. Au terme de polémiques multiples, le 85 34 neurone se constitue par la technique intracellulaire et l’incorporation de concepts issus d’autres sous-disciplines. L’analyse de ces 86 35 voies démontre les interactions entre disciplines sous-jacentes comme des facteurs essentiels. Pour citer cet article : J.-G. Barbara, 87 36 C. R. Biologies ••• (••••). 88  37 2006 Académie des sciences. Published by Elsevier SAS. All rights reserved. 89 38 Keywords: Neurone concept; Disciplines; Neurone doctrine; Histophysiology; Electrophysiology 90 39 91 Mots-clés : Concept de neurone ; Disciplines ; Théorie du neurone ; Histophysiologie ; Électrophysiologie 40 92 41 93 42 94 43 1. Introduction tween nerve fibres and the soma of nerve cells. The 95 44 UNCORRECTEDneurone conceptPROOF of Heinrich Waldeyer (1836–1921) [1] 96 45 The classical presentation of the neurone doctrine de- was established upon topography of sub-cellular ele- 97 46 scribes main achievements and controversies over dif- ments such as dendrites, somata, nuclei, fibrils, and ax- 98 47 99 ferent techniques and interpretations of relations be- ons (1891). However, the idea of polarized functional 48 100 interactions between cell parts allowed a new interpre- 49 101 E-mail address: 50 [email protected] (J.-G. Barbara). tation of the neurone, which emphasized the role of the 102 51 1631-0691/$ – see front matter  2006 Académie des sciences. Published by Elsevier SAS. All rights reserved. 103 52 doi:10.1016/j.crvi.2006.03.014 104 ARTICLE IN PRESS JID:CRASS3 AID:2439 /FLA [m3+; v 1.59; Prn:29/03/2006; 15:59] P.2 (1-13) 2 J.-G. Barbara / C. R. Biologies ••• (••••) •••–•••

1 soma in the propagation of nerve impulse. The success parts of nerve cells, although anatomical and functional 53 2 of the neurone doctrine promoted further physiologi- continuity between them was assumed. Rather, cells 54 3 cal speculations with marked differences among Eu- were described as enlarged portions of fibres, unipolar, 55 4 ropean countries. The legitimacy of histology to com- bipolar or multipolar, depending on the number of fibres 56 5 ment on the function of nerve cells seemed to over- in contact [2]. Nerve cells were not considered neces- 57 6 lap that of physiology. Conversely, physiology inter- sary for the transmission of the nervous impulse through 58 7 acted with histology, when this discipline was able to ganglia, since most anatomists considered at least that 59 8 adopt, criticize and even rectify the neurone concept. some fibres were uninterrupted in crossing these struc- 60 9 However, physiologists differed in this attitude, espe- tures. However, multipolar nerve cells in the anterior 61 10 cially between Britain and France. A comparison of horn of spinal cord were seen as necessary connecting 62 11 physiological conceptions on nerve cells within partic- devices between sensory and motor impulses. In 1857, 63 12 ular contexts of reception and rectification of the neu- Claude Bernard (1813–1878) concluded: 64 13 rone doctrine is needed. Our goal is to establish how 65 14 different research programmes devoted to the nervous “D’après ce qui précède, on voit que les cellules 66 15 system emerged at the beginning of the 20th century. seraient tantôt l’origine des fibres nerveuses, tantôt 67 16 An implicit reference to the central role of the nerve des organules placés sur le trajet de ces fibres. On 68 17 cell in some programmes determined original paths in pourrait dans ces cas considérer les tubes comme 69 18 the careers of Charles Sherrington (1857–1952) and les conducteurs du système nerveux, dont les cel- 70 19 Edgar Douglas Adrian (1889–1977). British physiology lules seraient l’agent élaborateur ou collecteur.”[2 71 20 was more inclined than French or American to local- (pp. 127–128)]1 72 21 ize nervous properties in neuronal elements. Numerous 73 22 polemics arose between axonology, electroencephalog- Occasionally, some histologists and physiologists 74 23 raphy, and neurophysiology. Occasionally, they deter- criticized this simplistic view. The discovery by Louis- 75 24 mined heuristic syncretisms between distant research Antoine Ranvier (1835–1922) of the T structure of 76 25 77 programmes. These events finally led to the modern sensory neurones in dorsal root ganglia [3] established 26 78 neurone concept developed with intracellular recordings a new type of contact between fibres and nerve cells, 27 (1952). This paper aims at examining old rooted episte- 79 where the soma could neither be seen necessarily as a 28 mological problems that paralleled the construction of 80 collector, nor receptor. The British physiologist Michael 29 the neurone concept from 1891 to 1952. An emphasis is 81 Foster (1836–1907) also criticised the role assigned to 30 put on the role of pre-established scientific disciplines, 82 the soma. 31 sub-disciplines and their relations as important factors 83 32 contributing to the genesis of epistemological conflicts. 84 “[...] reflex action is carried on undoubtedly through 33 Conversely, resolutions and synthesis of different ap- 85 cells. But it does not follow that a cellular mechanism 34 proaches are seen as major determinants of conceptual 86 is essential in the sense at all events that the nuclei of 35 advances and redefinitions of disciplines. Therefore, the 87 the cells have anything to do with the matter [...]” [4] 36 history of the neurone concept gives us the opportu- 88 37 nity to ask some intermingled problems between social 89 Such criticisms were both ancient and common. 38 factors and epistemological knots in examining the re- 90 They supposed functional continuity between fibres 39 lations at work in the constructions of both disciplines 91 only relied on their anatomical continuity, with cells 40 and concepts. 92 41 considered as trophic centres. This view was already 93 held by the first French professor of histology at the 42 2. Consensus and initial discussions on the nerve 94 43 cell Parisian ‘Faculté de médecine’, Charles Robin (1821– 95 44 1885), a famous opponent of the cell theory [5 (p. 542)]. 96 45 Before the neurone doctrineUNCORRECTED was established, most In his work, PROOF the exclusion of cells as a general con- 97 46 physiologists and anatomists held a common view of stituent of tissues led to this early form of reticularism 98 47 nerve cells, considered as necessary loci of anatomical (1892): 99 48 interactions between fibres. Such conceptions referred 100 49 specifically to the soma of cells, located in the grey mat- 101 1 “From previous facts, [nerve] cells should either be the origin of 50 102 ter of nerve centres, as opposed to fibres and protoplas- fibres or organelles placed on fibre paths. In such cases, tubes would 51 mic processes. The nerve cell was occasionally termed represent conductors of the nervous system, with cells being a making 103 52 ‘nucleus’. In no way were nerve fibres understood as or a collecting agent.” 104 ARTICLE IN PRESS JID:CRASS3 AID:2439 /FLA [m3+; v 1.59; Prn:29/03/2006; 15:59] P.3 (1-13) J.-G. Barbara / C. R. Biologies ••• (••••) •••–••• 3

1 “Au-delà de l’état cellulaire, il y a l’état d’organisa- anatomopathology and physiology. In the 19th century, 53 2 tion ; [...] le mot cellule ne suffit pas, puisqu’il n’im- these disciplines were often associated in teaching, jour- 54 3 plique pas les états de fibre, de tube, états qui sont nals and scientific programmes. However (1), at the turn 55 4 tout aussi réels que l’état dit cellulaire.” [5 (p. 18)]2 of the 20th century, French Bernardian physiology de- 56 5 veloped into an independent discipline, which increas- 57 6 Conversely, the early cellularist anatomist Math- ingly rejected the concepts and methods of anatomy. 58 7 ias Duval (1844–1907), originally from the Strasbourg (2) These two aspects permeate and define French re- 59 8 school of histology, attributed a greater importance to actions to the neurone doctrine. 60 9 the cell, a view later adopted together with cell theory The first aspect mainly concerns those researchers 61 10 by Bernard at the ‘Collège de France’. Duval stated: who were interested both in anatomy, physiology and 62 11 their relations. The Strasbourg school of histology fol- 63 12 “Le rôle de la cellule nerveuse est de favoriser le pas- lowed this path before 1870, as it adopted microscopy 64 13 sage de l’excitation d’une fibre dans une autre : elle and cell theory. Duval, one of its young most talented 65 14 représente un centre de détente ; mais ce rôle peut scientists, took up the chair of Robin (1885). Duval at- 66 15 être très complexe ; ainsi souvent un premier globule tributed the general success of Santiago Ramón y Ca- 67 16 réfléchit l’action, par une fibre commissure, sur un ou jal’s (1852–1934) doctrine, versus the lesser impact of 68 17 plusieurs autres globules qui peuvent diriger diverse- Golgi Camillo’s (1843–1926) ideas, to the role gener- 69 18 ment à leur tour, directement sur une fibre centrifuge ally assigned to nerve cells in physiological studies of 70 19 proprement dite, ou d’abord sur de nouveaux glob- spinal cord reflexes [7 (pp. VIII–X)]. Hence, both phys- 71 20 ules nerveux [...]” [6 (p. 31)]3 iological and anatomical considerations were present 72 21 in the early appraisal of Ramón y Cajal’s findings and 73 22 Hence, the first conceptions of the nerve cell as a in the adoption of Golgi’s method by French histolo- 74 23 functional unit were related to the acceptance of the cell gists, including Duval, Edmond Retterer, Victor André 75 24 theory. Cornil, Léon Azoulay, Jean Nageotte, Georges Mari- 76 25 However, since physiology was essentially based on nesco, and René Legendre. 77 26 the study of nerves, physiologists considered that the As many of their European counterparts, French his- 78 27 anatomical architecture of fibres was a prime struc- tologists tended to progressively adopt physiological 79 28 tural determinant of function. Accordingly, discussions views. The histologist from Nancy Auguste Louis César 80 29 on the nerve cell remained quite similar to later ones Prenant (1861–1927) noticed the new physiological ori- 81 30 devoted to the neurone concept. Nevertheless, specific entations of Oscar Hertwig (1849–1922), director of the 82 31 reactions to the neurone doctrine in France and Great second Institute of anatomy of the Berlin University in 83 32 Britain influenced the debates on the nerve cell and the his book La Cellule et les Tissus [8]. Prenant followed 84 33 relations between histology and physiology. Cell theory this path, when he later discussed histological and phys- 85 34 was no longer crucial to the functional understanding of iological views on the role of nerve cells, and sought to 86 35 the neurone, nor in the reception of the neurone doc- define an uneasy consensus [9]. 87 36 trine. Rather the institutional relations between disci- However, some French and Belgian histologists de- 88 37 plines became dominant. veloped, apart from any syncretic position, a style in 89 38 histophysiology, following Max Schultze (1825–1874), 90 39 3. The reception of the neurone doctrine among Ranvier, and Ramón y Cajal, but focussing on a cellu- 91 40 French histologists lar approach to processes such as sleep, anaesthesia or 92 41 memory (Duval, Demoor, Lépine). This perspective was 93 42 vehemently attacked by physiologists including Köl- 94 French reception of the neurone doctrine highlights 43 liker or Lapicque, as stressed by René Legendre (1880– 95 two complex institutional relations between anatomy, 44 1954): 96 45 UNCORRECTED PROOF 97 46 2 “Beyond the cellular state lies the state of organization; [...] the “[La théorie du neurone] eut un très grand suc- 98 47 word cell does not suffice, since it does not imply states of fibres, cès [...] elle suscita diverses hypothèses ingénieuses, 99 48 tubes which are as real as that termed cellular.” tant physiologiques que pathologiques et même psy- 100 3 49 “The role of the nerve cell is to favour the passage of excitation chologiques [...] on imagina le point de contact de 101 from a fibre to another: it represents a trigger centre; however, this 50 [ ] 102 role may be more complex; thus, a first globule often reflects action deux neurones comme un commutateur ... , la com- 51 by way of a commissural fibre on one or many globules that diversely mutation étant établie par amœbisme, plasticité ou 103 52 direct it on a centrifugal fibre or first on other nervous globules.” hypertrophie fonctionnelle [...] Ces théories eurent 104 ARTICLE IN PRESS JID:CRASS3 AID:2439 /FLA [m3+; v 1.59; Prn:29/03/2006; 15:59] P.4 (1-13) 4 J.-G. Barbara / C. R. Biologies ••• (••••) •••–•••

1 un grand succès, en France principalement. Cepen- Great Britain, cellular theory encountered fewer obsta- 53 2 dant elles furent violemment critiquées – avec juste cles than in France, but it was nevertheless criticized in 54 3 raison – par divers auteurs. [...] ces théories [...] developmental studies [12–14]. In 1891–1892, Golgi’s 55 4 sont en quelque sorte, l’exagération de la théorie du staining method was brought to attention with translated 56 5 neurone [...]” [10 (p. 244)]4 studies from Ramón y Cajal, Arthur Van Gehuchten 57 6 (1861–1914), Rudolf Albert von Kölliker (1817–1905) 58 7 Duval’s theory of sleep was the most famous French and Luigi Sala (1863–1930) edited in the Journal of 59 8 histophysiological theory [11]. It emerged from the Anatomy and Physiology. 60 9 ideas of Hermann Rabl-Rückhard (1839–1905) and However, between 1891 and 1900, few British his- 61 10 contemporary histopathological studies by Raphaël tologists worked extensively with the new techniques, 62 11 Lépine (1840–1919). It posited that contacts between apart from some observations on invertebrates, neu- 63 12 neurones were less numerous during sleep and reap- roglia and ganglionic cells. Rather, the histology of the 64 13 peared on waking by cell motility. Many histologists nervous system was dominated by topographical studies 65 14 considered retraction of neuronal elements only oc- of nerve supplies to organs at a larger scale, emphasiz- 66 15 curred in experimental and pathological conditions and ing the gross functional organization of nerves from a 67 16 physiologists considered this theory a naive anatomical physiological perspective. This specific context eventu- 68 17 determinism of nervous pathways, relying on pure spec- ally proved successful in adopting and discussing on 69 18 ulations, a view adopted by Ramón y Cajal himself. solid scientific grounds the neurone doctrine between 70 19 However, this radical attitude of French histology re- histological facts and physiological measurements. 71 20 flected the increasing gap between its style of reasoning This context is highlighted by the famous collabo- 72 21 and that of French physiology, which sought to escape ration between physiologist George Romanes (1848– 73 22 anatomy by any means. This over speculative attitude 1894) and histologist Edward Sharpey-Schäfer (1850– 74 23 of part of French histophysiology cannot be seen today 1935). This episode provides an excellent example of 75 24 as totally naive or wrong. The finding that the number British multidisciplinary relations in the context of Fos- 76 25 of dendritic spines was reduced on exposure to toxic ter’s young school of physiology, finally permeable to 77 26 agents was generally regarded by contemporaries as a the novel idea that nerve fibres were independent struc- 78 27 scientifically established fact. However, the absence of tures functioning physiologically as a whole [15,16]. 79 28 direct experimental support for some histophysiological Romanes, one of Foster’s first pupils, studied locomo- 80 29 theories such as Duval’s one contributed to the dismissal tion of jelly fish. He adopted a ganglionic theory close 81 30 of histological approaches by leading French physiolo- to his master’s on heart beat. When he could not localize 82 31 gists. nervous elements in jelly fish, Romanes asked his friend 83 32 for help. This led Sharpey-Schäfer to discover free fi- 84 33 4. Specificity of the context of reception of the bre endings in the margin of jelly-fish and conclude in 85 34 neurone doctrine and its rectification in Great favour of physiological continuity of discontinuous fi- 86 35 Britain bres [17]. 87 36 These events were analysed from the standpoint of 88 37 As compared to France, British microscopical sci- the neurone doctrine, showing how Sharpey-Schäfer 89 38 ences encompassed a more uniform field of enquiry became one of its prominent British forerunners [15, 90 39 including anatomopathology, comparative histology 16 (p. 47)]. Sharpey-Schäfer himself felt his 1878 pa- 91 40 of plants and animals, human histophysiology, topo- per was the first demonstration of contiguity between 92 41 graphic anatomy. It gained full academic recognition nerve cells [15 (p. 160)]. However, the specificity of 93 42 with the foundation of the Quarterly Journal of Mi- the British reception of the neurone doctrine did not 94 43 croscopical Science, founded some 43 years before the rely in Schäfer’s discovery, but was shaped by close 95 44 French Archives d’anatomie microscopique (1897). In relations among physiologists and histologists, and the 96 45 UNCORRECTEDanatomical PROOF background of many physiologists. When 97 46 4 “The neurone theory had a great success [...]. Ingenious phys- Sharpey-Schäfer demonstrated free nerve endings in 98 47 iological, pathological and even psychological hypotheses emerged jelly-fish, other studies using the gold staining tech- 99 48 [...]. The point of contact between two neurones was regarded as a niques of Julius Cohnheim (1839–1884) and Joseph von 100 49 switch established by amœbism, plasticity or functional hypertrophy Gerlach (1820–1896) [18] allowed investigators from 101 [...]. These theories had a great success, mainly in France. However, 50 102 they were vehemently, and rightly, attacked by various authors [...], other countries to clearly refute fibre nets [19–21]. Fur- 51 these theories represent some sort of exaggeration of the theory of the thermore, the statements of Sharpey-Schäfer on the con- 103 52 neurone.” tiguity of fibres were received sceptically by contempo- 104 ARTICLE IN PRESS JID:CRASS3 AID:2439 /FLA [m3+; v 1.59; Prn:29/03/2006; 15:59] P.5 (1-13) J.-G. Barbara / C. R. Biologies ••• (••••) •••–••• 5

1 rary reports [15 (p. 160)], including one from Romanes. nally adopting Sherrington’s view [30 (p. 196)]. Hence, 53 2 Hence, Sharpey-Schäfer’s ideas should not be seen as the histological orientation of Sherrington and his close 54 3 the “first clear statement of the neurone theory” [22 contacts with Ramón y Cajal were crucial in the British 55 4 (p. 246)]. More important seemed Sharpey-Schäfer’s in- adoption and rectification of the neurone concept in 56 5 fluence in convincing his friend Romanes, who had ini- Britain. 57 6 tially written critically to Sharpey-Schäfer (1877) [15 58 7 (p. 162)]. For Romanes, physiological continuity of 5. Rejection of the neurone concept as a 59 8 jelly-fish contractile elements was based on coordinated physiological unit in France (1900) 60 9 activities of lithocysts, considered as analogous to gan- 61 10 glia. Romanes finally adopted Sharpey-Schäfer’s views, Sherrington’s personal appraisal of the neurone indi- 62 11 explaining in 1885 his conception of physiological con- cated a new tendency in the 1890s among physiologists 63 12 tinuity by a “physiological induction” between distinct to react to a pure histological concept and its histophys- 64 13 fibres [23]. Therefore, a continuous and profitable dia- iological corollaries. By 1900, physiology was devel- 65 14 logue between physiology and histology seemed possi- oping new programmes in physical physiology, phys- 66 15 ble in Britain, whereas both disciplines were both more iological chemistry both in Britain, France and Ger- 67 16 specialized and independent in France. many. Physiology was becoming increasingly emanci- 68 17 Such relations were pursued during the 1890s be- pated from anatomy. However, if British physiologists 69 18 tween Sherrington, Sharpey-Schäfer, and Ramón y Ca- retained close links with anatomy, their French coun- 70 19 jal. When Sharpey-Schäfer reviewed the neurone doc- terparts abandoned fundamental studies on reflexes and 71 20 trine [24], Sherrington was not only concerned with his adopted a physicochemical approach to life and nerve 72 21 first physiological studies of the spinal cord, but also functions. The career of Albert Dastre (1844–1917), 73 22 with anatomopathological and histological observations professor of physiology at the Sorbonne, illustrates this 74 23 of fibres, and nerve cells. In 1894, Sherrington invited orientation. As a student of Bernard, Dastre studied 75 24 Ramón y Cajal to give the Croonian Lecture entitled vasomotor reflexes according to Étienne-Jules Marey’s 76 5 25 La fine structure des centres nerveux [25,26]. Much (1830–1904) techniques, before developing chemical 77 26 emphasis has been placed on Sherrington’s adoption analysis of coagulation, liver pigments, or gelatine. No- 78 27 in 1897 of the term synapse [27,28], in the success- bel Prize Charles Richet (1850–1935) also abandoned 79 28 ful confrontation of the histological law of the dynamic nervous and muscular physiology to adopt a physic- 80 29 polarization of the neurone with recordings of spinal ochemical programme on stomach secretions, animal 81 30 cord antidromic evoked potentials [29]. However, it heat and serotherapy. Auguste Chauveau (1827–1917) 82 31 should be stressed that this adoption did not concern any worked on cardiac contraction with Marey before devel- 83 32 key discovery, but rather indicated again a specifically oping in the 1890s energetics as a French physiological 84 33 British histological concern in physiology. Berlucchi discipline. 85 34 clearly noted that Sherrington’s experimental demon- Consequently, French nervous physiology, while 86 35 stration of the possibility of antidromic conduction in adopting the neurone doctrine, centred both experimen- 87 36 the spinal cord was based on a refined correlation be- tal approaches and theoretical interests on the study of 88 37 tween possible anatomically defined paths for nervous nerves, rejecting the neurone as a functional entity of 89 38 impulse and their electrophysiological demonstration physiological interest. Dastre vividly attacked anatomy 90 39 by precise electrical stimulations [30]. However, exper- and thought the neurone concept was of no utility in 91 40 imental antidromic conduction was a rather old theme the comprehension of the general properties of the ner- 92 41 of nerve physiology, which had inspired work by Emil vous system. The nature of the nervous impulse and the 93 42 du Bois-Reymond (1818–1896), Wilhelm Friedrich determinism of its propagation in various paths should 94 43 Kühne (1837–1900), Aleksandr Ivanovich Babukhin be investigated by physicochemical means. The article 95 44 [Babuchin] (1835–1891), Edmé Félix Alfred Vulpian published by Jean-Pierre Morat (1846–1920), a collabo- 96 45 (1826–1887), and Paul Bert (1833–1886).UNCORRECTED In the con- rator of Dastre PROOF and professor of physiology in Lyons, on 97 46 text of the neurone doctrine, the data from Sherrington the nervous system and animal chemistry illustrated this 98 47 clearly showed that the long-known physiological po- reductionist attitude. However, he reverted to a more 99 48 larization of conduction in the spinal cord was not a classical view in a subsequent article published in 1909 100 49 property of nerve trunks, but rather was localised either [31]: 101 50 in the soma of nerve cells or in theirs junctions with 102 51 fibres. Berlucchi has pointed out how Ramón y Cajal 5 A 2006 issue of Comptes rendus Palevol is devoted to Étienne- 103 52 changed his mind on the polarization of the neurone, fi- Jules Marey’s death centennial [65]. 104 ARTICLE IN PRESS JID:CRASS3 AID:2439 /FLA [m3+; v 1.59; Prn:29/03/2006; 15:59] P.6 (1-13) 6 J.-G. Barbara / C. R. Biologies ••• (••••) •••–•••

1 “[...] si à l’exemple du chimiste, qui ne peut agir However, Lapicque envisaged these properties not 53 2 sur les molécules isolées du corps qu’il étudie, in an anatomical framework, but rather from that of 54 3 nous ne pouvons interroger individuellement les fi- the physical possibility of transmission between two 55 4 bres composantes des nerfs que nous expérimen- nervous elements dependent on a similar excitability 56 5 tons, nous avons néanmoins sur lui l’avantage de (chronaxie). Therefore, Sherrington’s and Lapicque’s 57 6 voir nos éléments à nous par les méthodes his- views were opposed in the importance attributed to 58 7 tologiques et de leur reconnaître ainsi certains car- the soma and elementary fibres. Sherrington supposed 59 8 actères empiriques, qui les distinguent en catégorie.” that nervous impulses converged on central nerve cells, 60 9 [31 (p. 671)]6 anatomically connected to afferent fibres, whose activ- 61 10 ity imposed a central delay and a polarity of nervous 62 11 However, while French physiologists unequivocally conduction. Conversely, Lapicque understood nervous 63 12 adopted the neurone doctrine and considered the nerve impulse conduction as determined not only by anatom- 64 13 cell as an anatomical unit, nervous functions were rather ical connections of fibres, but more importantly by the 65 14 seen as relevant to the intimate nature of fibres. This tuning of physical properties controlled by higher cen- 66 15 idea led to the ancient refusal to attribute any specific tres, between functionally continuous elements. 67 16 physiological role except a trophic function to the soma Lapicque’s conceptions are often presented as old 68 17 of nerve cells, in accordance with the doctrine of Au- dogmas established on the basis of chronaxie measure- 69 18 gustus Volney Waller (1816–1870). Energy, substance, ments in the early 20th century, which induced a paral- 70 19 movement, life were seen as equally scattered entities ysis in French physiology for over three decades [33]. 71 20 in the nervous system, which underlined non-localised It should be emphasized that Lapicque’s character was 72 21 functions. Therefore, the distribution of nerve cells in of fundamental importance in this period. However, the 73 22 the nervous system was not central. Rather, the topog- development of a Lapicquian physiology can be traced 74 23 raphy of fibres and their physical interactions were con- to the rejection of the neuronal soma as a physiological 75 24 sidered as the essential factors in nerve cell excitation. element starting in the 1880s. Lapicque later developed 76 25 Louis Lapicque (1866–1952), a student of Dastre a grand theory of nervous functions rejecting anatomy 77 26 and the neurone concept. His attitude finally led to the 78 and leader of French neurophysiologists between the 27 full dismissal of his highly speculative ideas. Thus, the 79 two world wars, developed these ideas into a concerted 28 functionalist attitude of Lapicque may represent an op- 80 theoretical system based on single nerve studies. In ac- 29 posite extreme to Duval’s programme of histophysiol- 81 cordance with his purely physiological and speculative 30 ogy. 82 views, Lapicque adopted the synapse of Sherrington as 31 83 a physiological concept based on polarization, delay and 32 6. Sherrington’s myographic decomposition of 84 an anatomical determinism of neurotransmission. 33 nerve centres and the neurone as a physiological 85 34 concept (1900–1926) 86 “[...] c’est à la synapse qu’est localisée la fonc- 35 87 tion essentielle du centre nerveux [...] Sherrington 36 The comparison between Sherrington’s and Lapic- 88 a donné un résumé, remarquable dans sa concision, 37 que’s ideas on the neurone can be seen as a diver- 89 des différences essentielles qui distinguent de la sim- 38 gence from an initial criticism by physiologists of the 90 ple propagation dans un tronc nerveux le passage de 39 nerve cell in the late 1880s. However, in his personal 91 l’influx par les centres, et il a montré que presque 40 researches Sherrington created a dialogue between his- 92 toutes ces différences peuvent se caractériser de la 41 tology and physiology that focussed on specific objects 93 façon suivante : transmission intercellulaire au lieu 42 and concepts, including the flexor reflex, summation 94 de transmission intracellulaire [ ] 7 43 ... ” [32 (p. 106)] and the convergence of nervous impulses. This style 95 44 of research was based on a systematic topographical 96 45 UNCORRECTEDand functional PROOF approach of specific reflexes and on the 97 6 “If, as the chemist unable to act on isolated molecules from the 46 body he studies, we cannot study individual fibres forming the nerves localization of nervous properties in centres and their 98 47 on which we experiment, we do have the advantage over him to be neuronal constituents. 99 48 able to see our elements by histology and so to recognize in them Sherrington relied more on anatomy than on modern 100 49 some empiric characters that let us categorise them.” physical measurements. When Herbert Gasser (1888– 101 7 “[...] the essential function of nervous centre is localised at the 50 102 synapse [...] Sherrington gave a remarkably concise summary of es- 51 sential differences which distinguish simple propagation in a nervous showed that almost all these differences can be characterised as so: 103 52 trunk from the passage of nervous impulse through a centre and he intercellular transmission in place of intracellular transmission.” 104 ARTICLE IN PRESS JID:CRASS3 AID:2439 /FLA [m3+; v 1.59; Prn:29/03/2006; 15:59] P.7 (1-13) J.-G. Barbara / C. R. Biologies ••• (••••) •••–••• 7

1 1963) adopted oscillography in the early 1920s to Both Lucas and Sherrington agreed that nerve con- 53 2 analyse specific nerve fibre properties, Sherrington used duction differed from the passage of nervous impulses 54 3 the techniques of Marey, and his follower Charles Emile in centres. Lucas saw conduction in nerve trunks as 55 4 François-Franck (1849–1921) to decompose elemen- stereotyped and lacking properties such as inhibition, 56 5 tary reflex properties. Sherrington was interested in the rhythms, residual discharges which enabled centres to 57 6 neurone as a principal physiological element for how it adapt their activity [36 (p. 8)]. However, he did not 58 7 might assist his attempts to dissect the reflex centre of follow Sherrington in locating such complex properties 59 8 the flexor reflex [34]. The conjunction of the neurone in non-nervous elements, which the Cambridge school 60 9 theory within Sherrington’s framework, as analysed by recognised as nerve cells. Lucas felt these differences 61 10 Swazey, relied on the belief that both inhibitory and fa- reflected ignorance of elementary mechanisms of con- 62 11 cilitatory mechanisms, earlier known as Hemmung and duction in nerve fibres [36 (p. 8)] and so emphasized 63 12 Bahnung in the German literature, contributed to cen- such studies initiated by Max Verworn (1863–1921) and 64 13 tral operations of coordination, taking place before a Friedrich Wilhelm Fröhlich (1879–1932). 65 14 common path of nerve fibres converged on an effector In this perspective, Adrian’s programme was aimed 66 15 muscle [35 (pp. 100–101)]. According to the schematic in the 1920s at deriving elementary properties of single 67 16 demonstration of Sherrington’s 1926 article, the total fibre activity with the idea of the possible all-or-none 68 17 amount of contraction of a muscle, obtained by stim- nature of the propagated nervous disturbance. In spite 69 18 ulating successively individual nerves independently, of Lucas’ idea and after World War I, Adrian collab- 70 19 71 was greater than the maximum contraction of that same orated with Cambridge school physiologists Alexander 20 72 muscle by direct stimulation. This was interpreted as Forbes (1882–1965), James Montrose Duncan Olmsted 21 73 a partial occlusion of nervous impulses from different (1886–1956) on spinal reflexes. The convergence of an 22 74 nerves converging on common motoneurones. Simi- in vivo approach with recordings of elementary sen- 23 75 larly, the facilitatory effect of a subliminal stimulation, sory fibre activities was necessary for both their spa- 24 76 in a given path, on the contraction obtained by stimu- tial and temporal decompositions. Dissection to single 25 77 lating another path was interpreted in terms of a central fibres and the in vivo temporal dispersion of their ac- 26 78 excitatory state in motoneurones. For Sherrington, neu- tivities were two necessary conditions to measure trains 27 rones were the cellular basis of coordination in the ner- 79 28 of spikes, adaptation and refractory periods in single fi- 80 vous system. They were for the first time given a prime bres. Adrian interpreted refractory periods of different 29 physiological importance on experimental grounds. 81 30 durations in two ways. First, following Lucas, long pe- 82 31 riods of refractoriness could depend on slow conduction 83 32 7. Adrian’s physiological foundation of the neurone in non-myelinated portions of a fibre, or be localised 84 33 (1926–1929) according to the Cambridge school in non-nervous ele- 85 34 ments, such as end-organs of sensory fibres [37].Only 86 35 Compared to Sherrington’s views, the neurone con- subsequently did Adrian finally adopt the second view 87 36 cept developed in the 1920s by Adrian was more than and localise a property measured in isolated single fibres 88 37 a speculative entity. It relied on precise instrumental in a motoneurone soma [38]. The comparison of sin- 89 38 objectivations. However, Adrian’s initial approach, fol- gle activities in sensory and motor fibres led Adrian to 90 39 lowing that of his teacher Keith Lucas (1879–1916), suppose that the essential neuronal element was perhaps 91 40 focussed on understanding the nature of nervous im- not the soma itself, but rather the dendritic expansions 92 41 pulse. Adrian’s physiological foundation of the neurone in contact with a nervous terminal arborisation. 93 42 borrowed from the differing orientations of Sherring- 94 43 ton and Lucas. Their programmes must be first con- “The only structural factors common to the sense 95 44 fronted to highlight the heuristic value later emerging organ and the motor nerve cell appear to be the termi- 96 45 from their dialogue. In a sense,UNCORRECTED Adrian’s approach was nal (axonal) PROOF arborisation which links the axon of the 97 46 a convergence between one approach based on anatom- sensory fibre with the sense organ, and that which 98 47 ical grounds and speculation, and the other grounded in invests the nerve cell or forms the junction zone 99 48 spatio-physicochemical explanations of the properties between its dendrites and the axons of others neu- 100 49 of isolated nerve axons. Comparison with France is no rones.” [39 (p. 145)] 101 50 longer fruitful, since convergences between anatomo- 102 51 clinical investigations and nerve studies focussed on “[...] the resemblance between the discharges of 103 52 medical rather than neurophysiological questions. sense organs and of motor neurones [...] has sug- 104 ARTICLE IN PRESS JID:CRASS3 AID:2439 /FLA [m3+; v 1.59; Prn:29/03/2006; 15:59] P.8 (1-13) 8 J.-G. Barbara / C. R. Biologies ••• (••••) •••–•••

1 gested that both are determined by some general plex spatial and temporal summations of elementary 53 2 property of the dendritic expansion.” [40 (p. 139)] potentials from homogenous populations of fibres [42]. 54 3 Eccles’ first paper on ganglia adopted the same ap- 55 4 “[...] the simplest alternative is to suppose that the proach: 56 5 rhythmic discharge actually starts in the terminal ar- 57 6 borizations of the sense organ and in some part of the “four corresponding groups of preganglionic fibres 58 7 motor nerve cell or its dendrites.” [39 (p. 150)] [which] may be distinguished from one another by 59 8 [...] [the] rates of preganglionic conduction, [...] 60 9 This view was developed in accord with the concept thresholds, [...] refractory periods [...] Presumably 61 10 of the synapse and with the idea of chemical trans- the four groups of preganglionic fibres differ only in 62 11 mission. Adrian’s microphysiology of nervous activities regard to size and medullation [...]” [43 (pp. 202– 63 12 had thus created a neurone concept based on localisa- 203)] 64 13 tions of fibre properties in neuronal parts, within a wide 65 14 theoretical framework. This analysis was in accord with Bishop and Hein- 66 15 Adrian’s neurone concept developed further in stud- becker who found no sign of central properties: 67 16 ies on retina, where interactions between photorecep- 68 17 tors and dendritic arborisation of ganglion cells could “[...] we find no spread of response from one cell 69 18 be analysed topographically. Such analysis recalls that to another, no after-discharge, and no summation 70 19 of Sherrington’s on the convergence of nerve fibres on of preganglionic impulses in the ganglion, although 71 20 a common motoneurone pool. Adrian showed that the more fibers emerge from it than enter.” [42 (p. 532)] 72 21 maximum retinal surface exposed to light from which a 73 22 single ganglion cell could be excited was wider than the However, a controversy emerged on the interpreta- 74 23 area of its dendritic expansion [38,41]. Thus, light re- tion of the refractory period of output compared to in- 75 24 ceptors and the excited nervous network beneath were put fibres. Eccles showed the slow value measured by 76 25 converging onto individual ganglion cells. Therefore, Bishop was much reduced in oxygenated and super- 77 26 Adrian had succeeded in defining experimentally Sher- fused ganglia. Hence, Eccles suggested its neuronal ori- 78 27 rington’s common path at the cellular level. gin, in agreement with the old finding that centres were 79 28 more sensitive to anoxia than nerve trunks. In spite of 80 29 8. Eccles’s studies on ganglia and further neuronal Rafael Lorente de Nó’s (1902–1990) apparent dismissal 81 30 localizations in the Cambridge school of this view, based on the similarity between input and 82 31 output refractory periods, Eccles and the Cambridge 83 32 The synthesis of ideas from Adrian and Sherrington school relied on small differences in refractory period 84 33 who jointly won the 1932 Nobel Prize led to a wide field to support their opinion that output potentials reflected 85 34 of inquiry which rapidly adopted oscillography for elec- the passage of the nervous impulse through neuronal so- 86 35 trophysiological studies. The Cambridge school, tend- mata. 87 36 ing to localize nervous properties into neurones, was 88 37 exposed to American researches which aimed to distin- “[...] the absolute refractory period of the motoneu- 89 38 guish fibres by their specific individual properties. rones (dendrites and body including the synapses) 90 39 Two different implicit epistemological choices were cannot be longer than 0.6 ms, which is the absolutely 91 40 available. Should correlations between elementary po- refractory period of the stimulated fibres themselves. 92 41 tentials and anatomy be interpreted according to dis- The present evidence neither excludes nor proves the 93 42 tinct fibre types or to the central topography of neuronal existence of a relatively refractory period of the neu- 94 43 somata. In the early 1930s, many investigators includ- rone body. It is suggested that the perikaryon func- 95 44 ing George Holman Bishop (1889–1973), Peter Hein- tions in the same way as the muscle endplate [...]” 96 45 becker (1895–1967), John CarewUNCORRECTED Eccles (1903–1997), [44 (p. PROOF 288)] 97 46 Detlev Wulf Bronk (1897–1975), Jean Govaerts, David 98 47 Lloyd (1911–1985), Sixto Obrador (1911–1978), José The Cambridge school later objectivated neurones 99 48 Bernardo Odoriz (1908) and David Whitteridge (1912– according to correlations between the topography of 100 49 1994) realized such correlations required the study of slow potentials and neuronal ganglionic somata. Again, 101 50 simple nervous structures such as ganglia. Bishop’s Eccles’ study relied on American oscillography, and 102 51 1932 paper was the first of this kind, where oscillo- especially Gasser’s studies of slow after-potentials 103 52 graphic potentials in ganglia were interpreted as com- recorded from isolated nerves. Gasser considered after- 104 ARTICLE IN PRESS JID:CRASS3 AID:2439 /FLA [m3+; v 1.59; Prn:29/03/2006; 15:59] P.9 (1-13) J.-G. Barbara / C. R. Biologies ••• (••••) •••–••• 9

1 potentials resulted from molecular and metabolic states on ganglia. The axonologist Lorente de Nó further stud- 53 2 of nerve’s plasma membrane. Conversely, Eccles ied the involvement of internuncial neurones in oculo- 54 3 showed that slow waves, either positive or negative, motor ganglia. His initial oscillographic measurements 55 4 were larger when recorded closer to ganglionic neu- of refractory periods had led him to adopt an aggressive 56 5 rones. Correlations between the polarity of these waves attitude and a strange interpretation of nervous centres 57 6 and facilitation between successive stimuli led him to relying on old criticisms of the nerve cell, reminiscent 58 7 suggest that slow potentials were generated inside neu- of his histological background from Ramón y Cajal’s 59 8 ronal somata, and reflected the central excitatory (c.e.s.) school: 60 9 or central inhibitory states (c.i.s.) of Sherrington. This 61 10 attitude was severely judged as a speculative localiza- “[...] evidence has been forthcoming which changes 62 11 tion of neuronal properties by axonologists, a group of the theoretical basis upon which the Oxford school 63 12 scientists formed by Alexander Forbes (1882–1965) et based the discussion of the experimental findings.” 64 13 Ralph Waldo Gerard (1900–1974), studying nerve prop- [44] 65 14 erties with oscillography and including Joseph Erlanger 66 15 (1874–1965), Gasser, Bishop, Heinbecker and their fol- “The concept of the neurone as a nerve fibre provided 67 16 lowers. with a trophic centre and two specialized endings af- 68 17 fords satisfactory means of understanding the role of 69 [ ] 18 “ ... adequate demonstration of the character of neu- the intercellular connections within the nerves cen- 70 19 rone body potentials as such seems not to have been tres [...]” [47 (p. 608)] 71 20 reported, nor estimates of what fraction of the to- 72 21 tal potential observed was assignable to cells.” [45 Lorente de Nó explained facilitation and the reduc- 73 22 (p. 465)] tions in reflex latency by higher intensity stimuli by the 74 23 recruitment of more direct internuncial paths. Hence, 75 Hence, Eccles’ studies on ganglia were an attempt to 24 Eccles’ neuronal properties were seen among axonol- 76 experimentally establish concepts from the Cambridge 25 ogists as circuit properties and the specific role of indi- 77 school with the oscillographic approach of American 26 vidual neuronal somata was again dismissed. 78 27 axonology. The analysis remained speculative until a 79 consensus emerged from later studies on spinal cord. 28 10. Toward a consensus between American and 80 29 9. Polemics on the neurone in oscillographic slow British neurophysiologists 81 30 potentials recordings in spinal cord and 82 31 oculo-motor ganglia From our present standpoint, earlier conflicts be- 83 32 tween neurophysiologists, who fought to localize spe- 84 33 Once again, Gasser made the first step when he per- cific electrical properties either in the axon or the soma 85 34 formed localized measurements of slow potentials by of neurones, may seem strange. The elementary prop- 86 35 oscillographic recordings on the surface of the exposed erties of electrical membranes are currently thought to 87 36 spinal cord [46]. Gasser showed slow potentials were be rather homogeneously distributed over the neuronal 88 37 not occluded by initial antidromic stimulation, thought membrane, in spite of distinct distributions of specific 89 38 to establish a refractory period inside neuronal somata. ionic channels, receptors and some emergent electrical 90 39 Accordingly, he could not localize slow potentials in properties. However, physiological traditions favoured 91 40 motoneurones, but rather in secondary networks of in- dichotomy in localizing properties in anatomical ele- 92 41 ternuncial neurones, whose activity was interpreted as a ments. Neuronal properties emerged in Adrian’s analy- 93 42 slow shift of polarity within a dipolar equivalent circuit. sis from non-nervous properties. This approach can be 94 43 Gasser’s interpretation was dependent on Adrian’s con- regarded as a necessary step dividing and confronting 95 44 ceptions, but did not localize potentials precisely to spe- specific aspects of concepts in their genesis, before es- 96 45 cific neuronal elements. Furthermore,UNCORRECTED Gasser himself tablishing PROOF more sophisticated relations between them. 97 46 established a parallel between slow internuncial poten- Epistemological relations between somata, fibres and 98 47 tials and Sherrington’s central excitatory state. There- neuronal networks changed when Lorente de Nó and 99 48 fore, discussions on the c.e.s. focussed on whether it Eccles finally agreed, in the context of the polemic over 100 49 represented Eccles’ elementary neuronal slow potential electrical versus chemical neurotransmission. Both of 101 50 or Gasser’s and Lorente de Nó’s internuncial activity. them defended the electrical theory of neurotransmis- 102 51 Eccles did not pursue the question on Gasser’s exper- sion, which led Lorente de Nó to adopt a general view 103 52 imental ground, but further established his conceptions on nervous transmission based on the physiological in- 104 ARTICLE IN PRESS JID:CRASS3 AID:2439 /FLA [m3+; v 1.59; Prn:29/03/2006; 15:59] P.10 (1-13) 10 J.-G. Barbara / C. R. Biologies ••• (••••) •••–•••

1 dividuality of the neurone, with synaptic contacts con- activities, such as slow, often rhythmic potentials gener- 53 2 verging onto the neuronal soma. Hence, the neurone was ated by populations of neurones. Large-scale oscillat- 54 3 necessarily seen as a micro-circuit of its own. Conse- ing activities were interpreted as a synchronization of 55 4 quently, Lorente de Nó reworded his ideas according slow elementary neuronal activities. Adrian developed 56 5 to Eccles’ ones, which he felt closer than originally such an analysis on the isolated goldfish brainstem [49]. 57 6 thought. He made a clear parallel between his concept of But the question was already asked when Hans Berger 58 7 partially active internuncial circuit and the Cambridge (1873–1941) published slow potential waves recorded 59 8 school’s concepts of the motoneurone pool and the in- from the human scalp. Hallowell Davis’ (1896–1992) 60 9 active subliminal fringe. reaction to Berger’s discovery probably reflects the most 61 10 common attitude of physiologists, whether they adopted 62 11 “[...] using a term introduced by the Oxford school Davis’ or Adrian ’s view. 63 12 it may be said that during activity the internuncial 64 13 and motor pools become fractionated into active and “I explained patiently that it must be a vibration in 65 14 inactive groups, part of the latter group constituting his equipment or other artefact because it was un- 66 15 a subliminal fringe, the activation of which demands thinkable that enough axons in the brain could be so 67 16 stimulation of another set of pathways.” [48 (p. 212)] synchronized in their activity as to yield such slow 68 17 potentials.” [50 (p. 316)] 69 18 The early polemics on Sherrington’s c.e.s. led to this 70 19 new parallel between this concept and a theoretical state “It thus appears that the axons of the brain have much 71 20 of excitation in Lorente de Nó’s internuncial circuits. larger potential than elsewhere, or else the record is 72 21 due to nerve cells, having a higher and more pro- 73 22 “[...] the main difference between the concept of tracted potential than nerve fibers give.” [51] 74 23 c.e.s. used by the Oxford school and that of con- 75 24 tinuous stimulation by internuncial bombardment is The discovery of the Berger rhythm did not influence 76 25 that c.e.s. was assumed to develop and accumulate oscillographic studies during years 1932–1933. When 77 26 within the individual neurones, while internuncial Adrian discussed brain waves in his 1933 Nature article, 78 27 bombardment places the excitatory and facilitatory he mentioned Max Heinrich Fischer, Alois Eduard Ko- 79 28 mechanisms outside of the cell. For many theoretical rnmüller (1905–1968), Samuel Howard Bartley (1901– 80 29 arguments the difference may be overlooked; in fact, 1988), Bishop, but not Berger. Later on, Adrian partially 81 30 the result obtained is essentially the same, whether changed his view when he rejected the concept of c.e.s. 82 31 the one or the other concept is used.” [48 (p. 328)] in interpreting brain waves [52]. Nevertheless, a role of 83 32 slow neuronal elementary potentials remained central. 84 33 These convergent views were essential in the physi- 85 34 ological construction of the neurone concept, since neu- “The rate of beating will then depend on the con- 86 35 ronal somata were no longer rigid loci of convergence stitution of the cells and on nothing else. Thus the 87 36 and building of slow potentials, but also formed part of Berger rhythm is disappointingly constant, for it ex- 88 37 secondary neuronal circuits representing multiple sites presses time relations which are determined by the 89 38 of neuronal convergence, facilitation and subliminal ex- fundamental properties of the cells.” [53 (p. 382)] 90 39 citation involved in retroactive controls. These inter- 91 40 pretations finally led to a series of topographic elec- There was a crucial need for new concepts to han- 92 41 trophysiological studies on the functional organization dle assemblies of cortical neurones. Jasper was the first 93 42 of the spinal cord by Lloyd, Birdsey Renshaw (1911– American neurophysiologist to reproduce data on the 94 43 1948) and Eccles. These studies were based on isolated Berger rhythm. He dismissed Kornmüller’s attempt to 95 44 monosynaptic reflex arcs, thus avoiding internuncial ac- correlate brain rhythms with cytoarchitectonics and the 96 45 tivities, and permitting the preciseUNCORRECTED measurement of ele- temptation PROOF to return to interpretations based on closed 97 46 mentary neuronal parameters. chains of neurones. Close to Gasser, Jasper felt brain 98 47 rhythms should be analysed from knowledge of single 99 48 11. Berger rhythm (1929) and further questions on fibre activities, but he finally concluded: “it is of great 100 49 the neurone importance [...] to know what the single cortical cell is 101 50 doing.” [54 (p. 326)] Forbes’ initial microelectrode stud- 102 51 The physiological construction of the neurone was ies on cortex had revealed slow elementary all-or-none 103 52 based upon measurements of patterns of central nervous units possibly representing individual activities from 104 ARTICLE IN PRESS JID:CRASS3 AID:2439 /FLA [m3+; v 1.59; Prn:29/03/2006; 15:59] P.11 (1-13) J.-G. Barbara / C. R. Biologies ••• (••••) •••–••• 11

1 cortical somata [55–57]. In a 1948 review in Science, rowed extensively from the membrane physiology of the 53 2 Jasper [58] appealed for further studies of this kind. squid giant axon. Hence, intracellular recording allowed 54 3 However, Jasper’s 1952 Science review [59], summa- a more rigorous correlation of local potentials within 55 4 rizing recent microelectrode studies, showed that slow anatomically defined neuronal parts and allowed defi- 56 5 brain waves had no clear correlation with single neurone nition of numerical norms of neuronal activity, such as 57 6 activities. Elementary activities were either in phase or resting membrane potential, maximum action potential 58 7 out of phase or uncorrelated with brain rhythms. The depolarization and after-potentials. 59 8 only valid interpretation was that the Berger rhythm More importantly, the new intracellular paradigm al- 60 9 represented slow potentials in distal parts of neurones, lowed studies on the neurone to borrow concepts and 61 10 linked to chemical neurotransmission, but not to the all- techniques from the field of membrane physiology, with 62 11 or-none spiking activity of the neurone. Such an inter- the adoption of voltage-clamp, superfusion exchanges 63 12 pretation led to further studies on elementary dendritic of intracellular ionic contents and the modelling of ionic 64 13 potentials. A large symposium on dendrites organised permeabilities accounting for somatic and synaptic po- 65 14 by the American Society of Electroencephalographers tentials. Intracellular recording was much more than a 66 15 viewed dendrites as conductive and non-polarized el- technique that opened a new field of study. It was rather 67 16 ements, an opinion that many axonologists could not an important interdisciplinary locus for conceptual and 68 17 accept (1958). technical interactions. 69 18 Thus, in the context of building a neurone con- 70 19 cept based on localising slow potentials into cell parts, 13. Concluding remarks 71 20 the Berger rhythm came into play as a peculiar slow 72 21 and regular wave previously thought irreducible, with This inquiry into the physiological construction of 73 22 no single neurone activity, then theoretically accepted the neurone concept during the early 20th century hints 74 23 as a synchronisation of simple all-or-nothing neuronal at how epistemological conflicts emerge from con- 75 24 potentials, before this hypothesis was finally rejected. frontations between disciplines. Comparison of national 76 25 However, the resulting polemic was profitable for the contexts shows how boundaries between disciplines, 77 26 definition of the neurone, further distinguished from its conflicts and convergences permitted the emergence of 78 27 axonal activity and with dendrites that emerged as inde- a specific concept. Different evolutions in adopting, re- 79 28 pendent conductive elements. jecting, or developing the neurone concept depended on 80 29 complex relations between anatomy and physiology in 81 30 12. The view from inside different nations. 82 31 The interdisciplinary construction of the neurone 83 32 Extracellular studies on the neurone took advantage was dependent on personal backgrounds, social rela- 84 33 of monosynaptic reflexes and dissociated single neu- tions between researchers of neighbouring disciplines. 85 34 rones [60–62], but still divergences emerged in the lo- In this context, the legitimacy of histological and phys- 86 35 calization of specific potentials to distinct cell parts, iological revisions of the neurone concept changed as 87 36 as illustrated by the polemics between Lloyd and Ec- new approaches and techniques were developed. The 88 37 cles (1949–1951) and differing ideas on dendritic con- early proposal of the neurone concept allowed histol- 89 38 duction. The first intracellular records were made from ogy to extend its functional implications from anatom- 90 39 muscle cells and giant nervous fibres by Alan Lloyd ical observations, which confronted physiological data 91 40 Hodgkin (1914–1998), Kenneth Stewart Cole (1900– on the polarization of nervous conduction. Sherrington 92 41 1984), Howard James Curtis (1906–1972) and Gerard. borrowed from the notions of Ramón y Cajal to base his 93 42 Eccles records from cat motoneurones opened a new studies on the neurone concept. With his work, physiol- 94 43 field of membrane and action potential studies on neu- ogy overcame histology in its legitimacy to rectify and 95 44 rones in close conjunction with the complex frame- build the neurone concept as physiological. In France, 96 45 work of extracellular studies. InvadingUNCORRECTED backpropagat- Lapicque PROOF did not find any legitimacy with the theory of 97 46 ing action potentials recorded inside the soma was a chronaxie as speculative as his opponents’ histophysio- 98 47 direct proof of the old idea that spikes could spread logical theories. 99 48 from the axon to the soma, a view later extended to Physiological interest in the neurone concept emerged 100 49 dendritic backpropagation. Synaptic potentials replaced in two British schools that combined in the studies of 101 50 Sherrington’s c.e.s. and end-plate noise [63]. Eccles’ Adrian. New instruments and measurements of single- 102 51 1952 concept of the neurone [64] was a synthetic view fibre activities in Sherrington’s reflexology led to a new 103 52 that combined extracellular neurophysiology and bor- and direct objectivation of the neurone concept by con- 104 ARTICLE IN PRESS JID:CRASS3 AID:2439 /FLA [m3+; v 1.59; Prn:29/03/2006; 15:59] P.12 (1-13) 12 J.-G. Barbara / C. R. 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