Charles Scott Sherrington and T He Integrative Action of The

醫史學 제10권 제1호(통권 제18호) 2001년 6월 Korean J Med Hist 10∶ 1– 22 June 2001 大韓醫史學會 ISSN 1225– 505X

D e v e lopme nt of ne urophy s iolog y in the e arly tw e ntie th c e ntury : Charle s S c ott S he rring ton and T he Int e g rat iv e A c t ion of t he N e rv ous S y s t e m

Ock- Joo Kim*

In the late nineteenth and early twentieth writings on neuroscience Sherrington wrote centuries Charles Scott Sherrington made an philosophical and historical works such as Man indelible contribution to the history of on His Nature (1941) and The Endeavour of neurophysiology While studying the vast field Jean Fernel (1946) which showed his diverse of neurophysiology for more than a half of interests and talents The scope of Sherrington s century he resolved many problems which had contributions marks him as a major figure in the hindered the progress of neurophysiology Based history of neuroscience However the greater upon his extensive experimental work he significance of his work lies in his synthetic generalized his observations producing concepts attitude his perception of the interrelatedness terms and principles that became the basis of of his varied researches Like the title of his modern neurophysiology In his work The book he integrated the work of himself and his Integrative Action of the Nervous System (1906) predecessors and colleagues into the foundations Sherrington not only presented important concepts of modern neurophysiology such as proprioception reciprocal innervation motoneuron synapse and final common path The Life of Charles Scott Sherrington but also inspired researchers to look at the living animal as sustaining its integrity through various Sherrington was born on November 27 1857 actions of the nervous system In addition to his while his parents were visiting Islington London 1)

* Department of the Medical History and Medical Humanities Seoul National University College of Medicine 1) For a short description of Sherrington s life and scientific activities see Judith P Swazey Charles Scott

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When Sherrington was very young James chance to do histological studies with monkey s Norton Sherrington died and his mother Anne medulla and dog s spine This first neurological Brookes later married Dr Caleb Rose, Jr to research aroused his interest in neurophysiology whom Sherrington became much devoted imparting to him Langley s dominant interest in Sherrington s broad interests as scientist how anatomical structure reflects or is expressed philosopher and poet originated during his in physiological function childhood in his step-father s house at Ipswich From 1884 to 1887 Sherrington completed his The Rose home a gathering place for artists and medical courses and pursued graduate study in scholars helped to shape Sherrington s broad clinical medicine as well as in laboratory interests in science philosophy history and sciences in England and Europe These years poetry From 1870 to 1875 he attended Ipswich were fascinating to Sherrington providing him Grammar School where he learned classics with superb scientific training under many leaders languages history and literature In June 1875 of late nineteenth-century biological sciences In at the age of eighteen Sherrington passed the the early part of the year 1884 he continued his Preliminary Examinations in General Education clinical studies at St Thomas hospital where he of the Royal College of Surgeons although it experienced startling and ineffaceable was unusual for a student to pass medical out-patient work examinations before studying at Cambridge or When he won the George Henry Lewes Edinburgh In September 1876 he began Studentship for Physiological Research in 1884 medical training at St Thomas Hospital in Sherrington stopped clinical work and went to London the continent to study At Foster s suggestion In 1879 Sherrington was admitted to Caius he went first to Bonn to study under Edward College Cambridge where he studied and in Pflüger (1829-1910) but spent only one or two 1883-1884 served as a demonstrator in anatomy months there Then he traveled to Strasbourg to and histology to Sir George Humphrey but he work in Friedrich Goltz s laboratory where worked chiefly under John Newport Langley and every condition was designed to foster research Walter Gaskell in Sir Michael Foster s rather than instruction As a research topic Goltz physiological laboratory After taking an arts assigned the young Englishman the microscopic degree in 1884 Sherrington continued doing study of secondary and tertiary nerve fiber and research under Langley who offered him a tract degeneration which turned out to be very

Sherrington Dictionary of Scientific Biography pp 395-403 John F Fulton Charles Scott Sherrington O M Experimental Neurology Viol 2 (Feb 1960) idem Sir Charles Scott Sherrington O M Journal of Neurophysiology 15 167-190 (1952) Swazey deals with his life and his work on the nervous system in detail in her book Reflex and Motor Integration Sherrington s Concept of Integrative Action (Harvard University Press Cambridge Massachusetts 1969)

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profitable The study of nerve degeneration continued his pathological studies In Berlin he interested Sherrington deeply in the relationship became acquainted with many leading of structure to function in the central nervous contemporary scientists such as Hermann von system and in 1885 resulted in his first Helmholtz Emil Du Bois Reymond and independent paper from the laboratory 2) Wilhelm Waldeyer In the summer of 1885 after finishing his On his return from Berlin in 1887 training with Goltz Sherrington left for Spain Sherrington was elected a Fellow of Caius with Charles S Roy and J Graham Brown to College and appointed a lecturer in systematic investigate an outbreak of Asiatic cholera in physiology at St Thomas s Early in 1888 Spain on behalf of the Association for Research Sherrington became engaged to marry Ethel in Medicine and the Royal Society They Wright of Preston Manor England Three years successfully demonstrated the causative bacteria later with the improvement of his financial in the feces and nasal mucous membranes of situation resulting from his appointment as fatal cases The following year Sherrington Physician-Superintendent of the Brown Institution went to Italy to investigate an cholera outbreak a London animal hospital in 1891 they married spending one or two months in Venetia Puglia and lived in London at 27 St George s Square and Venice until they moved to Liverpool in 1895 Their Having developed an enthusiasm for pathology only son Carr E R Sherrington was born in Sherrington journeyed from Italy to Rudolph 1898 While he served as Virchow s laboratory in Berlin to study his Physician-Superintendent of the Brown Institution cholera specimens It was not until after his Sherrington conducted various researches taking arrival that he realized that Virchow devoted full advantage of the supply of animals for himself to science much less spending most of experimentation Although after returning from his time in politics as an opponent of Bismarck Berlin he had decided to devote himself to After two months Sherrington left Virchow s neurophysiology rather than pathological study laboratory dissatisfied with the facilities and he continued to work on diverse subjects in opportunities With a letter of recommendation pathology and general physiology On October from Virchow written after he examined 15 1894 he became the first man in England Sherrington s cholera tissue Sherrington entered to use antidiphtheritic serum for therapeutic Robert Koch s Berlin laboratory for a year s work purposes when he saved his brother-in-law s At Koch s laboratory Sherrington took a only son George who was eight years old six-week required course in bacteriological from the last stages of diphtheria In his later technique valuable training for him and years of the Brown Institution Sherrington

2) Charles S Sherrington On secondary and tertiary degenerations in the spinal cord of the dog Journal of Physiology 6 (1885) pp 177-191

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began to focus his attention on spinal cord living in a workman s hut and working twelve functions hours a day for eleven weeks Returning to From 1895 to 1912 Sherrington held the Holt Oxford he reported to the War Office that professorship of physiology at Liverpool He also war-factory laborers would accomplish more with took an active role in scientific organizations shorter working hours and more adequate living From 1889 through 1905 he served as Honorary conditions Secretary of the Physiological Society and As soon as the war ended Sherrington concurrently from 1892 to 1907 as a general resumed his ordinary teaching and research secretary of the International Physiological program He was a gifted teacher as well as an Congress demonstrating his special ability for excellent researcher In 1919 Sherrington organization and administration While at published Mammalian Physiology A Course of Liverpool he continued to be intensely Practical Exercises a book which reflected his productive in his research developing new belief in students active participation in their techniques and accumulating great amount of own physiological education In his last years at research material One of the highest points of Oxford Sherrington received two major honors his academic activities came in 1904 when he At the First International Neurological Congress was invited to be Yale University s second held at Berlin in August 1931 he received an Silliman Lecturer The lectures published in honorary degree along with Harvey Cushing and 1906 as The Integrative Action of the Nervous in 1932 the Nobel Prize in Physiology and System were acclaimed as a turning point in the Medicine At the Berlin Congress Professor history of neurophysiology because of their Leon Asher awarding the degree to Sherrington originality philosophical insight and intellectual ended with the following remarks Sir Charles stimulus for further research we look upon you as the supreme philosopher of On coming to Oxford in 1913 as the the nervous system 3) Huge applause from the Wayneflete professor of physiology Sherrington audience followed found a large department with ninety students In 1935 Sherrington decided to retire from But the outbreak of the First World War in the Wayneflete Chair at the age of seventy-eight August 1914 left him with only seven students although at this time Oxford had no compulsory who were physically unfit for military service retirement age Returning to Ipswich for his Sherrington was also asked by the War Office to retirement years he served the community as an study industrial fatigue in the war plants In advisor on the town s museum and health order to get first-hand information he entered services and as an Ipswich School Governor the Vickers-Maxim shell factory in Birmingham But his major concern was to work as

3) Judith P Swazey Reflex and Motor Integration Sherrington s Concept of Integrative Action p 26

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philosopher and historian centering the issue on and their interrelationships in producing reflexes the mind-body relationship Like Descartes To correlate the various separate channels of Sherrington held dualism not because of research a solid foundation of neuroanatomical philosophical choice but because of the knowledge was necessary non-existence of scientific means to bridge the In 1884-85 Sherrington first explored gap between mind and body in his day In 1940 neurophysiology with preparation supplied by he published Man on His Nature which he Goltz at Strasbourg This study the first paper delivered as Gifford Lectures on philosophical published under his own name dealt with the topics for 1937-38 at Edinburgh University experimental determination of what part of the Until 1939 he stayed in Ipswich and then as cortex caused the degeneration of the pyramidal his health failed moved to Cambridge He tracts if injured 4) The second paper of 1889 also remained intellectually alert receiving a constant treated the cortex and pyramidal tracts It stream of visitors and continued his writing On marked a turning point in his scientific career the evening of March 4 1952 he died He began to operate on dogs and monkeys rather peacefully from heart failure in his ninety-fifth than use preparations provided by others 5) In year 1889 he came to realize that his research had begun at the wrong end for the relationship of The first step for the life - long the cortex to pyramidal tract degeneration was research Neuroanatomical studies too complex for him to elucidate Influenced largely by Gaskell Sherrington began to Sherrington s life-long work dealt primarily investigate the spinal cord which provided a with the functional anatomy of the nervous much simpler structure for study and turned out system and reflex motor behavior in vertebrates to be fruitful When he began to study neurophysiology in In his study of the spinal cord Sherrington 1887 huge amounts of data had been began with the investigation of the nature of the accumulated but in almost all areas of knee jerk Since C I O Westphal and W H neurophysiology there were controversies and Erb had described the knee jerk clinically in few attempts had been made to correlate 1875 debate surrounded the nature of knee jerk structural with functional data For example While Erb contended that knee jerk was a true studies of reflex action had continued without tendon reflex involving neural conduction to the correlation of such studies with the anatomical cord and back Westphal asserted that the knee structure of nerve cells spinal cord and brain jerk was a direct mechanical twitch of the

4) Charles S Sherrington 1885 5) Charles S Sherrington On nerve-tract degenerating secondarily to lesions of the cortex cerebri Journal of Physiology 10 1889 pp 429-432

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muscle which needed a state of tonus as a In his studies on the distribution of the motor necessary condition for its occurrence When he nerve roots Sherrington used chiefly the entered the debate Sherrington thought that lumbo-sacral roots of Macacus rhesus and also anatomical understanding of the reflex was those of rat rabbit cat dog mainly for the necessary because Erb and Westphal had argued sake of comparing those types with Macacus without detailed studies on the anatomical basis After anesthetizing them with chloroform and of the reflex Thus Sherrington s first study of ether he excited spinal roots in the spinal canal the phenomenon of the knee jerk was on the or a single root or a component filament nerves and muscles upon which the action isolated from lower roots of the cat and monkey 10) depended 6) He found out that he could not deal What he discovered was that a muscle and its satisfactorily with the functional problems without motoneurones in the grey matter of the spinal sufficient neuroanatomical knowledge of the cord formed the true functional unit and in the distribution of the sensory and motor fibers of limbs the original anatomical segmentation the spinal cord became less distinct as one passed from For the next decade he investigated the nerve-roots distally Each of the muscles of the nature of motor and sensory innervation limb the functional elements of the physiological including the field of distribution of each spinal machine was compounded and pieced together root and thereby created the anatomical out of myotomes or segments Therefore most foundation necessary for physiological work His muscles were multiply innervated and could be three major contributions to neuroanatomy in this stimulated from different levels of the spinal cord period were (1) mapping motor pathways When he studied the distribution of the chiefly in the lumbosacral plexus7) (2) tracing sensory nerve roots Sherrington recognized that the cutaneous distribution of the posterior spinal observations on the distribution of sensory nerve root8) and (3) establishing the existence of roots were more difficult than those of motor sensory nerves in muscles 9) nerve roots Whereas stimulation to motor roots

6) Charles S Sherrington Note on knee-jerk St Thomas Hospital Reports 21 (1891) pp 145-147 Note toward the localization of the knee-jerk British Medical Journal 1 (1892) 545 Addendum Ibid p 654 7) Charles S Sherrington Notes on arrangement of some motor fibres in the limbo-sacral plexus Journal of Physiology 13 1892, pp 612-772 8) Charles S Sherrington Experiments in examination of the peripheral distribution of the fibres of the posterior roots of some spinal nerves (I) Philosophical Transactions 184B 1894 pp 641-763 idem Experiments in examination of the peripheral distribution of the fibres of the posterior roots of some spinal nerves (II) Philosophical Transactions 190B 1894 pp 45-186 9) Charles S Sherrington On the anatomical constitution of nerves of skeletal muscle with remarks on recurrent fibres in the ventral spinal nerve-root Journal of Physiology 17 1894 pp 211-258 10) Charles S Sherrington Notes in the arrangement of some motor fibres in the lumbosacral plexus Journal of Physiology 13 1892 p 635

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resulted in muscular contraction excitation of the motor supply of the underlying muscle In the central end of a nerve trunk containing the skin of Macacus the pain field and the afferent nerve fibers initiated reflex actions of heat field of a single sensory spinal root were various kinds and degrees Moreover the each less extensive than was the touch field of experimenter could not get results directly from the same root In the heat fields and pain the animal by asking it about sensations which fields of the roots the extent of overlap was subject might experience from the stimulation of greater in some skin region than in others for afferent trunks or roots As criteria of the example in the hand and foot greater than in existence of afferent nerve fibers Sherrington parts of the forearm thigh and trunk Based chose arterial pressure and respiratory reflexes upon the observations on distributions of both and explored spinal connections of the afferent sensory and motor nerve roots Sherrington nerve trunks of lower limb in anesthetized concluded that the formation of functional animals By severance of the afferent rootlets of collections of nerve fibers (peripheral nerve the spinal nerves by which a peripheral nerve trunks) out of morphological collections (nerve trunk was connected with the cord the reflex roots) … is the explanation - the meaning - of originated through it could be diminished or set the existence of nerve plexuses 12) aside completely 11) If the peripheral trunk Sherrington s one of the most important communicated with the cord through the channel contributions to neuroanatomy in this period was of several roots the reflex would diminish his clear demonstration of the sensory nerves to There would be no reflex if the severance muscles Charles Bell was the first to postulate included all the lines of the connection From the existence of special afferent peripheral nerves these experiments Sherrington discovered that for impulses evoked by the movement and each afferent spinal root contributed to several posture of the body In 1894 Sherrington nerve trunks and thus produced overlapping of demonstrated that large numbers of nerve fibers skin fields and that each afferent spinal root in the muscular nerves had the dorsal root had a continuous and self-contained segmental (afferent) origin 13) The afferent nerve fibers skin field Contrary to Krause and other scholars distributed in a given muscle arose in the root opinion the segmental sensory supply of an area ganglia of exactly those spinal segments whence of skin was shown to be different greatly from emerged the motor fibers for the same muscle

11) Charles S Sherrington Experiments in examination of the peripheral distribution of the fibres of the posterior roots of some spinal nerves (I) Philosophical Transactions 184B 1894 pp 654 12) Charles S Sherrington Experiments in examination of the peripheral distribution of the fibres of the posterior roots of some spinal nerves (II) Philosophical Transactions 190B 1898 p 152 13) Charles S Sherrington Experiments in examination of the peripheral distribution of the fibres of the posterior roots of some spinal nerves (I) Philosophical Transactions 184B 1894 pp 641-763

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Sherrington found the afferent fibers both in and as an adaptive reaction The purpose and effect from muscles and showed muscles to possess of reflexes of the organism were to enable the sense organs functioning independently of the organism to adapt to its environment Thus overlying skin He also proved the sensory the reflex reaction cannot be really intelligible nature of the spindles by the degeneration of its to the physiologist until he knows the purpose 15) nerve fibers Muscle spindles lied numerously The degree of the evolution of the nervous imbedded in the muscular tissue and were system which was the seat of reflex action especially abundant in the vicinity of aponeuroses showed most apparently how much the organism tendinous intersections and tendons According could dominate the environment The more to Sherrington it was shown above that about various and extensive the responses made by the two-thirds of all the afferent fibers measure organism through more elaborated reflex system above 7 diameter Of these I imagine that the more completely the organism could considerably more than a half may be understand the complexity of the world around apportioned to the muscle spindle the majority While Sherrington acknowledged that the study of the rest belonging probably to Golgi s of behavior could illuminate the purpose of tendon-organs 14) The discovery of the existence total reactions of the organism in its environment of sensory nerve fibers in the nerves and their he confined his study of adaptive nature of end organs enabled Sherrington to understand the reflexes into more simpler one Analyzing the reflex nature of posture and tonus in his later animal s life as a machine in action studies Sherrington broke down its total behavior into Sherrington s publications from 1884 through fractional parts which were reflexes and 1898 running to about 700 pages in total attempted to understand immediate purpose of illustrated that he had opened new paths to each reflex as an adapted act Reflexes could be anatomical and physiological knowledge of the explained to have either of a preservative nervous system Concomitant with his anatomical character or the movement which the functions work and often deriving from it was a of the organ required profusion of ideas and observations on the reflex In the his study of reflex activity Sherrington function of the spinal cord used a basic method of studying simple motor acts which could be made to occur in isolation The spinal animal and spinal reflex activity correlating his exacting analysis of input-output relations of reflex responses with anatomical and Sherrington approached the reflex phenomena histological data To study simple acts of muscle

14) Charles S Sherrington On the anatomical constitution of nerves of muscles Journal of Physiology 17 1894-95 p 247 15) Charles S Sherrington The Integrative Action of the Nervous System 1947 edition p 237

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management at the spinal level in living animals inhibition phenomena due to the irritation of the Sherrington eliminated the higher controlling trauma Sherrington thought that the phenomena regions of the brain and brain stem He reduced was caused by the cutting off by the trauma of his experimental animal to a functioning isolated some supra-spinal influence In the Marshall Hall spinal cord or cord segment capable of Lecture in 1899 Sherrington presented some executing limb reflexes in response to given reasoning and evidences 18) First the spinal stimuli Sherrington called the experimental shock took effect almost exclusively in the aboral animal puppet animal in which the mindless direction Second Sherrington performed body reacts with the fatality of a multiple experiments in which he transected the spinal penny-in-the slot-machine to certain [physical] cord at eighth cervical level and again a couple stimuli … A point is that these mindless acts yet of segment after original transection and treat the animal s motor machinery as a united checked the changes of vascular reflex The first whole Thus the mindless machine can walk trauma caused temporary deep depression of and run and gallop it can also spring … There spinal tonus of the vascular system and is integration although purely motor integration temporary abolition of vascular reflexes while 16) Sherrington s puppets were of two types the second trauma caused no depression The the classic spinal animal whose cord has been shock following the trauma was proportional not permanently transected above the lumbosacral to severity of the wound but to the number and enlargement and the decerebrate animal character of the descending nerve paths through Decerebration was done by actual removal of the which the lesion broke To Sherrington the cerebrum or by transection of the brain stem an condition of the spinal reflex-arcs in spinal shock old technique appeared to resemble a general spinal fatigue Whenever he prepared the spinal animal rather than an inhibition The origin of spinal Sherrington observed spinal shock which had shock seemed to be right behind pons not in been difficult in deciphering the purpose of cerebrum for the ablation of the hemisphere did reflexes The definition of spinal shock was not induce such a degree of the spinal depression made by Marshall Hall If in a frog the spinal as that induced by transection behind the pons marrow be divided just behind the occiput there He also found that all reflex did not suffer from are for a very short time no diastalic actions in the spinal shock with equal severity Various the extremities The diastalic actions speedily spinal reflexes recovered within various times returns This phenomenon is shock 17) While During his research on the reflexes with the Goltz considered it entirely a collection of spinal animal he found that the location of the

16) Ibid., Forward p xii 17) Marshall Hall Synopsis of the Diastalic Nervous System London 1850 18) Charles S Sherrington On the spinal animal Medical-Chirugical Transactions 82 1899 pp 449-44

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stimulus played important role in determining the of motor control He also presented the concepts nature of the reflex evoked This influence of of muscular sense inhibition and facilitation as the location of the stimulus on the resulting the three key mechanisms of muscle management reflex movement provided some direct evidences at the spinal level The next stage of his work of the purposive character of spinal reflexes was to determine how reflex arcs combine to The afferent impulse involved could be divided form successively larger and more complex reflex into three according to their place of origin (1) patterns In 1904 before the Physiological a group originated at the seat of stimulus (2) a Section of the British Association for the group initiated in the motor and mobile organs Advancement of Science Sherrington delivered a reflexively set in action (3) in some cases a lecture The Correlation of Reflexes and the group arising at the distant spot to which the Principle of the Common Path His main theme was the reflex chain of the synaptic system the movement was directed In the execution of receptive neuron formed a private path into the these spinal reflexes the most important afferent brain or cord within the central nervous system factor as regards local sign was the afferent many private paths converged at an internuncial channel from the place of initiation of the reflex neuron to form a public common path which ran While Sherrington studied on the nature of to a motor neuron from the motor neuron spinal reflex activity he focused on two major impulses traveled over a final common path to researches One was analyses of antagonistic converge upon the effector organ muscle action and the other was those of complex reflexes such as the extension flexion The Integrative Action of the Nervous and scratch reflexes of the hind limb While he System studied these subjects Sherrington reached the conclusion that main secret of nervous co-ordination In 1904 Sherrington synthesized what he had … lies in the compounding of reflexes 19) This studied about neuro-physiology for twenty years process involved necessary processes of excitation and had a chance to present it in front of and inhibition at the synapse the intercellular neurologists and neurophysiologists in America connection His studies on reciprocal innervation In April 1904 invited as the second Silliman of antagonistic muscles are found in his fourteen Lecturer at Yale University Sherrington gave ten classic Notes in the Proceedings of the Royal lectures on Integrative Action by the Nervous Society from 1903 to 1909 System It was published in 1906 under the By 1900 Sherrington had developed two of title The Integrative Action of the Nervous basic functional principles reciprocal innervation System At its fifth reprinting the book was and interaction between higher and lower centers appraised by F M R Walsh it holds a

19) Charles S Sherrington The Integrative Action of the Nervous System 1947 edition p 8

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position similar to that of Newton s Principia in contained important discoveries as well as physics In this book Sherrington synthesized principles Sherrington s three central his own experimental studies with other prepositions for nervous integrative action were researchers and presented generalized ideas and (1) that the nervous system was one if not the principles of the neurophysiology Between two only major integrative agent in complex kinds of actions of the nervous system motor multicellular organisms (2) that the reflex was and visceral this book aimed primarily to the unit reaction in nervous interaction (3) that illuminate the behavior of the motor reflex and there were two grades of reflex coordination did not deal with excretory action of the nervous namely that effected by the simple reflex and system Sherrington chose the reflex in motor that effected by the simultaneous and the behavior as his subject because of the advantages successive combination of reflexes arising from the nature of the reflex it could be Sherrington devoted the first one-thirds of The studied free from complication with the psyche Integrative Action of the Nervous System to the also free from complication with that type of exposition about operation of the reflex arc the nerve activity called autochthonous that generated unit mechanism of the integrative nervous action intrinsically rhythmic movements e g According to Sherrington the unit reaction in breathing nervous integration is the reflex because every The ten chapters of The Integrative Action of reflex is an integrative reaction and no nervous the Nervous System can be divided into six parts action short of a reflex is a complete act of (1) Sherrington s definition of his topics in the integration 20) The reflex activity involved the first seven and a half pages of lecture I (2) three processes initiation conduction and Lectures I-III coordination in the simple reflex end-effect To each process three separate (3) Lectures IV-VI coordination between structures - the receptor conductor and effector - reflexes - their interaction and compounding by corresponded The first part of the reflex the simultaneous and successive combination (4) receptor determined the characteristics of the Lecture VII reflex as adapted reactions (5) organism s reaction to the environment for the Lectures VIII to IX the brain s role in receptors were the interface between the integrative motor action (6) Lecture X sensual organism and environment Function of the fusion As the contents show the book begins receptor was to lower for its reflex arc the from basic definitions and simple reflexes and threshold value of one kind of stimulus and to moves to more complex subjects heighten the threshold value of all other kinds of Based upon ample experimental data The stimuli for that arc Thus each reflex arc had Integrative Action of the Nervous System evolved to respond to one specific kind of

20) Ibid p 7

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stimulus and that was adequate stimulus This application of stimulus and appearance of selective excitability of the arc conferred by end-effect this difference being greater for weak receptors contributed to the reflex coordination in stimuli than for strong (2) less close two ways On the one hand it increased the correspondence between the moment of cessation responsiveness to environment by making an arc of stimulus and the moment of cessation of receptive to certain kinds of stimuli kinds to end-effect i e there is a marked which other arcs were less responsive On the after-discharge (3) less close correspondence other hand by limiting particular stimuli to between rhythm of stimulus and rhythm of particular body reaction the receptors helped to end-effect (4) less close correspondence between prevent confusion of reactions (inco-ordination) 21) grading of intensity of the stimulus and the In Sherrington s laboratories electrical stimuli grading of intensity of the end-effect (5) were commonly used Although they were not considerable resistance to passage of a single adequate stimuli the intensity and duration of nerve impulses but a resistance easily forced by the stimulation could be easily controlled with a succession of impulses (temporal summation) the electrical stimuli (6) irreversibility of direction instead of The conduction mechanism in reflex arc reversibility as in nervous trunks (7) fatigability played an essential role in coordinating reflexes in contrast with the comparative infatigability of and thus in integrating the nervous action nerve-trunks (8) much greater variability of the Sherrington s one of the most important threshold value of stimulus than in nerve-trunks contributions was the illumination of the (9) refractory period bahnung inhibition and characteristics of the synaptic reflex arc shock in degrees unknown for nerve-trunks conduction Before Sherrington nerve (10) much greater dependence on blood conduction had been studied chiefly in circulation oxygen (11) much greater nerve-trunk Although in large part conduction susceptibility to various drugs-anesthetics 23) in reflexes was conduction along nerve trunk Sherrington recognized that these differences yet reflex conduction in toto differ widely from were largely due to the intercalation of synaptic nerve-trunk conduction 22) Utilizing data since membranes in the conductive mechanisms of the the time of Robert Whytt and his own arc that was intercellular barriers made of Sherrington analyzed the major characteristics delicate transverse membrane He thought that distinguishing reflex arc from nerve trunk the nerve impulse was a physical process rather conduction as following (1) slower speed as than a chemical one If it was a physical measured by the latent period between process the intercalation of a transverse surface

21) Ibid p 13 22) Ibid 23) Ibid p 13-14

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of separation or membrane into the conductor after-discharge upon the production and must modify the conduction and the observation maintenance of a reflex response in contrast to of the reflex arc conduction and nerve-trunk conduction along nerve-trunks he figuratively conduction showed such differences describe them as inertia and momentum of After distinguishing reflex arc conduction from reflex arc reactions Using a simple analogy nerve trunk conduction Sherrington discussed from mechanics he suggested that it is as four phenomena in relation to the characteristics though in the case of a weight to be pulled from of reflex arc based upon his bulk observations a position of rest the tractive force were applied latency after-discharge summation and through a rigid rod in nervous trunk conduction refractory period Latency was the interval but through a relatively yielding elastic band in between application of stimulus and appearance reflex arc conduction 24) of end-effect While in nerve trunk there was In the second chapter Sherrington explored no measurable delay or latent interval reflex further the characteristics of reflex conduction conduction showed longer latency For example summation and refractory period Reflex-arcs a reflex conduction took double time of nervous showed high capacity of summing excitations conduction Reflex latency was inversely Reflex arcs summated subliminal stimuli so that proportional to the intensity of stimulation With by repetition they became effective and this was intenser stimuli the latent period of this reflex practically unknown in nerve-trunk conduction became much less Conduction speed was the Refractory phase was prominent in reflex arc same in various cerebrospinal nerve trunks of the conduction Even in nerve-trunk conduction a same animal species In nervous trunk the refractory phase must occur Otherwise the latency was proportional to the interval of the conductor being capable of reversible direction a distance between the two points But reflex backward propagation of the excited state as well conduction speed as measured by latent period as a forward would ensue from every point of differed greatly in various type-reflexes of even the conductor reached the nervous impulse The one and the same limb After-discharge the excited state would then when once excited period between stimuli cessation and response maintained itself in a tetanic manner along the cessation was a characteristic of reflex reactions whole length of the conductor While this After-discharge was increased by the refractory phase in nerve-fibers was very brief intensification of the stimulus or by prolongation no longer than 1 second that of reflex arc was of short stimuli The after-discharge could longer An essential part of many reflexes was a however be cut short sharply by inhibition more or less prolonged refractory phase Considering the effects of latency and succeeding nervous discharge Sherrington

24) Ibid p 34

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thought that the refractory phase of the scratch simultaneous double sign Sherrington drew the reflex had intraspinal seat and refractory phase concept of reciprocal inhibition The end effect was a factor of fundamental importance in of this kind of reflex was expressed by two coordination of certain motile action Variation groups of muscle whose contractions acted in of the external stimulus had comparatively little opposed direction at the same joints Reflexes effect upon the length of the refractory period with reciprocal inhibition had excitatory state as But internal condition such as fatigue narcosis regards to the motor nerve to the flex muscle blood supply influenced it greatly The duration but suppression or withholding of excitatory state of the refractory period varied considerably in (central inhibition) as regards to the motor different types of these reflexes neuron of the extensor This particular After explaining characteristics of reflex arc correlation in which one muscle of an conduction Sherrington discussed double sign antagonistic couple was relaxed as its mechanical reflexes which concluded his analysis of simple opponent actively contracts allowed movements reflex coordination and paved the way for such as flexion and extension of limb to be discussion of the coordination between reflexes harmoniously coordinated As for mode of He designated excitation as end-effect by the operation of reciprocal inhibition Sherrington sign plus (+) and inhibition as end-effect by showed that the process must be viewed as an sign minus (-) Then he classified reflex active and central one Like refractory period interactions into two a reflexes of successive the reciprocal inhibition could be induced by double-sign and reflexes of simultaneous double stimulating isolated spinal cord or by higher sign levels such as pyramidal fibers A reflex of successive double-sign developed excitatory end-effect and then inhibitory The next step that Sherrington took after end-effect even during the duration of the discussing the simple reflex was to examine exciting stimulus Scratch reflex was one of the compounding of reflexes and their interaction them Reflexes of simultaneous double sign were He examined the simple reflex because of its reflexes in which the end-effect consisted both in convenience for analysis But he knew that excitatory state and in inhibitory state But the simple reflex was an artificial abstraction and a inhibitory state did not supervene on excitatory main problem in nervous co-ordination was or have the same locus of incidence as the compounding of reflexes To discuss the nature excitatory It occurred simultaneously with of reflex interaction he introduced the principle excitatory at another interrelated locus For of the common path example the ordinary flexion-reflex of the hind Sherrington called the terminal path in the limb of the spinal cat or dog was one of the reflex arc the final common path The reflex of simultaneous double sign motor-nerve to a muscle was a collection of final From the discussion of the reflex of common paths A single receptive point might

－ 14 － Ock-Joo Kim∶ Development of neurophysiology in the early twentieth century

play as a stimulus upon quite a number of be a problem of frequent recurrence in reflex different effector organs Yet all its reflex-arcs co-ordination We see one act succeed another sprang from the one single stem (afferent neuron) without confusion … but for an array of which conducted from the receptive point At environmental agents acting concurrently on the the termination of every reflex arc there was a animal at any moment to exhibit correlative final neuron the ultimate conductive link to an change in regard to it so that one or other effector organ (muscle or gland) It did not group of them becomes … generally by increase subserve exclusively impulses generated at one in intensity … temporarily prepotent Thus there single receptive source but received impulses dominates now this group now that group in from many receptive sources situated in many turn 26) and various regions of the body It was the sole path which all impulses no matter whence they Sherrington classified the mode of interaction came must travel if they were to act on the between reflexes into allied reflexes and muscle fibres to which it led Therefore while antagonistic reflexes Allied reflexes acted the receptive neurons formed a private path harmoniously were capable of simultaneous exclusively serving impulses from one source combination and in many cases reinforced one only the final or efferent neurone was a public another s action on the final common path For path common to impulses arising at any of example type-reflexes such as scratch reflex many sources of reception 25) flexion-reflex of the hind limb extensor-thrust Owing to this architectural arrangement were group reflexes The individual reflexes afferent arcs which used the same final common comprised in each of these type-reflexes had path to different effect had successive but not such mutual relationship between themselves that simultaneous use of it There was no they acted harmoniously together on the same compromise between two reflexes and no final common path and were therefore allied algebraical summation of the influence exerted on reflexes Inhibitory reflexes were also allied the final common path by two opposite receptive For example several reflexes combined arcs In terms of adaptation to environment harmoniously together in exerting a conjoint Sherrington explained how the final reactions inhibitory influence on the knee reflexors were determined when there were various Another important example of allied reflexes receptive inputs was alliance of proprio-ceptive with extero-ceptive reflexes Proprio-ceptive reflexes The dilemma between reflexes would seem to were reflexes which had receptors specific to

25) Ibid p 117 26) Ibid p 120

－ 15 －醫史學 제10권 제1호(통권 제18호) 2001년 6월

themselves The receptors were consonant with reflexes initiated from widely separated but changes going on in the organism itself functionally interconnected body regions particularly in its muscles and their accessory Antagonistic reflexes interfered other reflexes organs (tendons joints blood vessels etc) One reflex was deferring interrupting or cutting Since in this field the stimuli to the receptors short another or precluding the latter altogether were given by the organism itself Sherrington from taking effect on the final common path In called it the proprioceptive field On the other all these forms of interference there was hand extero-ceptive was rich in the number and competition between the excitatory stimulus used variety of receptors in the body surface which for the one reflex and the excitatory stimulus for adaptation had evolved in it The excitation of the other And the precise form in which that receptors of proprioceptive field was related only occurred depended greatly on the time-relations secondarily to the agencies of the environment of application of the two stimuli competing and the primary action was excited by a receptor against each other The transition from one of the extero-ceptive field Therefore reflexes antagonistic reflex to another was one of active arising from proprioceptive organs came to be intervention (inhibition) For the interaction habitually attached and appended to certain between antagonistic reflexes in which one reflexes excited by extero-ceptive organs reflex action might be displaced by the other Between the proprioceptive and exteroceptive Sherrington called it interference Interference reflexes alliance occurred For example only occurred when reflexes were co-ordinated as flexion-reflex of the limb allied itself with the a form of successive combinations because reflex excited from the skin of the limb Thus antagonistic reflexes only interacted in such a the receptive field of flexion-reflex included not way There are two forms of successive only reflex arcs arising in the surface field but combination are alternating reflexes (rhythmic reflex arc arising in the depth of the limb reflexes) and compensate reflexes In sum alliance or coalition occurred between At length Sherrington discussed the four (1) individual reflexes belonging to the same factors determining the issue of the competition type reflex (2) certain reflexes originated by between antagonistic reflexes 27) receptors of different species but situated in the 1 Spinal induction in which there were same region of surface (3) certain reflexes successive induction rebound-effects in spinal belonging to proprio-ceptive organs secondarily reactions which tended to restore reflex excited by reflexes initiated at the body surface equilibrium (the three fields of reception extro-ceptive 2 Fatigue in reflexes when continuous intero-ceptive and proprio-ceptive) (4) certain excitation or frequent repetition were applied to

27) Ibid p 207-235

－ 16 － Ock-Joo Kim∶ Development of neurophysiology in the early twentieth century

the animal the spinal reflexes became weaker changed to suit passing requirements as the and might cease altogether Since it was not the functional points were sifted at great railway muscles which tired out but reflexes themselves junction The purpose of this mechanism was fatigue had intraspinal origin or central origin clear to Sherrington the common path The difference between inhibition and fatigue although economically subservient for many and was that reflexes ceasing under inhibition fade various purposes is adapted to serve but one off without change in frequency of the beat or in purpose at a time Hence it is a co-ordinating the duration of the beats but those under the mechanism and prevents confusion by restricting fatigue showed slower rhythm and a sluggish the use of the organ its minister to but one course for latter beats action at a time 28) 3 Intensity of reaction of the afferent arc was a decisive factor in the competition of afferent The motor area of the cerebral cortex arcs for possession of the final common path and integrative function of the brain As the intensity of stimuli increased it would inhibit other reflexes with greater frequency at While he studied the spinal reflex Sherrington final common path Intensity of stimuli as a rule became interested the role of motor cortex of the means intensity of reaction brain in the movement of the organism The 4 Species of reflex noci-ceptive nerves the first work that Sherrington had to do was to nerves conveying wide range of painful stimuli make an exact localization of the motor cortex could make strong affective reaction The previous researchers works on the Throughout his studies on reflexes functional topography of the brain had provided Sherrington could observe the high variability of much more understanding of the brain However reflex reaction from experiment to experiment it was still incomplete because of the complex He interpreted this phenomenon that this structure of the cerebrum and the limitation of functional activity itself caused from moment to the experimental approaches such as artificial moment the temporary opening of some stimulation Admitting the limitation of his connection and the closure of others In order to experiment with animals under narcosis he explain the mechanism he used a metaphor of applied electrical stimuli to brain to produce telephone This system of central nervous organ regularly certain localized movements from (grey matter) served as telephone exchanges certain restricted areas of its surface From moment to moment through the end-points Although Hitzig Fritsch and Ferrier made of the system were fixed the connections functional topography of motor cortex in the between starting points and terminal points were chimpanzee orang-utan and gorilla Ferrier said

28) Ibid p 234

－ 17 －醫史學 제10권 제1호(통권 제18호) 2001년 6월

that these areas had no exact line of demarcation the same side as the section If afferent roots from each other The cerebral fissures also was were severed the limb at once fall flaccid in a not functional boundaries The fact that structure local area of the convolution and sulcus showed marked From the study on decerebrated rigidity individual variety also made it difficult to draw question about muscle tonus was aroused exact line By that time the function of the Decerebrated rigidity showed a system of tonic precentral area was well known as a motor innervation in action Sherrington found that the center but Sherrington was not sure of the muscles predominantly affected in decerebrated function of post-central area (afferent area) rigidity were gravity-antagonists muscles which The inhibition of muscular contraction as well showed a certain degree of tonus He also as excitation was obtainable from the artificial discovered that tonus was a kind of reflex excitation of the cortex Many kinds of Continuous tonic reflexes were produced by the reciprocal inhibition such as reciprocal proprioceptors of limb and labyrinthine receptors innervation of antagonist eye-muscles reciprocal By the experiments he observed that destruction inhibition in other muscular groups and of labyrinth also delayed the onset of rigor motis reciprocal innervation in willed movements were and each labyrinth maintained tonus especially in obtained from the excitation of frontal area the neck and trunk muscles and in the corona radiata internal capsule and corpus extensor-abductor limb-muscles of the callosum Thus Sherrington surmised that seat homonymous side The proprioceptors and the of the inhibition was be in subcortical area labyrinthine receptors seem to have in common As a means of study of motor function of the this that both originate and maintain tonic brain Sherrington used decerebrate rigidity reflexes in the skeletal muscles 29) Essentially Decerebrated rigidity was a condition which tonic reflexes were concerned with the ensue on the removal of the fore brain by maintenance of attitude or posture in the skeletal transection at any of the various levels in the muscle whose function was movements or mesencephalon or thalamecephalon in its hinder steadily active antagonizing gravity Finally he part If the monkey was transected his brain concluded about reflex movements including below or in the lower half of the bulb flaccid tonus as following: paralysis happened in the body of the animal Administration of chloroform and ether if carried Two separable systems of motor innervation far abolished the rigidity Or section of the appear thus controlling two sets of musculature lateral column of the cord in the upper lumbar one system exhibits those transient phases of region abolished the rigidity in the hind-limb of heightened reaction which constitute reflex

29) Ibid p 330

－ 18 － Ock-Joo Kim∶ Development of neurophysiology in the early twentieth century

movements (phasic reflex system) the other the other hand brain received stimulation from maintains that steady tonic response which distant receptor organs such as visual olfactory supplies the muscular tension necessary to or auditory While the three receptive field gave attitude (tonic reflex system) … These two rise to direct confined reaction the receptor systems the tonic and phasic reflex systems organs controlled the body movement of the co-operate exerting influences complement to animal as a whole more than others each other upon various unit of musculature 30) Neural arcs from the distance receptors were particularly wide and far-reaching Usually What is the role of brain in integrating extensive internuncial paths belonged to neuro-muscular activity? how is it different from distance-receptors The internuncial path was the role of spinal cord? Sherrington reached itself a common path and therefore became a those questions and provided explanations mechanism of accommodation The According to Sherrington spinal reflexes distance-receptors induced anticipatory reactions movements suggested protective procreative or running before final or consummatory reactions visceral functions on the one hand and on the The series of actions of which the other the main movements of the progression distance-receptors initiated the earlier steps habitual to the animal On the other hand formed series much longer than those initiated by various movements elicitable from the motor other kinds of receptors The distant receptors cortex cared the significance of possible had the psychical quality termed the projicience responses to tactual auditory or visual stimuli of sensations Those distant receptors adapted The reflexes showed modification by cerebral odors light and sounds generated reactions to direction and control In other words during the the environmental objects at a distance The process of the combination of cortical and spinal projicience refered them without elaboration by nervous reactions spinal reflexes were modified any reasoned mental process to directions and by cerebral direction and control The dominance distances in the environment fairly accurately of the brain over the spinal cord came from the corresponding to the real directions and relation of the cortex to receptor organs - the distances of the their actual sources pre-eminent representation in it of the In relation to the evolution of the nervous distant-receptors The spinal cord received system Sherrington stressed the distance stimulation from three receptive fields the receptors Brain the very important organ in the proprioceptive field whose stimuli were events in higher grades of the animal scale was always the organism itself and two surface fields the part of the nervous system constructed upon extero-ceptive field and intero-ceptive field On and evolved upon the distant-receptor organs

30) Ibid p 302

－ 19 －醫史學 제10권 제1호(통권 제18호) 2001년 6월

Designating the cerebrum as the main ganglion After The Integrative Action of the Nervous of the distance-receptors 31) Sherrington System Sherrington published three fundamental concluded By the distance-receptors are studies They were papers on the stretch reflex initiated and guided long series of reactions of (1924) on central excitatory and inhibitory states the animal as a whole Other receptive reactions (1925) and on the motor unit (1930) The study integrate individual segments the reactions of of the motor unit in 1930-31 brought him the the distance-receptors integrate the whole series Nobel Prize in Physiology and Medicine in 1932 of segments It is in the sphere of reactions of Two of Sherrington s last comprehensive reviews these distance-receptors that the most subtle of muscle management at the spinal level are his and complex adjustments of the animal therefore 1931 Hughlings Jackson Lecture Quantitative arise 32) Management of Contraction in Lowest Level In 1933 in his book The Brain and its Coordination and the chapter seven of Reflex Mechanism Sherrington emphasized the Activity of the Spinal Cord (1932) When he importance of the role of the brain in movements retired in 1935 the Oxford school issued a of the organism At the same time he also series of influential papers on such topics as remarked the importance of inhibition in the after discharge summation recruitment postural action of the nervous system contraction and motor unit to illuminate the finer details of the reflex activity of the spinal I may seem to stress the preoccupation of the cord brain with muscle Can we stress too much that preoccupation when any path we trace in the For more than fifty years Sherrington studied brain leads directly or indirectly to muscle The a vast field of neuroanatomy and physiology By brain seems a thoroughfare for nerve action establishing basic concepts terms and principles passing on its way to motor animal It has been his works laid a foundation of modern remarked that Life s aim is an act not a neuro-physiology Sherrington s contributions to thought To-day the dictum must be modified to neurophysiology can be regarded as admit that often to refrain from an act is no neuro-physiology s watershed in several ways less an act than to commit one because First of all he provided integrated knowledge inhibition is coequally with excitation a nervous which connected the structure of the nervous activity 33) system to its function Before Sherrington anatomical and histological studies such as

31) Ibid p 351 32) Ibid p 348 33) Charles S Sherrington Epilogue Selected Writings of Sir Charles Sherrington ed by D Dennt Brown 1932 (Paul B Hoeber New York) p 515

－ 20 － Ock-Joo Kim∶ Development of neurophysiology in the early twentieth century

studies on nerve cells had little relation to the tem His unique and significant conception of physiological studies Devoting more than ten nervous integration carried the first years to meticulous studies on the neuroanatomy comprehensive experimentally documented he paved a road for his reflex studies Secondly explanation of how the nervous system through he established the methodology to research on the unit mechanism of reflex action produces an the nervous system which is the most complex integrated motor organism These watershed system in the body By reducing the complex achievement made his colleagues to designate system into unit he could unveil basic him as the main architecture of the nervous characteristics of nervous function After system the supreme philosopher of the grasping fundamental knowledge at the basic nervous system the author of the Principia level of the nervous system he moved on more of physiology and the man who almost complicated phenomena based upon previous data singlehandedly crystallized the specific field of and new observation Many scholars before him neurophysiology 34) could not succeed as Sherrington because they could not overcome the difficulties arising from key words Sherrington(1857-1952) neurophysiology the complexity of the nervous system Thirdly neuroanatomy experimental medicine central Sherrington laid down a fruitful guideline for nervous system investigators of the nervous system by providing the new conception about the whole nervous sys-

34) Swazey p 169

－ 21 －醫史學 제10권 제1호(통권 제18호) 2001년 6월

= 초록 =

20세기 초 신경 생리학의 발전 쉐링톤의 신경계의 통합적 작용 을 중심으로

김옥주*

챨스 스캇 쉐링톤(1857-1952)은 19세기 말로부터 20세기 중반에 이르기까지 신경생리학의 발전 에 크게 이바지하였다 실험과학의 방법론을 사용하여 축적된 방대한 지식을 토대로 그는 현대 신경생리학의 기초가 되는 주요한 개념들을 구축해 나갔다 저자는 이 논문에서 먼저 쉐링톤의 삶을 개관한 후에 그가 어떻게 신경해부학으로부터 연구를 시작하여 신경계 전반에 적용되는 개 념과 이론을 발전시켰는지를 살펴보았다 특히 그의 중요한 저작인 <신경계의 통합적 작용 (1906)>을 분석함으로써 쉐링턴이 신경생리학에 공헌할 수 있었던 주된 이유는 그의 철저한 실 험 뿐 아니라 다양한 실험결과들의 상호연관성을 파악하고 이론화해 나갈 수 있었던 그의 통합 적 사고방식이었음을 보였다 그의 책 제목이 나타내 주듯이 쉐링턴은 신경계의 통합적 특성을 파악했을 뿐 아니라 자신과 다른 연구자들의 업적을 통합하여 근대 신경생리학의 기초를 놓았 던 것이다

색 인어 챨스 스캇 쉐링톤 신경생리학 신경해부학 19세기 말 20세기 초 실험의학 신경계 ______* 서울대학교 의과대학 의사학교실

－ 22 －