Charles Scott Sherrington's Integrative Action: a centenary notice

One hundred years ago Charles Scott Sherrington (1857– 1952), Holt professor of physiology in the University of Liverpool, chose as his subject for the Silliman Lectures for 1904 at Yale University ‘The Integrative Action of the Nervous System’; two years elapsed before they were published.1 The yearly series honoured a professional chemist, Benjamin Silliman (1779–1864), who lectured in mineralogy and geology and for his wide interest in natural history had been given an honorary MD. The lectures introduced the term integration into scientific neurology. Sherrington pointed out that reflexes had to be goaldirected, and that ‘the purpose of a reflex serves as legitimate and urgent an object for natural inquiry as the purpose of colouring of an insect or blossom’. His work and his emphasis was on spinal reflexes for he recognized that the spinal cord provides the simplest portion of the mammalian nervous system and yet displays examples of all its synaptic functions. Information, he realized, is transmitted between nerve cells by contact, for which he had introduced the term synapse in 1897 when Michael Foster invited him to revise the chapters on the nervous system for the seventh edition of his Textbook of Physiology. Santiago Ramón y Cajal (1852– 1934) ‘solved at a stroke the great question of the direction of the nerve currents in their travel through the brain and spinal cord’, showing that it was unidirectional. In the reflex arc, the ‘wiring diagram’ of the spinal reflexes, afferent (sensory) and efferent (motor) elements were related at centres in the grey matter by synaptic contacts between the neurons. Sherrington concentrated on the mechanisms whereby excitatory and inhibitory processes, initiated by different inputs, interact to grade the output of a pool of motoneurons for different purposes. The central issue in the classic experiments he had made with isometric muscle preparations in spinal animals concerned the interaction between excitation and inhibition. That reflex contraction of knee extensor muscle in the decerebrate preparation could be immediately and dramatically cut short by sensory stimulation he found particularly impressive. Excitation and inhibition were shown to be graded states of opposite character, capable of what looked like algebraic summation of opposites (plus and minus signs) when they clashed on the same neuronal membrane, a prophecy proved to be true when the intracellular microelectrode invented by Ling and Gerrard was inserted into spinal motoneurons. Synaptic excitation and inhibition, as produced by appropriate reflexes, were shown to elicit opposite changes in membrane potential of the cell, excitation depolarizing it, inhibition repolarizing or hyperpolarizing it. Changes in ionic permeabilities are now known to explain these electrical changes brought about by synaptic action, which Sherrington felt assured were electrical rather than chemical in nature—as was proved by Otto Loewi (1873–1961) and Henry Dale (1875–1968), who shared the Nobel Prize in 1936. The spinal reflex, in Sherrington’s words, is a very elementary ‘item of behaviour’, but it had to be elementary to allow detailed examination and to inspire the subsequent analysis that led to his understanding of synaptic action. The stretch reflex might be a ‘convenient fiction’ but it and its fellow spinal reflexes provided the platform from which to examine how motor mechanisms are progressively organized, how the different cortical, subcortical, cerebellar and spinal centres interact in initiating and controlling movement, how sensory receptors operate reflexes, and how neuronal programmes—old and new—are used by higher centres. Reviewing the ‘physiological and psychical signs of nervous activity’ Sherrington argued that ‘physiology and psychology, instead of prosecuting their studies, as some now recommend, more strictly apart one from another than at present, will find it serviceable for each to give to the results achieved by the other even closer heed than has been customary hitherto. ’ In a foreword when the book was reprinted in 1947 ‘without any change whatsoever in the text’, the author returned to the realization that ‘the biological function of the physico-psychical liaison enhances the organism’s power of disposing of its acts’, remarking that ‘each of the two achieves its aim only by reason of a contact utile between them. And this liaison can rank as the final and supreme integration completing the individual. But the problem how that liaison is effected remains unsolved; it M E D IC A L H IS T O R Y