THE HISTORICAL DEVELOPMENT OF NEUROPHYSIOLOGY 



to suggest that adrcnin "might then be the chemical 

 stimulant liberated on each occasion when the im- 

 pulse arrives at the periphery." Langley (121), who 

 was at that time professor of ph\ siology at Cambridge, 

 recognizing that in some smooth muscle the action 

 both of sympathetic nerve stimulation and of adrenin 

 was to produce contraction whereas in others the 

 result was a relaxation, postulated the existence of 

 two kinds of receptor substance — excitatory and in- 

 hibitory. That adrenin mimicked sympathetic action 

 was then accepted. 



The possibility of a chemical mediator for the 

 vagal action on the heart was explored experi- 

 mentally in several centers. Bottazzi (122), Martin 

 (123) and Howell (124) thought the agent must be 

 potassium, Dixon (125) that it was muscarine, an 

 alkaloid closely related in structure to the cholines. 

 These substances had been shown to be active in sev- 

 eral puzzling ways. In 1906 Hunt & Taveau (126) 

 had demonstrated the extremely potent effect of 

 acetylcholine on arterial pressure, and by 1914 the 

 work of Dale (127) was already pointing so strongly to 

 acetylcholine being the drug involved in parasympa- 

 thetic action, that he described it as 'parasympatho- 

 mimetic' Direct experimental proof was lacking that 

 a chemical substance excreted as a result of nerve 

 stimulation would in fact activate a tissue in a similar 

 way, although the hypotheses both for epinephrine in 

 the sympathetic and acetvlcholine in the parasympa- 

 thetic system seemed highly plausible. 



The direct proof came from the brilliant researches 

 of Otto Loewi (128) in which he demonstrated that 



12!. Langley, John Newport (1852-1906). On the reaction 

 of cells and of nerve-endings to certain poisons, chiefly as 

 regards the reaction of striated muscles to nicotine and to 

 curare. J. Physiol. 33: 374, 1905. 

 Bottazzi, P. Arch. Physiol. 882, 1896. 

 Martin, E. G. The inhibitory influence of potassium 

 chloride on tlie heart, and the eff^ect of variations of 

 temperature upon this inhibition and upon vagus in- 

 hibition, .-im. J. Physiol. II : 370, 1904. 

 Howell, VV. H. Vagus inhibition of the heart in its re- 

 lation to the inorganic salts of the blood. Am. J. Physiol. 

 15: 280, 1906. 



Dixon, W. E. On the mode of action of drugs. Med. Mag. 

 16:454, '907- 



ijfi. Hunt, R. and R. de M. Taveau. On the physiological 

 action of certain cholin derivatives and new methods for 

 detecting cholin. Bril. A/. J. ■2: 1788, 1906. 



127. Dale, H. H. The action of certain esters and ethers of 

 choline, and their relation to muscarine. J. Pharmacol. 

 & Exper. Therap. 6: 147, 1914. 



128. Loewi, O. Uber humorale Ubertragbarkeit Herz- 

 nervenwirkung. .^rch. ges. Physiol. 189: 239, 192 1. 



122 

 123 



124. 



125- 



^^ 



FIG. 18. Lift: an early representation of spinal roots and 

 tracts as drawn by Domenico Mistichelli in his Traltalo dtU'.i/io- 

 plessia, 1 709 (from the copy in the Boston Medical Library by 

 courtesy of Dr. Henry Viets). Mistichelli is considered to be 

 one of the first workers to recognize the crossing of the pyra- 

 mids. Right: the crossing of the pyramids was described and 

 experimentally demonstrated on injury to the brain in dogs by 

 Pourfour du Petit, a pupil of Duverney. His drawings are from 

 his Lettres d'un medicin, 1 727. (From the copy in the Bibliotheque 

 Nationale. Reproduction by courtesy of Dr. Auguste Tournay.) 



the fluid bathing a frog's heart which had been stimu- 

 lated through its vagus had an inhibitory action on 

 the beat of another heart. He named the agent 

 'Vagusstoffe.' From this cla.ssic observation, one of 

 the landmarks of physiology, experimentation spread 

 cut to the examination of other tissues, other nerves, 

 and other mediators and inhibitors, and forms one of 

 the wide fields of today's research. With the recogni- 

 tion of neuroneural synapses the problem of trans- 

 mission was carried from the peripheral neuromuscu- 

 lar svstem into the central nervous svstem. 



SPINAL CORD AND REFLEX ACTIVITY 



The functions of the spinal cord long remained an 

 enigma to the early physiologists. For as long as the 

 belief persisted that every nerve in the body required 

 its own canal leading directly from the brain in order 

 to insure its supply of animal spirits, the spinal cord 

 appeared to be merely a bundle of nerve fibers 

 grouped together. In other words, it was a prolonga- 

 tion of the peripheral nervous system channeling into 

 the brain. 



