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HANDBOOK OF PHYSIOLOGY 



NEUROPHYSIOLOGY II 



tissue." Further, since conduction throua;h smooth 

 muscle is not inhibited by local anesthetics (38, 60, 

 146, 393) or by ganglionic blocking agents (60, 126, 

 144, 379), it is doubtless myogenic and therefore 

 does not require conduction through a peripheral 

 nerve net (148, 377). 



Two further considerations oppose the acceptance 

 of such a nerve net. First, the innervation of smooth 

 muscle in certain organs, such as the heart (370), 

 the cat retractor penis (332), certain small blood 

 vessels (300), the cat submaxillary gland (130, 299) 

 and fish melanophores (335), by two sets of fibers 

 with antagonistic actions seems incompatible with a 

 syncytially connected peripheral net (377). Second, 

 the assumption that the terminal parts of the auto- 

 nomic innerv'ation structure may remain more or less 

 intact after degenerative transection of the post- 

 ganglionic nerves, a correlate to the syncytium theory, 

 does not fit the evidence presented by von Euler and 

 his associates (171, 424, 425, 427), strongly indi- 

 cating that the adrenergic transmitter is accumu- 

 lated in the nerve terminals and clearly showing 

 that it disappears when the postganglionic fibers 

 degenerate. 



The neurohistological investigation referred to 

 above led to a new concept of the innervation of 

 autonomic effectors according to \vhich the inner- 

 vation takes place by means of the autonomic ground 

 plexus, a plexus of axon ramifications embedded in a 

 fine-meshed network of anastomosing protoplasmic 

 strands formed by the terminal Schwann plasmodium 

 and directly superimposed on and probably contact- 

 ing all effector cells. The view that the plexvis is the 

 real inner\-ation structure is partly hypothetical as it 

 is based on the assumption that the plexus is a closed 

 terminal formation. The structure of the plexus re- 

 garded as a whole strongly supports this concept. 



The morphological arrangement of the autonomic 

 ground plexus does not in itself give any clue to 

 the functional organization of effector innervation. 

 Cannon, Rosenblueth and their associates (cf. 76, 

 361, 368, 369) made the basic experiments necessary 

 for an understanding of this organization more than 

 20 years ago, and they developed a theory giving a 

 logical explanation to the phenomena observed. 

 This theory is founded on the assumption that only 

 some of the effector cells are directly innervated. 

 The chemical mediator liberated by the nerve im- 

 pulses in or at these 'key cells' diffuses to the non- 

 inner\ated cells; this free diffusion explains their 

 fundamental obser\ation that spatial and temporal 

 summation are quantitatively interchangeable in 



autonomic effectors, the response being dependent 

 on the numljer of impulses per unit time only and 

 not on the number of activated ner\e fibers. In con- 

 trast to voluntary muscle, autonomic neuroeffectors 

 are thus not organized in units, but the innervation 

 is quite diffuse. Xow it is obvious that the key cell 

 principle is no necessary part of the theory and may 

 l)e dropped, as apparently it has been by Rosen- 

 blueth (362). The essential parts are the theoretic 

 aspects of the liberation, diffusion and action of the 

 mediator. Much evidence in fa\or of the Cannon- 

 Rosenblueth theory has accumulated (cf. 362), and 

 certainly any new theory concerning the innervation 

 of autonomic effectors must be able to account for 

 the phenomena of spatial and temporal summation 

 in the effectors. 



Although leakage of the adrenergic mediator into 

 the blood and diffusion within autonomic effectors 

 have been demonstrated to occur, it may be that this 

 diffusion does not have anv phvsiological signifi- 

 cance for the innervation of an effector system. Direct 

 evidence concerning this proijlem has been obtained 

 from studies of the cytologically demonstrable cell 

 reactions evoked by reflex stimulation of the nerv-ous 

 centers of the adrenal medulla (206) and of the 

 submaxillary gland (207) with intact innervation or 

 partial denervation. Lack of space does not permit 

 more than a brief summarv, but a detailed discussion 

 of the validity of the conclusions is found in the 

 original papers. (.See also Chapter \'II by von Euler 

 on autonomic transmission in this work.) 



Both in the cholinergic systems and in the adrenergic 

 system examined in the experiments, the results speak 

 for the view that the cell complexes are organized in 

 units which may be submaximally stimulated or 

 drop out of activity altogether when the glands are 

 partially denervated. The presence of more or less 

 submaximally activated complexes in spite of intense 

 stimulation, producing exhaustion changes in cells 

 with intact innervation, indicates that each unit 

 receives nerve terminals from several neurons. The 

 results further speak strongly against the assumption 

 that transmitter diffusion is an important innervation 

 mechanism. For instance, denervated cell complexes 

 do not show an\ activation through mediator diffu- 

 sion from highly active complexes immediately ad- 

 jacent to the denervated ones in spite of very intense 

 stimulation of long dvu-ation, denervation super- 

 sensitivity and cholinesterase inactivation. These 

 results are oijviously inconsistent with the transmitter 

 diffusion theory of Cannon and Rosenblueth. How- 

 ever, it is possible to form a new concept of autonomic 



