PERIPHERAL AUTONOMIC MECHANISMS 



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innervation wliich may give an alternative explana- 

 tion for the observations of temporal and spatial 

 summation in autonomic efTector systems and further- 

 more an explanation for some of Rosenblueth's 

 observations not accounted for in his theory. This 

 concept, which also gives a reasonable explanation 

 of the puzzling morphological construction of the 

 innervation structure, especially the existence of 

 several axons in each strand of the plexus, may be 

 briefly summarized as follows. 



The innervation structure consists of the auto- 

 nomic ground plexus within which each terminal 

 axon ramification has a certain extension and in its 

 course innervates a certain number of cells or cell 

 complexes forming a neuroeffector unit. To each 

 unit, however, sevCTal postganglionic neurons con- 

 verge, the terminal axon ramifications of which run 

 within the same strands of the ground plexus. By the 

 overlap thus present in the innervation structure the 

 response of the effector system may be modified by 

 both temporal and spatial summation. 



It is obvious that this concept in no way contra- 

 dicts the arguments and concepts of Cannon and 

 Rosenblueth concerning the liberation and action of 

 the chemical mediator. The mediator diffusion 

 principle js replaced by a convergence principle on 

 the basis of which several experimental results in- 

 consistent with the diflfusion theory may be logically 

 explained. As the discrepancies have not been pointed 

 out by Rosenblueth, some of them will be briefly 

 discussed. From the crucial experiments on temporal 

 and spatial summation in the nictitating membrane 

 made by Rosenblueth & Rioch (369) it is clearly seen 

 that, according to the diffusion theory, the mediator, 

 locally liberated on stimulation of large or small 

 fractions of the nerves, must be assumed to have a 

 free diffusion to remote cells which is as complete 

 and of the same effective magnitude when large or 

 very small quantities are diffusing and when the 

 diffusion distance is long or short. This seems quite 

 unreasonable. The convergence principle, on the 

 other hand, gives an adequate explanation to the 

 experimental data; the spatial relationship between 

 the site of release and the site of action of the mediator 

 does not change when only a fraction of the nerves 

 instead of all are stimulated. It can be seen from the 

 same experiments that the mediator locally liberated 

 by impulses in only a fraction of the nerves to the 

 nictitating membrane must, according to the diffusion 

 theory, be assumed to diffuse freely to all the muscle 

 cells, even at the lowest stimulation frequencies 

 (less than i per sec). The results obtained in exactly 



the same type of experiments with chronic partial 

 denervation of the membrane (246) are quite in- 

 consistent with this view and do not indicate a 

 mediator diffusion until a relatively high stimu- 

 lation frequency is used. Finally, Rosenblueth & 

 Rioch (369) have shown that cholinergic systems 

 behave in the same manner as adrenergic systems with 

 regard to temporal and spatial summation. This may 

 be said almost to invalidate the whole diffusion 

 theory. If it seemed unreasonable to have the same 

 free diffusion of the adrenergic transmitter under all 

 the experimental conditions examined, it certainly 

 seems highly improbable to have such a diffusion 

 mechanism in cholinergic effectors with their high 

 power of destroying acetylcholine. The view that 

 there exists a considerable convergence of nerve 

 terminals from different postganglionic neurons to 

 one effector cell group has strong support from a 

 recent study of the electrophysiology of the cat's 

 submaxillary gland (299). 



It might be argued that the mediator overflow 

 found to occur on stimulation of adrenergic nerv-es 

 speaks in favor of the view that there is a considerable 

 transmitter diffusion within autonomic effectors, a 

 diffusion which has even been considered to make the 

 concept of innervation quite illusory. Admittedly 

 there is as yet no possibility of generalizing the 

 innervation theory launched above to hold for all 

 effector systems. However, the existence of the same 

 innervation structure in widely different effectors 

 and the possibility of giving a more adequate ex- 

 planation of the summation mechanism in cholinergic 

 as well as in adrenergic systems suggest a more general 

 applicability of the theory. Furthermore, evidence is 

 accumulating for the view that the adrenergic trans- 

 mitters are to a large extent inactivated locally at 

 the site of their release and that no significant ac- 

 cumulation or overflow take place on stimulation of 

 adrenergic nerves with frequencies within the physi- 

 ological range (81-83, 151). Quantitative determi- 

 nation of the norepinephrine output from the spleen 

 on stimulation at different frequencies strongly 

 supports this view (53). 



There is good evidence that the chernical mediators 

 are produced by and acciimulated in the autonomic 

 nerve termin als (cf. 362, 423-425). All the available 

 data also speak for the view of von Euler that the 

 mediators are concentrated in high amounts in the 

 terminals. In fact, the amounts are so high that it 

 seems necessary to postulate that the individual 

 endings, each constituting a transmitting junctional 

 structure, cannot be tiny knobs or small axon ex- 



