430 ANNALS NEW YORK ACADEMY OF SCIENCES 



eserinized, stimulated ganglia or muscle suggested the additional hy- 

 pothesis that, normally, acetylcholine is removed by being rebuilt 

 rapidly to a precursor and that cholinesterase merely acts as a barrier, 

 to prevent diffusion of acetylcholine away from the synapse.**^ Further 

 additions to this hypothesis were needed, in order to explain the effects 

 of eserine and curarine on end-plate potentials.* It is unsatisfactory 

 that the acetylcholine hypothesis has had to be reconciled with new 

 experimental evidence, by thus making subsidiary ad hoc hypotheses, 

 which have not been independently testable. The most recent develop- 

 ment of the acetylcholine hypothesis*'^ is essentially a special type of 

 the electrical hypothesis, for it postulates that electrical transmission 

 across the synapse excites the postsynaptic liberation of acetylcholine, 

 which, in turn, sets up the synaptic potential. 



(ii) Most expressions of the electrical hypothesis of synaptic trans- 

 mission have merely stated that the electrical currents of the pre- 

 synaptic impulses set up impulses in the post-synaptic cell, much as one 

 segment of a nerve excites the next.^°' ^^' ^°' ^^' '^^ The attempt at pre- 

 cise formulation by Lapicque (the isochronism hypothesis) has had 

 to be modified so much by the recognition of the significance of addi- 

 tional factors (relative durations of the pre- and post-synaptic re- 

 sponses,"'^ the rheobase of the post-synaptic celP^) , that it now states 

 little more than the above vague formulation. Thus, the electrical 

 hypothesis is unsatisfactory (indeed, virtually useless), because it is 

 so vaguely expressed that it fails to give predictions that would be a 

 fertile source of experimental tests. 



2. RECENT EXPERIMENTAL SUPPORT FOR AN 

 ELECTRICAL HYPOTHESIS 



The need for a more developed electrical hypothesis has now become 

 urgent, because the following recent investigations have indicated that 

 acetylcholine plays but a subsidiary role at ganglionic synapses, and a 

 negligible role at spinal cord synapses. With muscle, too, there are 

 indications that electrical transmission may play an important part. 



(i) A detailed study^- -'^ of the electrical responses of eserinized 

 ganglia (normal and curarized) revealed an excitatory action, pro- 

 longed for several seconds after repetitive stimulation and attributable 

 to acetylcholine. However, this prolonged action was so weak that 

 the summation of about 20 volleys in (juick succession was needed to 

 make it sufficiently strong to excite normal, fully eserinized ganglion 



• Cf. Eccles, J. C, B. Katz, & S. W. Kuffler.": 227-8. 



