J. C. ECCLES 347 



system. However, there may be quantitative differences, the synapses at 

 higher levels being more sensitive, relatively few impulses producing 

 large and prolonged plastic changes. 



On account of the very long time scale of the synaptic changes pro- 

 duced by use and disuse it would be extremely difficult to discover their 

 nature by direct investigation. However, in many respects post-tetanic 

 potentiation resembles the effect of excess usage, and it can be readily 

 investigated. 



With post-tetanic potentiation of neuromuscular transmission a highly 

 significant finding is that the potentiation is paralleled by an increased 

 frequency of the quantal emission of transmitter substance from the 

 presynaptic endings (Brooks, 1956; Liley, 1956; Hubbard, 1959), as 

 signalled by an increased frequency of the miniature endplate potentials 

 (cf. Katz, 1958). Electron microscopy has revealed a dense assemblage of 

 the so-called synaptic vesicles in the presynaptic terminal, and it is highly 

 probable that the quantal emission ot transmitter substance is due to the 

 bursting of these vesicles into the synaptic cleft. Hence, an attractive 

 explanation is available for post-tetanic potentiation: the repetitive 

 presynaptic stimulation causes the mobilization of these synaptic vesicles 

 close to the synaptic surfice {cf. Palay, 1956), so that not only is their 

 rate of spontaneous emission increased, bui" there is also an increase in the 

 number emitted by a presynaptic impulse (cf Eccles, 1957). 



However, there is also good experimental support for an alternative 

 explanation of post-tetanic potentiation: the repetitive presynaptic 

 stimulation is followed by an increased membrane potential of the presy- 

 naptic terminals, with the consequence that the presynaptic impulse is 

 increased in size and so synaptic transmission is potentiated (Lloyd, 1949; 

 Eccles and Krnjevic, 1959 a, b). 



Presumably both of these postulated processes are concerned in post- 

 tetanic potentiation, but it seems most improbable that an increased 

 membrane potential of presynaptic fibres could account for the very pro- 

 longed increase that excess use causes in synaptic efficacy, or even for the 

 several hours of the residual potentiation displayed by disused synapses. 

 On the other hand it seems a likely possibility that changes in the popula- 

 tion or disposition of synaptic vesicles could account at least in part for 

 very prolonged changes in synaptic efficacy. 



Besides these physiological investigations into the effects ot excess use, 

 it is important to see whether electron microscopy reveals any structrual 

 changes in the presynaptic terminals. Already it has been reported that, 

 after several days of disuse brought about by complete darkness, there is 



