ECCLES: ELECTRICAL THEORIES OF TRANSMISSION 451 



being a special example of the type with an initial anodal and terminal 

 cathodal action; the only type in which a significant excitatory action 

 is exerted. 



1.4) Electrical recording from the isolated neuro-muscular junction 

 shows that the motor end-plate is specialized to give local responses 

 without the all-or-nothing breakdown of propagated impulses. Im- 

 pulse initiation appears to be produced by a secondary catelectrotonus 

 in the surrounding membrane. 



The present hypothesis makes three main assumptions: 



A. A schematized formulation is made of the essential geometrical 

 relationship of the membranes of the pre- and post-synaptic elements, 

 as revealed by histological and electrical investigation. 



B. The electrical properties of the pre- and post-synaptic surface 

 membranes resemble those observed for peripheral nerve and muscle 

 (see (.1), above j. 



C. The membrane of the immediate post-synaptic region is special- 

 ized, so that large and graduated local responses are set up by catelec- 

 trotonic polarization (see (2) and (4), above). 



On these basic assumptions, it is shown that a pre-synaptic im- 

 pulse sets up electric currents exerting an initial anodal and later 

 cathodal action on the post-synaptic membrane. The latter action, in- 

 tensified by rectification, sets up a local response (part 4, C), which, in 

 turn, acts as a relatively prolonged cathodal focus, from which spreads, 

 electrotonically, the synaptic potential of the effector cell. Finally, 

 the initiation of impulses by this synaptic potential appears to be ex- 

 plicable, simply, as the action of a catelectrotonus. 



This hypothesis is shown to offer satisfactory explanations of many 

 fundamental observations on synaptic transmission: irreversibility; 

 synaptic delay; time-course of junctional potential; brief impedance 

 loss at end-plates; dorsal root potentials of the spinal cord; some of 

 which were hitherto inexplicable in detail. 



On the other hand, the hypothesis encounters difficulties in explain- 

 ing the actions of curare and of anti-cholinesterases on synaptic trans- 

 mission in ganglia and skeletal muscle. The action of curare may be 

 explained, if it is assumed that it depresses the electrical excitability of 

 the post-synaptic membrane, as well as its pharmacological excitabil- 

 ity. It is argued that this assumption has not yet been tested. The 

 action of anti-cholinesterases is attributed to the intensification and 

 prolongation of the action of acetylcholine, to which the hypothesis as- 

 cribes a subsidiary role, as a transmitter at synapses of ganglia and 

 skeletal muscle. A further difficulty appears to arise in the explana- 



