Statistical factors involved in neuromuscular facilitation and depression

When a series of impulses arrive at the nerve-muscle junction, the end-plate potentials (e.p.p.) which they produce are not constant but vary in size, depending on the number and frequency of the stimuli. Two main types of phenomena have been observed: (a) a progressive increase of the e.p.p. (facilitation, post-tetanic potentiation) and (b) a phase of depression (Wedenski-inlilbition, junctional fatigue). The present paper is concerned with the stage of neuromuscular transmission at which facilitation and depression occur and with the question whether 'quantal' changes of e.p.p. amplitude are involved. It has been suggested that the progressive synaptic changes during repetitive stimulation are due to a variation in the output of acetylcholine (ACh) from the motor nerve endings rather than to post-synaptic events (e.g. Feng, 1941 b; Hutter, 1952; Eccles, 1953, p. 89 seq.). In view of the recent evidence indicating that ACh release occurs in discrete quanta, it is of interest to inquire whether a functional change of ACh output takes place at quantal or molecular level, involving either the number or the size of the miniature units of which the end-plate response is composed.