SUMMARY1. The recapture and re-use of choline formed by the hydrolysis of released acetylcholine (ACh) nerve terminals appear selectively to accumulate choline. 4. However, chronically decentralized ganglia accumulated as much choline as did acutely decentralized ganglia, and this was interpreted as indicating that at rest preganglionic nerve terminals do not selectively accumulate choline.5. Increased exogenous choline concentration increased the amount of radioactivity collected during nerve stimulation in the absence, but not the presence, of an anticholinesterase agent. The spontaneous efflux of radioactivity was little affected by changes in external choline levels. It is concluded that exogenous choline and choline made available from released transmitter compete for uptake into nerve terminals.

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6. The accumulation of surplus ACh no more than doubled the total ACh content of ganglia, but turnover of ACh continued when the total amount was constant. Surplus ACh may contribute to spontaneous ACh output from eserinized preparations.7. When ganglia were perfused with a medium containing high K+ (56 mM), surplus ACh was released.

Summary1 The experiments described in this paper tested the effect of acetylcholine (ACh), carbachol or preganglionic nerve stimulation on the release of ACh from the cat's perfused superior cervical ganglion; radioactive tracer methods were used. 2. When the ganglion's transmitter store of ACh had been labelled, radioactive ACh was released by nerve stimulation (5 Hz for 2 min), but there was no release by ACh (015-15 jg) or by carbachol (1-10 Mig) when these drugs were injected close to the ganglion. Perfusion with low or moderate concentrations of ACh (0-15-5 jug/ml) also failed to release ACh, but high concentrations (15-50 ,tg/ml) released a small amount of labelled material. There was no correlation between ganglion stimulation by ACh and release of radioactivity.3. Ganglion-blocking concentrations of ACh did not reduce the release of ACh during continuous nerve stimulation. 4. When resting (unstimulated) ganglia were perfused with 3H-choline and eserine, the extra ACh synthesized and stored by such ganglia (surplus ACh) was labelled. Preganglionic nerve stimulation (5 Hz for 2 min) did not release surplus ACh, but perfusion with ACh (05-15 pig/ml), or injection of carbachol (0O5-2-5 ytg) did. 5. Surplus ACh released by ACh or by carbachol did not contribute to the ganglion stimulating effect of either drug. 6. It is concluded that the presynaptic effects of ACh are not of physiological importance. IntroductionThe concept that the arrival of an action potential in a presynaptic nerve terminal results in the release of enough transmitter substance to effect synaptic transmission has been challenged by Koelle (1961Koelle ( , 1962). Koelle's hypothesis is that, at cholinergic synapses, a nerve impulse releases too little acetylcholine (ACh) to stimulate the postganglionic cell directly, but enough to prolong the state of depolarization of the presynaptic nerve terminals so that they discharge additional ACh which does effect transmission.This suggestion that there is a positive feed-back mechanism for release implies that exogenously applied ACh, or ACh-like agent, should release transmitter from presynaptic nerve endings, and some evidence has accumulated that this might be