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SUMMARY1. 5-Hydroxytryptamine (5-HT) and various 5-HT antagonists have been applied micro-electrophoretically from multibarrelled micropipettes into the environment of single neurones in the post-sigmoid and suprasylvian gyri of the cat cerebral cortex.2. In unanaesthetized animals (encephale isole) a high proportion of neurones (30 %) were excited by 5-HT. This excitation usually had a rapid onset and was seen both in spontaneously active neurones and in otherwise quiescent neurones in which firing was induced by L-glutamate. Some neurones were so sensitive that the uncontrolled diffusion from micropipettes was sufficient to excite them. More cells were excited by 5-HT applied as a cation from solutions of the bimaleate salt than when solutions of the creatinine sulphate salt were used.3. In a high proportion of cells (33 %) spontaneous firing or amino acid excitation was depressed by 5-HT. 4. A mixed effect was seen in a small proportion (6 %) of the cells tested; usually 5-HT caused an excitation initially which was followed by a depression. In other cells, desensitization occurred, and the excitatory effect of 5-HT was diminished or lost. In two cells, however, the depression was reversibly prevented by these antagonists.8. Some cells tested with 5-HT were also tested with ACh or (-noradrenaline. The response of a cell to ACh was not significantly related to its response to 5-HT. The degree of correlation between the responses to noradrenaline and 5-HT was large, but not statistically significant with the small number of cells studied. 9. The effects of 5-HT on cells in animals anaesthetized with oc-chloralose did not differ significantly from its effects in unanaesthetized preparations. It is suggested that the use of this anaesthetic may prove a useful alternative to unanaesthetized preparations.10. The systemic injection of small quantities of thiopentone sodium selectively and reversibly reduced the sensitivity of some units to excitation by 5-HT at a time when the response to glutamate was unaffected. On other occasions, the 5-HT excitation was unaffected, though the response to glutamate was reduced.11. These results are discussed in relation to the possible nature of the 5-HT receptors in the cerebral cortex, and the interfering effects of anaesthesia on the response of brain cells to potential transmitter substances.

The release of acetylcholine from rat and guinea-pig isolated diaphragm preparations stimulated through the phrenic nerve was optimal at 370 in Krebs solution with 5x 10-6 neostigmine methylsulphate. The amount of acetylcholine released by a 20 min. tetanus was reduced by cooling. At frequencies of stimulation above 6/sec. the release was less than that predicted. This " failure " was unaffected by the addition of 1 x 10-6 choline. The acetylcholine release declined with continued stimulation at 25/sec. In the absence of nerve stimulation, there was a small continuous resting release of acetylcholine which seemed to originate in the muscle fibres. These results are discussed in the light of current electrophysiological knowledge of the quantal release of acetylcholine.Nearly a quarter of a century has passed since Dale and his colleagues first showed that acetylcholine was released at the neuromuscular junction by motor nerve stimulation, and could be measured directly in the extracellular fluid if steps were taken to prevent its destruction by cholinesterase (Dale and Feldberg, 1934; Dale, Feldberg, and Vogt, 1936). Since that time it has been generally accepted that acetylcholine is the chemical mediator of nerve impulses at all neuromuscular junctions. Recently, Dale's observation has been confirmed and extended by others, in a perfused muscle preparation (Emmelin and MacIntosh, 1956) and in isolated diaphragm preparations (Burgen, Dickens and Zatman, 1949;Barnes and Duff, 1954;Brownlee, 1957; Brooks, 1954).The present experiments are concerned with the factors which modify the amounts of the transmitter released from motor nerve endings; and in particular with the effect of changes in the frequency and duration of stimulation, changes in temperature and the presence of choline on acetylcholine release.

6. The most usual effect seen with 5-HT was depression, though several units were found to be excited. Some of the units tested with 3-hydroxytyramine (dopamine) or noradrenaline were found to be depressed.

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