Differential release of acetylcholine from the hypothalamus and mesencephalon of the monkey during regulation

1. In unanaesthetized monkeys acclimated to primate chairs, 101 isolated sites in the hypothalamus and mesencephalon were perfused at a rate of 30-50 mul./min by means of push-pull cannulae. The perfusate, which contained an anticholinesterase, was assayed for acetylcholine (ACh) activity on the guinea-pig ileum in the presence of neostigmine.2. The body temperature of each animal was monitored continuously during an experiment by colonic and brain thermistors. To alter the ambient temperature by 15-20 degrees C, either a stream of warm air was passed over the monkey's trunk or containers of ice were placed in its chair chamber to cool the same region.3. Assays of the effluent revealed that the release of ACh varied according to the ambient temperature as follows: elevated only during cooling; elevated only during warming; elevated by both thermal stimuli; suppressed only by cooling; suppressed only by warming; suppressed by both thermal stimuli; elevated during cooling but suppressed by warming; and elevated by warming and suppressed by cooling.4. A composite anatomical ;mapping' of all perfusion sites revealed that in response to either peripheral cooling or warming, the output of ACh varied at only 36% of all sites anterior to the mid-hypothalamic plane, but at 65% of those loci caudal to this coronal plane.5. In the anterior, preoptic area, cooling enhanced the output of ACh at 88% of the active releasing sites, whereas warming reduced the release of ACh at 80% of these perfusion loci. Posterior to this region, ACh release was elevated by cooling at about half of the active releasing sites, but lowered by warming at nearly every active perfusion locus. Within the mesencephalon, the ratio of the temperature-induced change in ACh release was similar but in an opposite direction, since the level of ACh in the effluent collected from two out of three sites was augmented by cooling, but diminished by warming.6. These results provide additional evidence for the neurochemical model of Myers & Yaksh (1969), which suggests that a cholinergic pathway originating in the anterior, preoptic region transmits efferent signals for heat production. Further, within the posterior hypothalamic area as well as in the mesencephalon of the monkey, the characteristics of the ACh releasing sites reflect a function delegated primarily to heat gain, although evidence of a cholinergic pathway for the heat loss system is also presented.