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Thirst-associated preoptic neurons encode an aversive motivational drive

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Science  15 Sep 2017:
Vol. 357, Issue 6356, pp. 1149-1155
DOI: 10.1126/science.aan6747

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Thirst-quenching neural mechanisms

To maintain homeostasis, physiological imbalances produce motivational drives. Thirst is one of the strongest drives. Allen et al. identified a distinct population of neurons in a brain region called the median preoptic nucleus that are activated during thirst (see the Perspective by Gizowski and Bourque). The activity of these neurons integrates the recent history of water intake and adaptively regulates goal-directed behavior. When thirsty, animals consume water, which in turn reduces the aversive activity of the neurons. This action is repeated until the level of aversion falls below the threshold necessary to evoke this behavior.

Science, this issue p. 1149; see also p. 1092

Abstract

Water deprivation produces a drive to seek and consume water. How neural activity creates this motivation remains poorly understood. We used activity-dependent genetic labeling to characterize neurons activated by water deprivation in the hypothalamic median preoptic nucleus (MnPO). Single-cell transcriptional profiling revealed that dehydration-activated MnPO neurons consist of a single excitatory cell type. After optogenetic activation of these neurons, mice drank water and performed an operant lever-pressing task for water reward with rates that scaled with stimulation frequency. This stimulation was aversive, and instrumentally pausing stimulation could reinforce lever-pressing. Activity of these neurons gradually decreased over the course of an operant session. Thus, the activity of dehydration-activated MnPO neurons establishes a scalable, persistent, and aversive internal state that dynamically controls thirst-motivated behavior.

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