Activation of lateral hypothalamic area neurotensin-expressing neurons promotes drinking

Animals must ingest water via drinking to maintain fluid homeostasis, yet the neurons that specifically promote drinking behavior are incompletely characterized. The lateral hypothalamic area (LHA) as a whole is essential for drinking behavior but most LHA neurons indiscriminately promote drinking and feeding. By contrast, activating neurotensin (Nts)-expressing LHA neurons (termed LHA Nts neurons) causes mice to immediately drink water with a delayed suppression of feeding. We therefore hypothesized that LHA Nts neurons are sufficient to induce drinking behavior and that these neurons specifically bias for fluid intake over food intake. To test this hypothesis we used designer receptors exclusively activated by designer drugs (DREADDs) to selectively activate LHA Nts neurons and studied the impact on fluid intake, fluid preference and feeding. Activation of LHA Nts neurons stimulated drinking in water-replete and dehydrated mice, indicating that these neurons are sufficient to promote water intake regardless of homeostatic need. Interestingly, mice with activated LHA Nts neurons drank any fluid that was provided regardless of its palatability, but if given a choice they preferred water or palatable solutions over unpalatable (quinine) or dehydrating (hypertonic saline) solutions. Notably, acute activation of LHA Nts neurons robustly promoted fluid but not food intake. Overall, our study confirms that activation of LHA Nts neurons is sufficient to induce drinking behavior and biases for fluid intake. Hence, LHA Nts neurons may be important targets for orchestrating the appropriate ingestive behavior necessary to maintain fluid homeostasis. This article is part of the Special Issue entitled ‘Hypothalamic Control of Homeostasis’. •Activation of LHA Nts neurons is sufficient to promote voracious drinking.•Activation of the LHA Nts neurons biases for fluid consumption over food intake.•LHA Nts neuronal activation induces drinking of any provided liquid.•LHA Nts neuron-activated mice prefer water over dehydrating or unpalatable liquids.•LHA Nts neuron-activated mice prefer palatable liquids over water.