Time to Drink: Activating Lateral Hypothalamic Area Neurotensin Neurons Promotes Intake of Fluid over Food in a Time-Dependent Manner

The lateral hypothalamic area (LHA) is essential for ingestive behavior but has primarily been studied in modulating feeding, with comparatively scant attention on drinking. This is partly because most LHA neurons simultaneously promote feeding and drinking, suggesting that ingestive behaviors track together. A notable exception are LHA neurons expressing neurotensin (LHA(Nts) neurons): activating these neurons promotes water intake but modestly restrains feeding. Here we investigated the connectivity of LHA(Nts) neurons, their necessity and sufficiency for drinking and feeding, and how timing and resource availability influence their modulation of these behaviors. LHA(Nts) neurons project broadly throughout the brain, including to the lateral preoptic area (LPO), a brain region implicated in modulating drinking behavior. LHA(Nts) neurons also receive inputs from brain regions implicated in sensing hydration and energy status. While activation of LHA(Nts) neurons is not required to maintain homeostatic water or food intake, it selectively promotes drinking during the light cycle, when ingestive drive is low. Activating LHA(Nts) neurons during this period also increases willingness to work for water or palatable fluids, regardless of their caloric content. By contrast, LHA(Nts) neuronal activation during the dark cycle does not promote drinking, but suppresses feeding during this time. Finally, we demonstrate that the activation of the LHA(Nts) -> LPO projection is sufficient to mediate drinking behavior, but does not suppress feeding as observed after generally activating all LHA(Nts) neurons. Overall, our work suggests how and when LHA(Nts) neurons oppositely modulate ingestive behaviors