LATERAL HYPOTHALAMIC NEUROTENSIN-EXPRESSING NEURONS REGULATE THE PRIORITIZATION OF DRINKING, FEEDING AND SOCIALIZING

Neuronal populations within the lateral hypothalamus (LH) play essential roles in coordinating motivational drives and guiding adaptive behaviors. Neurotensin-expressing LH (Nts-LH) neurons have emerged as important integrators of internal state signals and external sensory cues. Here, we combined in vivo calcium imaging, circuit mapping, and optogenetic manipulations to investigate how Nts-LH neurons regulate competing behaviors related to feeding, drinking, and social interaction.
Nts-LH neurons displayed distinct activity patterns during approach and consumption of food and water, and their responses dynamically shifted with hunger state, indicating a role in balancing hydration and energy needs under metabolic pressure. Activation of Nts-LH neurons promoted water intake and modestly increased feeding, biasing behavior toward hydration when animals were hungry. These neurons also encoded socially relevant stimuli, responding preferentially to unfamiliar conspecifics, and their activation reduced social exploration, suggesting context-dependent modulation of social behavior.
Anterograde tracing and optogenetic stimulation revealed that Nts-LH projections to anterior thalamic regions support the integration of motivational drive with spatially directed foraging. Stimulation of this pathway enhanced responsiveness to food-predictive cues, navigation toward food sources, and influenced the prioritization of social versus feeding behaviors depending on internal state and resource availability.
Together, these findings demonstrate that Nts-LH neurons form a multifunctional circuit that coordinates survival-related behaviors by integrating hunger, hydration, and social context. This work provides a unifying framework for understanding how the LH contributes to adaptive decision-making when animals face competing motivational demands.
We gratefully acknowledge support by the ERC consolidator grant HypFeedNet, DFG-CRC1451 (to TK, AP) and EXC2030-CECAD.