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Lateral hypothalamic neurotensin-expressing neurons shape the balance between drinking, feeding and socializing

Chantal Wissing1, Anne Petzold2, Hanna van den Munkhof2, Tatiana Korotkova2

1 Institute for Systems Physiology, University of Cologne, Cologne, Germany
2 Institute for Systems Physiology, Max Planck Institute for Metabolism Research, Cologne, GermanyUniversity of Cologne, Cologne, Germany,

In the lateral hypothalamus (LH), distinct cell populations modulate innate behaviours. We investigated the role of neurotensin-expressing (Nts) neurons in the LH in balancing feeding, drinking, and social behaviour across internal states. In vivo calcium imaging in freely behaving mice revealed distinct activity patterns of Nts-LH neurons associated with water and food stimuli. After prolonged food restriction, water responses were strongly enhanced, suggesting that Nts-LH neurons are involved in maintaining water intake during hunger pressure. Activation of Nts-LH neurons counteracted hunger pressure by promoting water intake and rapidly increasing water consumption. Nts-LH neurons also responded to social stimuli, preferentially to unfamiliar conspecifics. Activation of these neurons increased exploration of food and decreased exploration of the unfamiliar conspecific. During a choice between a familiar and an unfamiliar conspecific, activation of Nts-LH neurons decreased social exploration of the unfamiliar conspecific. These findings suggest that Nts-LH neurons are implicated in the encoding and recognition of social cues. We identified projections of Nts-LH neurons in the anteroventral and anteromedial thalamic nuclei, linked to spatial attention and navigation. Activation of these inputs improved navigation to and engagement with water or food without affecting consumption itself. In contrast, social approach was not affected by the activation. Our results suggest that Nts-LH neurons regulate internal states and the trade-off between drinking and other innate behaviours by guiding spatial attention. We gratefully acknowledge support by the ERC Consolidator Grant (772994, FeedHypNet,  T.K.) and DFG (Project-ID 431549029 – SFB 1451  T.K., EXC2030 CECAD  T.K.,  EXC 2030 – 390661388,  A.P.).