ROLE OF LATERAL HYPOTHALAMIC SUBPOPULATIONS IN FOOD-RELATED MEMORY FORMATION

We live in a world that is highly conducive to eating – with high food palatability, easy food availability, and omnipresence of food cues – leading to increased caloric intake, weight gain and associated health disorders. The identification of anorectic mechanisms is of paramount importance for public health. Eating behaviour is regulated through neurochemically distinct neural subpopulations of the lateral hypothalamus (LH). In this study, we focused on an LH subpopulation that secretes the neurotrophin brain-derived neurotrophic factor (BDNF). Using single-cell Ca²⁺ imaging in freely moving mice with free access to nutritional and social rewards, we show that BDNF^LH neurons are excited by food more than by any other rewards. The prevalence of food-encoding among BDNF^LH neurons increased with experience. BDNF^LH neurons robustly respond to slow post-prandial peripheral hormones such as leptin and fast post-prandial metabolites such as glucose. Chemogenetic activation of BDNF^LH neurons in freely behaving mice during the consolidation of food memories led to memory overgeneralisation across feeding contexts. Overall, our findings suggest an important role of BDNF^LH neurons in the experience- and state-dependent adaptation of eating behaviour. Thereby, we provide an entry point for the identification of neural mechanisms that shape eating patterns and that could potentially be harnessed to limit food overconsumption in the modern obesogenic environment.