Investigating the role of centrifugal hypothalamic projections to the olfactory system in feeding behaviour.

Feeding and olfaction are tightly interconnected. While feeding relies on olfactory-driven behaviour, olfaction is also reciprocally modulated by the nutritional status. Starvation notably enhances olfactory sensitivity and olfactory-driven behaviours to optimize foraging for food. Although the hunger state-dependent regulation of olfaction is a fundamental mechanism conserved across phylae, its underpinning mechanisms remain unclear. Here, we propose to study the specific involvement of long-range centrifugal projections to early and higher olfactory processing centres from the hypothalamus — a pivotal node for feeding regulation — in the modulation of olfaction and feeding behaviour in mice. The overarching aim of this innovative proposal is, therefore, to unravel the role of hypothalamic centrifugal projections to the olfactory system at the anatomical, physiological and behavioural levels. In TP4, we propose to employ a complementary set of approaches including chemogenetics, optogenetics and two-photon calcium imaging in concert with feeding and olfactory behavioural tests with the intent to provide novel mechanistic insights into the hunger state-dependent regulation of olfaction and its effect on feeding behaviour.