Abstract / Summary
Enhanced excitability of output neurons in the olfactory bulb (OB) has been linked to regulation of energy homeostasis. The mechanism by which the olfactory system can drive metabolic state while processing odor information remains elusive yet must depend upon integration and relay to the rest of the brain. Herein, we screened brain-wide neuronal ensembles that preferentially engaged during odor stimulation (referred to as ODORTRAP) utilizing FOSTRAP activity mapping. Mice were exposed to the odor isopropyl tiglate (IPT), a preferred ligand for the olfactory receptor 160, previously shown to be vulnerable to diet-induced obesity. Odor activation resulted in elevated labelling in the olfactory bulb (ODORTRAP) (p < 0.001), as well as in higher olfactory cortices including anterior olfactory nucleus, piriform cortex, and cortical amygdala (p < 0.05). Interestingly, IPT differentially recruited hypothalamic feeding areas, namely the arcuate (ARC), dorsomedial (DMH) and lateral (LH) hypothalamus (p < 0.001), while the ventromedial hypothalamic nucleus and the suprachiasmatic nucleus exhibited no change in ODORTRAP activity (p > 0.05). In mice that were maintained on moderately high-fat (MHF) diets, we discovered that obesity re-models the activation pattern across the brain. Obese mice exhibited loss of ODORTRAP activity in the ARC (p < 0.0001), whereas in the DMH and LH increased baseline activity that obscured any odor-linked neural activity. While IPT activated the nucleus accumbens and medial septum in control mice (p < 0.01), obese mice demonstrated no changes in ODORTRAP activity (p > 0.05). Our study identifies key brain regions linking chemosensation and metabolic state, specifically demonstrating alteration in activity in hypothalamic domains upon obesogenic diet.