The Agouti-related peptide (AgRP) neurons are hunger signalling neurons activated during hunger and suppressed during satiety through neuroendocrine feedback. However, increasing evidence shows the suppression of AgRP activity can occur prior to calorie consumption on a timescale that is inconsistent with neuroendocrine feedback. This highlights an important, yet poorly defined, role of synaptic input from sensory information on the control of AgRP neurons.
Olfaction, or the sense of smell, is a predictive sense gated by the olfactory bulb (OB). Extensive observations including olfactory impairment reported in obese patients, and heightened olfactory processing during hunger, suggests a link between olfaction and metabolism. Recently our lab showed that the deletion of the ghrelin receptor in the OB led to impaired olfactory sensitivity and metabolism, especially during hunger. This evidence highlights the reciprocal relationship between olfaction and metabolism, leading us to hypothesize that the olfactory system may convey important sensory cues of food availability to AgRP neurons.
In this study, we used fiber photometry to record AgRP neuronal activity in free-moving AgRP-cre mice with or without olfactory impairment during a sequential odour presentation task under either fast or fed condition. Analysis showed sniffing directly underneath the odour ports transiently inhibited AgRP activity in normal mice. Interestingly, olfactory impairment attenuated the odour mediated AgRP inhibition only in fed but no fasted mice. Therefore, our results provided preliminary evidence that the olfactory system influences AgRP activity in a metabolic state dependent manner.