Expression of feeding-related neuromodulatory signalling molecules in the mouse central olfactory system

Abstract

Various neural systems cooperate in feeding behaviour, and olfaction plays crucial roles in detecting and evaluating food objects. While odour-mediated feeding behaviour is highly adaptive and influenced by metabolic state, hedonic cues and learning processes, the underlying mechanism is not well understood. Feeding behaviour is regulated by orexigenic and anorexigenic neuromodulatory molecules. However, knowledge of their roles especially in higher olfactory areas is limited. Given the potentiation of feeding behaviour in hunger state, we systemically examined the expression of feeding-related neuromodulatory molecules in food-restricted mice through quantitative PCR, in the olfactory bulb (OB), olfactory tubercle (OT), and remaining olfactory cortical area (OC). The OT was further divided into attraction-related anteromedial, aversion-related lateral and remaining central regions. Examination of 23 molecules including neuropeptides, opioids, cannabinoids, and their receptors as well as signalling molecules showed that they had different expression patterns, with many showing elevated expression in the OT, especially in the anteromedial and central OT. Further, in mice trained with odour-food association, the expression was significantly altered and the increase or decrease of a given molecule varied among areas. These results suggest that different olfactory areas are regulated separately by feeding-related molecules, which contributes to the adaptive regulation of feeding behaviour.

Hypothetical Roles of the Olfactory Tubercle in Odor-Guided Eating Behavior

“…Indeed, the expression levels of the orexigenic peptide (ghrelin) and receptors (cannabinoid receptor 1, opioid receptor delta 1, and opioid receptor kappa 1) were increased in the anteromedial OT by odor-guided food-seeking behavior. A similar increase was noted in the levels of the anorexigenic peptide (argininevasopressin) and receptors (leptin receptor and melanocortin four receptor) in the anteromedial OT (Nogi et al, 2020). Celltype identification will assist in determining how specific neural circuits in the OT function in eating behaviors by elucidating which neurons (D1 receptor or D2 receptor-expressing neurons and other types of neurons) express the aforementioned peptides and receptors.…”

“…In the anteromedial OT, various orexigenic peptides (orexin and prodynorphin) and receptors (orexin receptors 1 and 2, ghrelin receptor, and opioid receptor kappa 1) were highly expressed compared to those in the lateral OT. This trend was also seen in anorexigenic peptides (CART peptide) and receptors (melanocortin four receptor and arginine-vasopressin receptor 1a) (Nogi et al, 2020). Odor cues may influence the release and expression of these feeding-related peptides and receptors in the anteromedial OT and the subsequent ingestive behaviors.…”

“…In contrast, D2 receptor-expressing neurons in the anteromedial domain and D1 receptor-expressing neurons in the lateral domain may suppress eating by low evaluation, demotivation, and disgusting response to food-related odors and flavors. The OT also expresses orexigenic and anorexigenic peptides and their receptors ( Cansler et al, 2020 ; Nogi et al, 2020 ), which may endow OT domains with homeostatic control over odor-guided eating behaviors ( Aime et al, 2007 ; Palouzier-Paulignan et al, 2012 ). For instance, hunger state and its orexigenic hormonal signals such as orexin and ghrelin might upregulate the responses of D1 receptor-expressing neurons in the anteromedial OT to food odors and flavors, resulting in increase of food intake.…”

The conserved endocannabinoid anandamide modulates olfactory sensitivity to induce hedonic feeding in C. elegans

“…Both AEA and 2-AG amplify the response of primary chemosensory cells, such as the sweet-taste cells in the tongue (Yoshida et al, 2010, 2013), which may help to explain increased consumption of sweet foods and liquids. Cannabinoids can also increase the sensitivity of the mammalian olfactory system as measured during food-odor exploration (Heinbockel & Straiker, 2021; Nogi et al, 2020; Soria-Gómez et al, 2014). We observed an analogous effect in C. elegans , in that AEA alters the sensitivity of a primary chemosensory neuron, AWC.…”

The metabolic status and olfactory function

“…For fifty years, numerous efforts have been done to localize hormones/peptides and their receptors by immunohistochemistry, radioimmunoassay, radioactive, or not, hormone binding assays and more recently molecular biology. The demonstration that most metabolic anorexigenic and orexigenic hormones and peptides receptors traditionally considered to be feeding related are expressed in the olfactory system in many species strongly came to support the findings that odour processing can be modulated by the nutritional status; this especially in the first two levels of the olfactory system, the olfactory mucosa (OM) and the olfactory bulb (OB), thus well before the involvement of cortical integration (Lucero, 2013;AlKoborssy et al, 2014;Nogi et al, 2020).…”