Deciphering olfactory bulb circuits modulated by metabolic signals

Sensory Signals (The Royal College of Physicians, London, UK) (2022) Proc Physiol Soc 50, C15

Poster Communications: Deciphering olfactory bulb circuits modulated by metabolic signals

Merve Oncul1, Jamie Johnston1

1School of Biomedical Sciences, Faculty of Biological Sciences, University of Leeds, Leeds, United Kingdom

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Olfaction is important for the regulation of food intake and energy homeostasis and contributes to food choice and its consumption. Olfactory processing is influenced by the feeding status, satiety decreases and fasting increases olfactory acuity. Consistent with this, olfaction is modulated by changing levels of several metabolically regulated molecules such as insulin and glucose. Insulin is a key hormone for feeding, energy metabolism and cognition. The olfactory bulb has the highest density of insulin receptors in the brain. Previous studies have demonstrated the action of insulin on the mitral cells which are projection neurons of the olfactory bulb. Insulin increases the excitability of mitral cells by inhibiting a voltage-gated potassium channel (Fadool et al. 2004, 2011). However, it has not been fully characterized how insulin acts on the cells in the glomerular layer which are initial sites for odour information processing in the olfactory bulb. Here, we investigate how olfactory bulb circuits are regulated by metabolic signals and the role of these molecules on olfactory perception and feeding behaviour. Especially, we are investigating mechanisms underlying the role of insulin in the modulation of olfaction and identifying cellular targets of insulin in the mouse olfactory bulb. To explore these mechanisms, we are using variety of approaches including patch-clamp electrophysiology, 2-photon calcium imaging, immunohistochemistry and behavioural tests. We perform voltage clamp recordings from acute mouse olfactory bulb slices to test the effect of insulin on potassium currents in the glomerular layer. Our electrophysiology experiments demonstrate an effect of insulin on the cells in the glomerular layer; a subset show strong suppression of a voltage-gated potassium current. Following bath application of insulin (172 nM), current suppression was observed in 6 of 13 recorded cells from 11 mice. We use genetically encoded Ca indicators and 2-photon imaging to test action of insulin at the circuit level and our preliminary results from 3 mice suggest that insulin modulates olfactory-nerve evoked responses. We perform immunostaining to show the distribution of insulin receptors in the olfactory bulb and behavioural analyses to test olfactory sensitivity depending on the feeding state. Overall, this study will help to gain insight into the role of insulin in olfactory information processing by nutritional state and how this regulates olfactory-driven behaviour in mice.
 



Where applicable, experiments conform with Society ethical requirements.

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