Odor-Induced Neuronal Rhythms in the Olfactory Bulb Are Profoundly Modified in ob/ob Obese Mice.

Yan Chelminski,Claire Martin,Serge H Luquet,Amandine Everard,Nicolas Meunier,Christophe Magnan,Hirac Gurden

doi:10.3389/fphys.2017.00002

Abstract

Leptin, the product of the Ob(Lep) gene, is a peptide hormone that plays a major role in maintaining the balance between food intake and energy expenditure. In the brain, leptin receptors are expressed by hypothalamic cells but also in the olfactory bulb, the first central structure coding for odors, suggesting a precise function of this hormone in odor-evoked activities. Although olfaction plays a key role in feeding behavior, the ability of the olfactory bulb to integrate the energy-related signal leptin is still missing. Therefore, we studied the fate of odor-induced activity in the olfactory bulb in the genetic context of leptin deficiency using the obese ob/ob mice. By means of an odor discrimination task with concomitant local field potential recordings, we showed that ob/ob mice perform better than wild-type (WT) mice in the early stage of the task. This behavioral gain of function was associated in parallel with profound changes in neuronal oscillations in the olfactory bulb. The distribution of the peaks in the gamma frequency range was shifted toward higher frequencies in ob/ob mice compared to WT mice before learning. More notably, beta oscillatory activity, which has been shown previously to be correlated with olfactory discrimination learning, was longer and stronger in expert ob/ob mice after learning. Since oscillations in the olfactory bulb emerge from mitral to granule cell interactions, our results suggest that cellular dynamics in the olfactory bulb are deeply modified in ob/ob mice in the context of olfactory learning.

Highlights

Dysregulation in the control of food intake is a major contributor to the rising number of obese people and strongly contributes to the obesity epidemic related lethal complications such as cardiovascular diseases and type 2 diabetes (Dietrich and Horvath, 2012)
It was observed that neurons elsewhere in the brain (Hayes et al, 2010), including the olfactory bulb (OB), the first location in the brain to perform a spatiotemporal coding of odors, express significant amounts of leptin receptors (Shioda et al, 1998; Prud’homme et al, 2009)
We challenged ob/ob mice (n = 14) and matched WT mice (n = 18) on an odor discrimination task based on the acquisition of a Go/No-Go task (Figure 1A)

Summary

Introduction

Dysregulation in the control of food intake is a major contributor to the rising number of obese people and strongly contributes to the obesity epidemic related lethal complications such as cardiovascular diseases and type 2 diabetes (Dietrich and Horvath, 2012). A fine tuning of feeding behavior is made possible by the central integration of peripheral energy-related circulating signals released at the periphery of the brain (Luquet and Magnan, 2009). Among these hormones, leptin is a known anorectic signal mainly expressed by the adipose tissue according to energy store (Zhang et al, 1994; Friedman and Halaas, 1998). Odor Processing in ob/ob Mice of the leptin signaling pathway invariably leads to hyperphagia, obesity, and corollary disease in both human and rodents (Schwartz and Porte, 2005). It was observed that neurons elsewhere in the brain (Hayes et al, 2010), including the olfactory bulb (OB), the first location in the brain to perform a spatiotemporal coding of odors, express significant amounts of leptin receptors (Shioda et al, 1998; Prud’homme et al, 2009)

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Results

Conclusion