Our goal is to investigate how the olfactory system evolves during development and neurogenesis as well as under the influence of the odorant environment and internal metabolic signals. We are using rodents as our main experimental model. We are investigating different levels of modulation, from olfactory receptors to central areas of the brain. We develop molecular, cellular, anatomical and physiological techniques as well as behavioral assays.

Our main research topics:

Theme 1 : Functional properties of olfactory receptors and olfactory sensory neurons:

In this topic, we are investigating the membrane properties of olfactory sensory neurons (OSNs) as well as properties of olfactory receptors’ (ORs). We use molecular electrophysiology (patch-clamp) and in vitro approaches. For instance we are focusing on the responses of OSNs and ORs to odorant mixtures. We are using gene-targeted mice in which the fluorescent protein GFP is expressed under the promoter of ORs with a wide spectrum (SR1, olfr15) or with a narrow spectrum (MOR23, M71). Using patch-clamp, we can characterize the responses of these neurons to single odorant molecules or odorant molecules in a mix. We also express ORs in heterologous systems in order to evaluate their intrinsic properties through functional tests.
We are also interested in the functional properties and role of olfactory neurons during development of the olfactory system. This project is developed in collaboration with the laboratory of Peter Mombaerts, Max Planck Research Unit for Neurogenetics, Frankfurt, Germany. Our aim is to better understand how olfactory receptors are involved in the addressing of axons during neurogenesis. To this end, using gene-targeted mice, we replace the expression of the olfactory receptor with another G protein-coupled receptor (GPCR), such as beta-adrenergic receptor. In Dijon, we then characterize the membrane properties of these OSNs expressing the other type of GPCR using patch clamp (Omura et al, 2014).

Theme 2 : Odorant induced plasticity in olfactory neurons

Our goal is to understand the consequences of the odorant environment on the properties of olfactory neurons. After exposure to odorant molecules we measure the anatomical, molecular and physiological effects on neuronal populations labeled with GFP. We observed that during post-natal development, exposure to their cognate ligand induced plasticity on certain populations of neurons (Cadiou, Aoude et al, 2014). We are currently investigating the consequences on the properties of OSNs of the odorant exposure during adulthood or during embryonic development. We also investigated the anatomical and molecular effects of sensory deprivation during the postnatal development. We observed that unilateral naris closure induced different effects on different OSNs’ populations (Molinas et al, 2016).

Theme 3 : Plasticity of the olfactory system induced by homeostatic changes: effects of nutritional status and diet.

The objective of this project is to evaluate the effects of diet on the physiology of the olfactory system (peripheral and central levels) and olfactory behaviors. We use two types of diet inducing metabolic disorders: a high fructose diet rapidly inducing diabetes, and a high fat high sugar inducing both diabetes and obesity. We assess the impact of these diets i) on the physiology of the olfactory epithelium using electrophysiology (EOG and patch-clamp), molecular biology and immunohistochemistry; ii) on the status of the OSNs’ projections into the olfactory bulb by immunohistochemistry and on the functional properties of the olfactory bulb using c-fos labelling; iii) the olfactory behavior by basic tests (habituation / dishabituation, buried food, plethysmography).

Theme 4 : Neural structures involved in olfactory, hedonic and feeding behaviors: connections, plasticity and behavioral impact.

Olfaction plays a key role in the hedonic component of feeding behavior. On one hand, some odors, considered as highly appetitive, trigger food intake; on the other hand, through specific sensory satiation, there is a gradual reduction of food-elicited pleasure during food consumption. The neural correlates of these phenomena remain unknown. To address this challenge, it is required to describe the connectome between the central structures integrating olfactory, homeostatic (hypothalamus ...) and reward (ventral tegmental area ...) informations. We use stereotactic injections of retrograde tracers such as polysynaptic virus (PRV) and monosynaptic cholera toxin (CTb). Double-immunocytochemical characterization of the retrogradely labeled neurons is also performed. The functional significance of the identified circuits might be investigated using behavioural paradigms.