PhD defense thesis Anna Athanassi "L’impact du stress précoce sur la perception hédonique des odeurs et ses bases neurales chez la souris"

Anna Athanassi, Doctorante NEUROPOP

A l'invitation de

Anna Athanassi, Doctorante NEUROPOP

Anna Athanassi

J’ai le plaisir de vous inviter à ma soutenance de thèse intitulée "L’impact du stress précoce sur la perception hédonique des odeurs et ses bases neurales chez la souris". Elle sera présentée en français.

Vous trouverez en pièces jointes le résumé de la thèse en français et en anglais.

 

Le jury sera composé de 

Dr Claire Martin, CNRS Paris (rapportrice) 
Dr Jean Christophe Sandoz, CNRS Paris Saclay (rapporteur) 
Dr Sylvain Delplanque, Université de Genève (examinateur) 
Dr Gabriel Lepousez, Institut Pasteur Paris (examinateur) 
Dr Marion Richard, Université Claude Bernard Lyon 1 (examinatrice) 
Dr Nathalie Mandairon, CNRS Lyon (directrice de thèse) 
Dr Sebastian Fernandez, Université de Nice (invité)

 

Pour celles et ceux qui ne pourraient pas assister en présentiel, un lien Zoom est également prévu :
https://cnrs.zoom.us/j/93588448188?pwd=lght9WWjeoycA54d939xCvTyuI0KVC.1
 

Abstract

Childhood maltreatment can lead to depressive states in adulthood. Neglect, abuse, and any form of early-life stress can disrupt brain development, affecting emotional balance into adulthood. Additionally, depression is often associated with disturbances in odor perception. Odors play a crucial role in many vital behaviors, such as eating, social interactions, and avoiding danger. Therefore, any alteration in olfactory perception, particularly of pleasant odorants, may reduce daily pleasures and exacerbate depressive symptoms. In this context, my thesis aims to investigate how early-life stress affects the perception of pleasant odorants in adulthood, and seeks to uncover the neural mechanisms underlying these alterations.
To do so, I used a murine model of early stress induced by limited nesting and bedding, which confirmed an alteration in emotional behavior in adulthood, but also revealed a disturbance in the perception of pleasant odorants (STUDY 1). We then explored the mechanisms of this olfactory impairment by focusing first on the interneurons of the olfactory bulb, whose role in encoding the hedonic value of odorants has been previously demonstrated. These interneurons, generated postnatally (P0-P1), are in their critical integration period during the early stress phase and are therefore particularly vulnerable. Our observations show that early stress alters the fine morphology of interneurons specifically responsive to pleasant odorants. Olfactory bulb interneurons are also the targets of adult neurogenesis. We demonstrated that the new neurons, although born long after the stress period, have altered survival and plasticity. All these disturbances lead to an overall modification of the neural activity of the olfactory bulb in response to pleasant odorants, disrupting the output signal of this structure. Two other brain structures involved in encoding the hedonic value of odorants, the olfactory tubercle and the ventral tegmental area, are also affected. These structures are part of the reward circuit and are particularly active during approach behavior toward pleasant odorants. We revealed that their activity in response to pleasant odorants is altered in animals subjected to early stress.
Finally, the fact that pleasant odorants can induce motivated behavior, engaging the reward circuit, suggests dopamine release, a key molecule in this circuit. To directly study dopamine release in response to odors, I established the fiber photometry technique coupled with video signal analysis in the laboratory (STUDY 2). My initial analyses show an increase in dopamine in response to attractive odors compared to non-attractive odorants. The analysis of the effects of early stress on this mechanism is currently ongoing.
In conclusion, our results indicate that early stress modifies the neural substrates responsible for the perception of pleasant odorants, which has implications for understanding resilience to anhedonia,or the loss of interest and motivation for pleasant stimuli, and for assessing the severity of depressive symptoms in individuals with a history of early stress.

Team
13 December 2024 14:00–17:00

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