Exploration des mécanismes centraux du couplage respiratoire-cardiovasculaire :
Rôle des neurones GABAergiques du complexe de pré-Bötzinger et modulation par les corps carotidiens et l’ocytocine
Ambre Linossier
Team “Perinatal Imprintings and Neurodevelopmental Disorders”

Abstract
The survival of organisms relies on maintaining the balance of essential physiological constants, including blood gas concentration. This regulation is ensured by the respiratory and cardiovascular systems, whose physiological efficiency is maximized by the respiratory-cardiovascular coupling (RCC). RCC has a primarily central origin, through interactions between respiratory neurons and autonomic cardiovascular neurons located in the brainstem which generate oscillations in heart rate and blood pressure in phase with respiration. However, the central mechanisms underlying these oscillations remain poorly characterized. The aim of my thesis was to study the neuronal interactions and the mechanisms underlying RCC by combining anatomo-functional approaches, including viral tracing and optogenetics. This work first demonstrated that GABAergic neurons of the pre-Bötzinger complex, the neuronal group generating the inspiratory rhythm, contact key regions for RCC and play a role in its establishment under basal conditions. Moreover, RCC can be modulated under various physiopathological conditions. Notably, it is enhanced in positive social contexts and a study conducted at the beginning of my thesis helped show that oxytocin potentiates the cardiac aspect of RCC by modulating glycinergic neurons of the pre-Bötzinger complex. Conversely, RCC is altered in certain pathologies such as hypertension or sleep apnea. Using a protocol of repeated stimulations of the carotid bodies, I demonstrated that these peripheral organs contribute to the establishment of RCC exacerbation. In summary, my work contributes to a better understanding of the central mechanisms of RCC by highlighting the crucial role of GABAergic neurons in the pre-Bötzinger complex and by identifying two mechanisms of RCC modulation: a central physiological one, via oxytocin, and a peripheral one via the carotid bodies, with potential pathological consequences.

Jury
Gilles FORTIN, Président – IBENS, Paris
Muriel THOBY-BRISSON, Rapportrice – INCIA, Bordeaux
Baptise BALANCA, Rapporteur – Hôpital Pierre Wertheimer – CRNL, Bron
Nathalie BUONVISO, Examinatrice – CRNL, Bron
Pascale QUILICHINI, Examinatrice – INS, Marseille
Christian Gestreau, Co-directeur de thèse – INMED, Marseille
Clément Menuet, Co-directeur de thèse – INMED, Marseille

Friday 13 June 2025 at 2pm – Inmed conference room