Identification of a neural network for oxytocinergic amplification of respiratory sinus arrhythmia: implication in calming behaviors

Julie Buron

Perinatal Imprintings ans Neurodevelopmental Discorders Team

Abstract
Respiratory sinus arrhythmia (RSA) refers to oscillations in heart rate in phase with respiration: the heart rate increases during inspiration and decreases during expiration. RSA amplitude is used in the clinic as a marker of health because a high RSA amplitude is physiologically and psychologically beneficial. Relaxation and positive socio-emotional states can amplify RSA but the mechanisms are not well understood. This thesis project identifies the neural network by which oxytocin, a neurohormone known to positively influence individuals’ health, amplifies RSA during calming behavior. We recorded respiratory and cardiac activities, and their neuronal commands, in mice in vivo, on reduced preparations and on brainstem slices. We combined these models with optogenetics, chemogenetics, electrophysiology and viral tracing. This work identifies a new pathway for RSA amplification: oxytocin, released by hypothalamic oxytocinergic neurons that project to the brainstem, modulates neuronal connectivity within cardiorespiratory nuclei and leads to an amplification of the respiratory modulation of cardiac parasympathetic activity, which amplifies RSA. We also showed that oxytocinergic neurons participate in the RSA amplification during stress recovery in adult mice. This work shows how a central action of OT induces physiologically beneficial regulation of cardiac activity during calming behavior, which could lead to therapeutic strategies for anxiety disorders and coping with stress.

Jury
Dr Gilles Fortin, rapporteur – Institut de biologie de l’ENS (IBENS), Paris
Pr Olivier Baud, rapporteur – Hôpitaux Universitaire de Genève (Service de néonatalogie)
Dr Muriel Thoby-Brisson, examinatrice – Institut de Neurosciences Cognitives et Intégratives d’Aquitaine (INCIA), Bordeaux
Pr Laurence Bodineau, examinatrice – UMR_S1158 (Neurophysiologie respiratoire expérimentale et clinique), Paris
Dr Jean-Christophe Roux, Président du jury – Faculté de médecine de la Timone (Marseille Medical Genetics)
Dr Françoise Muscatelli, directrice de thèse – Inmed, Marseille
Dr Clément Menuet, co-directeur de thèse – Inmed Marseille

Thursday, September 28, 2023 at 2pm, Inmed conference room