Thesis – Nesrine MERABET

Acute hypercapnic stress modulation of nocifensive behavior and aversive value coding

Jury

• Lisa SCHEUNEMANN, Research scientist, University of Berlin – Reviewer
• Guillaume ISABEL, Professor, CBI, Toulouse – Reviewer
• Sarah MONDOLINI, Research scientist, INMED, Marseille – Examiner
• Hervé CADIOU, Associate Professor, INCI, Strasbourg – Examiner
• Michel VIGNES, Professor, IBMM, University of Montpellier – Examiner
• Emmanuel PERISSE, Research scientist, IGF, University of Montpellier – Thesis supervisor

Summary

Survival depends on avoiding threats, a process shaped by experience and internal states. Notably, acute stress can induce analgesia, yet the neural mechanisms by which stress alters aversive value coding remain unclear. Using Drosophila, we show that prior noxious experience induces intensity-dependent analgesia and triggers the release of CO₂​, a known stress signal. Surprisingly, this effect is mediated by tracheal dendrite (td) neurons in the respiratory system rather than classic olfactory pathways. We then demonstrated that activation of td neurons induces analgesia, whereas their inhibition suppresses it and restores normal nocifensive and learned behavior. Finally, high CO₂​ exposure decreases dopaminergic neuron responses to electric shocks, thereby impairing aversive memory formation. Together, we propose that under hypercapnic (high CO₂) stress, td neurons modulate nociceptive computation and aversive value coding in the brain to facilitate appropriate naïve and learned behavioral responses.