Description du sujet de thèse

Neurobiological mechanisms of post-stress recovery: from respiration to brain circuits
Background:
The project is based on an aversive U-Maze that reveals two physiologically distinct immobility states, identified during conditioning by immobility (accelerometer) combined with a respiratory frequency threshold at 4–6 Hz and elevated heart rate, and a "recovery" state with slow respiration at 2–4 Hz and reduced heart rate, whose expression is associated with post-task markers compatible with a lower stress load.
The thesis will test how this recovery state is expressed (i) at the level of stress/valence systems (PVN-CRH, dopamine) and (ii) via a respiration–olfactory bulb–PFC loop that may control/stabilize pro-defensive vs. restorative neuronal states.

Objectives:
- Measure in real time the activity of CRH neurons in the PVN (GCaMP8f in CRH-Cre) and dopaminergic signals (GRAB-DA1h in target regions) during "threat" vs. "recovery" episodes in a U-Maze.
- Test the involvement of respiratory oscillations via the olfactory bulb by disrupting/imposing rhythms (e.g., 13 Hz for disruption, 2–4 Hz or 4–6 Hz; open-loop/closed-loop and optogenetic approaches) and assessing the impact on immobility states and neurophysiological signatures.
- Relate these measurements to "stress" outputs (post-task corticosterone, Elevated Plus Maze, and composite index based on thigmotaxis, sleep fragmentation, REM reduction, and heart rate).

Experimental approach
Mice are instrumented for respiration (nasal pressure sensor), autonomic activity (ECG/HRV) and, depending on sub-projects, LFP OB/PFC, with addition of optical fiber(s) for photometry after viral expression of GCaMP8f/GRAB-DA1h.
The U-Maze includes conditioning phases to robustly sample both states, followed by post-task measurements (corticosterone, EPM) and sleep recordings to compute the stress score.

Expected results:
The central expectation is to determine whether slow-breathing "recovery" is accompanied by decreased PVN-CRH activity and dopaminergic dynamics compatible with a "relief/recovery" process, and whether these signatures are causally modulated by manipulation of olfactory bulb → PFC oscillations. This framework should produce a mechanistic model linking a behavioral/physiological biomarker (slow breathing in safe zone) to neurobiological mechanisms of post-stress recovery, beyond mere absence of stress.

Contexte de travail

The position is based in the Brain Plasticity Laboratory (CNRS UMR 8249), hosted at the École Supérieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris - PSL), located at 10 rue Vauquelin, 75005 Paris. The laboratory conducts research in neuroscience, with a focus on brain plasticity mechanisms, stress-sleep interactions, and the use of technologies in neurophysiology and behavior. The candidate will join a dynamic and multidisciplinary team, benefiting from a high-level research environment within PSL University, and will have access to technical platforms including an accredited animal facility and electrophysiology and fiber photometry equipment. The PhD student will have an individual office and dedicated computers for office work and data analysis. All means necessary for the successful completion of the project will be provided.

Contraintes et risques

The project requires obtaining level 1 experimenter certification. The PhD student will be required to perform surgical procedures under supervision initially (implantations of optical fibers, electrodes), as well as manipulations of viral vectors in a L2 containment laboratory. Regulatory certification in surgery will be necessary. Monitoring behavioral protocols and physiological recordings requires schedule flexibility and may require occasional presence outside standard hours. The candidate must strictly respect animal ethics rules and safety protocols in force. Sensitivity to animal welfare and the ability to work rigorously and methodically are essential.