Venue: BBS
Defense in french
Vianney Salvi
Team: Mococo
INCIA
Title
The pupillary evoked response: a study of the cingulo-coeruleus pathways in rodents and humans
Abstract
The organization of the cingulate cortex (CC) has been the subject of intensive studies, highlighting its central role in motor control, cognition, and arousal regulation. One key anatomical pathway through which the CC influences behavior is its efferent connection to the locus coeruleus (LC), a brainstem nucleus responsible for cortical noradrenaline (NA) release. Despite this anatomical link, the functional organization of CC subregions in modulating LC-NA activity remains largely unexplored. This thesis investigates the CC-LC circuits in both rodent and human models by using pupil-evoked responses (PERs) as a non-invasive index of LC-NA system engagement. In rodents, intracortical stimulation across eight CC areas revealed that anterior- (ACC) and midcingulate (MCC) subregions evoked rare autonomic effects but robust pupil dilation, with amplitude increasing along the caudorostral and dorsoventral axes. PERs were abolished following DSP-4-mediated depletion of the LC-NA system, confirming the critical role of this system in the PERs. These findings suggest a clear functional parcellation of the rodent CC in its capacity to drive LC activity. To explore the relevance of this organization in humans, we applied single-pulse transcranial magnetic stimulation (TMS) to homologous CC subregions in healthy participants, specifically the pregenual anterior cingulate cortex (pACC) and anterior mid-cingulate cortex (aMCC). TMS evoked intensity-dependent PERs, with aMCC stimulation producing fast, phasic responses and pACC stimulation yielding more sustained effects. These PERs were dissociable from global autonomic effects. Intracortical stimulation in humans (epileptic patients) corroborated these findings, showing significant PERs without general autonomic activation. These results demonstrate that specific subregions of the CC can differentially drive LC-NA activity consistently across species. Furthermore, high-intensity stimulation of the CC improved behavioral performance, consistent with phasic LC-mediated enhancement of cognitive performance. The use of PER as a biomarker thus provides a novel, non-invasive tool to probe the CC–LC circuits and opens new avenues for investigating its role in arousal regulation, motor control, and cognition under normal as well as pathological conditions.
Keywords: Transcranial magnetic stimulation – Pupillometry – Biomarker – Cingulate cortex – Locus coeruleus
Publication
Cingulate cortex Stimulation drives distinct pupillary responses in rat via recruitment of noradrenergic neurons in the locus coeruleus
Vianney Salvi, Gilles Courtand, Philippe de Deurwaerdère, Laura Cardoit, Stéphane Valerio, Sébastien Delcasso, François Georges, Thomas Michelet.
Cerebral Cortex. 2025-05-01. 35(5)
10.1093/cercor/bhaf085
Jury
- Dr. MICHELET Thomas – Maître de conférences – Université de Bordeaux – Directeur de thèse
- Pr. LANDRY Marc – Professeur des universités ; Université de Bordeaux – Président du jury
- Dr. AMIEZ Céline – Directrice de recherche – stem-cell & Brain Research Institute (Bron) – Rapporteure
- Pr. BENOIT-MARAND Marianne – Professeure des universités – Université de Poitiers – Rapporteure
- Pr. DUQUE Julie – Professeure des universités – Institute of Neuroscience Université catholique Louvain (Bruxelle, Belgique) – Examinatrice
- Dr GARCIA-LARREA Luis – Directeur de recherche, Centre de Recherche en Neurosciences de Lyon (Bron) – Examinateur