Fiche publication
Date publication
janvier 2026
Journal
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
Auteurs
Membres identifiés du Cancéropôle Est :
Dr LUTZ Pierre-Eric
,
Dr YALCIN CHRISTMANN Ipek
,
Dr BARROT Michel
Tous les auteurs :
Journée SH, Mathis VP, Waegaert R, Ozkan S, Langlois E, Ortiz-Teba P, Ayazgok B, Becker LJ, Gaikwad M, Barrot M, Hugel S, Harsan L, Lutz PE, Yalcin I
Lien Pubmed
Résumé
Chronic pain induces long-lasting changes in the anterior cingulate cortex (ACC) activity that contribute to the development of comorbid mood disorders. However, how such alterations propagate throughout the ACC connectome remains to be elucidated. Here, we aimed to study the role of the ACC neurons projecting to the lateral habenula (LHb) (ACC) in chronic pain-induced depression (CPID). CPID was induced using sciatic nerve cuffing in male C57BL/6J mice, and anxiodepressive-like behaviors were evaluated using a battery of behavioral tests. Fiber photometry was used to study the Ca dynamics in the ACC, LHb, and ACC neurons We combined viral Translating Ribosome Affinity Purification (vTRAP) and RNA sequencing to study the molecular alterations in the ACC neurons. Finally, we used an optogenetic approach to study the functional role of this pathway in CPID. Our results confirmed a functional connectivity between the ACC and LHb and demonstrated that this connection plays a critical role in emotional processing. Activation of ACC neurons elicited Ca responses in the LHb and induced anxiodepressive-like behaviors in naive mice. Cell-type specific transcriptomic analysis revealed that CPID altered the expression of genes involved in neuronal excitability, such as genes related to sphingolipid metabolism, glycophospholipid,s and Ca channels in ACC neurons. Interestingly, inhibition of this hyperactivity alleviated chronic pain- but not stress-induced anxiodepressive-like behaviors, demonstrating that the ACC pathway selectively contributed to nerve-injury induced emotional dysregulation. These results reveal that hyperactivity of the neuronal pathway linking the ACC to the LHb is essential for CPID in male mice.
Référence
Neuropsychopharmacology. 2026 01 21;:
