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Papers of the Week

Papers: 15 Apr 2023 - 21 Apr 2023

Basic Science

Animal Studies, Molecular/Cellular, Neurobiology


2023 Apr 17

Nat Commun




Editor's Pick

The basolateral amygdala-anterior cingulate pathway contributes to depression-like behaviors and comorbidity with chronic pain behaviors in male mice.


Becker LJ, Fillinger C, Waegaert R, Journée SH, Hener P, Ayazgok B, Humo M, Karatas M, Thouaye M, Gaikwad M, Degiorgis L, Santin MDN, Mondino M, Barrot M, Ibrahim EC, Turecki G, Belzeaux R, Veinante P, Harsan LA, Hugel S, Lutz PE, Yalcin I


While depression and chronic pain are frequently comorbid, underlying neuronal circuits and their psychopathological relevance remain poorly defined. Here we show in mice that hyperactivity of the neuronal pathway linking the basolateral amygdala to the anterior cingulate cortex is essential for chronic pain-induced depression. Moreover, activation of this pathway in naive male mice, in the absence of on-going pain, is sufficient to trigger depressive-like behaviors, as well as transcriptomic alterations that recapitulate core molecular features of depression in the human brain. These alterations notably impact gene modules related to myelination and the oligodendrocyte lineage. Among these, we show that Sema4a, which was significantly upregulated in both male mice and humans in the context of altered mood, is necessary for the emergence of emotional dysfunction. Overall, these results place the amygdalo-cingulate pathway at the core of pain and depression comorbidity, and unravel the role of Sema4a and impaired myelination in mood control.