2025-11-22 カロリンスカ研究所(KI)
<関連情報>
- https://news.ki.se/brain-circuit-controlling-compulsive-behaviour-mapped
- https://www.science.org/doi/10.1126/sciadv.adx9450
ストリオソーム側坐核経路は、嫌悪性のEsr1+視床下部-手根核回路を介して定型行動を駆動する A striosomal accumbens pathway drives stereotyped behavior through an aversive Esr1+ hypothalamic-habenula circuit
Thomas Contesse, Buse Yel Bektash, Marta Graziano, Chiara Forastieri, […] , and Konstantinos Meletis
Science Advances Published:21 Nov 2025
DOI:https://doi.org/10.1126/sciadv.adx9450
Abstract
The lateral hypothalamic area (LHA) integrates external stimuli with internal states to drive the choice between competing innate or value-driven motivated behaviors. Here, we define a striosomal Tac1+/Tshz1+/Oprm1+ neuron subtype in the nucleus accumbens (ACB) that targets Esr1+ LHA neurons that project to the lateral habenula (LHb). Intersectional cell type–specific and input-output defined optogenetic activation of this ACB-LHA-LHb pathway can progressively induce a negative behavioral state that depends on Esr1+ LHA-LHb neural activity. We found that either activation of the D1+ ACB-LHA projection or inhibition of LHA-LHb neurons defined by ACB inputs can drive reward-independent compulsive-like behaviors that generalize across contexts. We found that these complex yet stereotyped behaviors compete with highly motivated states and can override the drive for natural rewards or social interactions. Our findings reveal a discrete Tac1+ striosomal ACB projection targeting the aversive Esr1+ LHA-LHb pathway as a key circuit that promotes stereotyped and compulsive-like behaviors over goal-directed actions.
