ArticleScience advances2025
A striosomal accumbens pathway drives stereotyped behavior through an aversive Esr1+ hypothalamic-habenula circuit.
Article in Science advances, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
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Who cites it
2 citing papers in PubMed.
- Hippocampal Projections to the Striatal Compartments, Striosome and Matrix, are Spatially Segregated in CA1.bioRxiv : the preprint server for biology · 2026Article
- Sex-associated circadian signaling signatures in the lateral hypothalamus.Frontiers in sleep · 2026Article
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Authors and funding
17 authors.
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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.
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