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• W4283788811 abstract "Abstract Disrupted operations of the reward circuit are thought to underlie major emotional disorders including depression and drug abuse 1–3 . These disorders commonly arise following early life stress 4,5 ; however, how stress early in life enduringly impacts reward circuit functions to promote disease remains unclear. Here, we discover and characterize a novel stress-sensitive reward-circuit projection connecting the basolateral amygdala (BLA) and nucleus accumbens (NAc) that co-expresses GABA and the stress-reactive neuropeptide corticotropin-releasing hormone (CRH). We then identify a crucial role for this projection in executing the disrupted reward behaviors provoked by early-life adversity (ELA): Chemogenetic and optogenetic stimulations of the CRH GABA BLA→NAc projection in typically reared mice suppressed several reward seeking behaviors, recapitulating deficits resulting from ELA and demonstrating a key contribution of this pathway in the normal operations of the reward circuit. Next, inhibition of the CRH GABA BLA→NAc projection in adult mice that experienced ELA restored typical reward behaviors in these mice, and, in contrast, had little effect in typically reared mice, indicating a selective ELA-induced maladaptive plasticity of this reward-circuit projection. We discover a novel, stress-sensitive, reward inhibiting projection from the BLA→NAc with unique molecular features, which may provide targets for intervention in disabling mental illnesses." @default.
• W4283788811 created "2022-07-04" @default.
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• W4283788811 date "2022-07-03" @default.
• W4283788811 modified "2023-10-02" @default.
• W4283788811 title "Stress-induced plasticity of a novel CRH^GABA projection disrupts reward behaviors" @default.
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• W4283788811 doi "https://doi.org/10.1101/2022.07.01.498504" @default.
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