PDF(Pubmed)
Abstract：
Stress has been shown to promote the development and persistence of binge eating behaviors. However, the neural circuit mechanisms for stress-induced binge-eating behaviors are largely unreported. The endogenous dynorphin (dyn)/kappa opioid receptor (KOR) opioid neuropeptide system has been well established to be a crucial mediator of the anhedonic component of stress. Here, we aimed to dissect the basis of dynorphinergic control of stress-induced binge-like eating behavior. We first established a mouse behavioral model for stress-induced binge-like eating behaviors. We found that mice exposed to stress increased their food intake of familiar palatable food (high fat, high sugar, HPD) compared to non-stressed mice. Following a brain-wide analysis, we isolated robust cFos-positive cells in the Claustrum (CLA), a subcortical structure with highly abundant KOR expression, following stress-induced binge-eating behavior. We report that KOR signaling in CLA is necessary for this elevated stress-induced binge eating behavior using local pharmacology and local deletion of KOR. In vivo calcium recordings using fiber photometry revealed a disinhibition circuit structure in the CLA during the initiation of HPD feeding bouts. We further established the dynamics of endogenous dynorphinergic control of this behavior using a genetically encoded dynorphin biosensor, Klight. Combined with 1-photon single-cell calcium imaging, we report significant heterogeneity with the CLA population during stress-induced binge eating and such behavior attenuates local dynorphin tone. Furthermore, we isolate the anterior Insular cortex (aIC) as the potential source of endogenous dynorphin afferents in the CLA. By characterizing neural circuits and peptidergic mechanisms within the CLA, we uncover a pathway that implicates endogenous opioid regulation stress-induced binge eating.
摘要：
压力已被证明可以促进暴饮暴食行为的发展和持续。然而,应激诱导暴饮暴食行为的神经回路机制在很大程度上没有报道。内源性强啡肽（dyn）/κ阿片样受体（KOR）阿片样神经肽系统已被公认为是压力无张力成分的关键介质。这里,我们旨在剖析应激诱导的暴饮暴食行为的强迫性能控制的基础。我们首先建立了应激诱导的暴饮暴食行为的小鼠行为模型。我们发现，暴露在压力下的小鼠增加了他们熟悉的可口食物的摄取量（高脂肪，高糖,HPD）与非应激小鼠相比。经过全脑分析,我们在Claustrum（CLA）中分离出强大的cfos阳性细胞，具有高度丰富的KOR表达的皮质下结构，跟随压力引起的暴饮暴食行为。我们报告说，使用局部药理学和局部删除KOR，CLA中的KOR信号传导对于这种升高的应激引起的暴饮暴食行为是必需的。使用纤维光度法进行的体内钙记录显示，在HPD进食发作开始时，CLA中存在抑制回路结构。我们使用基因编码的强啡肽生物传感器进一步建立了这种行为的内源性强啡肽能控制的动力学，Klight.结合1光子单细胞钙成像，我们报告了在应激诱导的暴饮暴食过程中与CLA人群的显着异质性，这种行为会减弱局部强啡肽的张力。此外，我们分离出岛前皮层（aIC）作为CLA中内源性强啡肽传入的潜在来源。通过表征CLA内的神经回路和肽能机制，我们发现了一条涉及内源性阿片类药物调节应激诱导暴饮暴食的途径。
