Neural circuit mechanisms controlling non-homeostatic feeding

强迫进食是美国肥胖症流行的主要原因，超过35%的人 成年人现在被归类为超重或肥胖。行为结果，如强迫 进食源于遗传、先天行为和学习的复杂交互作用 以前的经历。提示-食物协会(例如，广告，在电视前吃饭， 等)在饥饿时期形成的记忆会导致持久的记忆，这种记忆控制着 动态平衡过度消费。然而，神经电路，特别是分子细胞 类型，管理此行为的定义不是很好。使用一种原创的范式，导致 在吃饱了的小鼠中，通过上下文线索，我确立了孤岛的作用 大脑皮层，特别是岛叶皮质内的NOS1神经元，作为学习能力的关键媒介 过度消费。这些神经元本身并不起到平衡摄食的作用，而是 因此假设提供自上而下控制的动态平衡馈电电路来控制 食物摄入量。此外，从岛叶皮质到中央杏仁核的投射是必要的。 以产生这种过度消费反应。在这笔赠款的指导K阶段，我分析了 分子定义的皮质-杏仁核环路在过量消费中的作用 岛叶皮质NOS1神经元的杏仁核靶点。在独立阶段(R00)，我将 通过对脑岛NOS1至中央进行活体钙成像来进一步了解这一点 杏仁核在行为过程中的回路。我还将利用逆行跟踪技术来检查 直接投射到岛叶皮质神经元的细胞类型的区域和分子图谱 控制过度消费，并因果测试他们如何在功能上参与到非 动态平衡进食。这些数据一起，将建立一个细胞类型的特定电路 岛叶皮质，控制对环境刺激的过度消费。此数据将 扩展与摄食行为有关的高级大脑区域的知识，并可能导致 开发新的治疗方法来控制暴饮暴食。

Compulsive eating is a major contributor to the obesity epidemic in the US, as over 35% of adults are now classified as overweight or obese. Behavioral outcomes such as compulsive eating derive from a complex interaction of genetics, innate behaviors and learning about previous experiences. Cue-food associations (e.g. advertising, eating in front of the television, etc.) that are formed during periods of hunger lead to long-lasting memories that control non- homeostatic overconsumption. However, the neural circuitry, and specifically the molecular cell types, governing this behavior are not well defined. Using an original paradigm that induced overconsumption in sated mice with contextual cues, I have established a role of the insular cortex, and specifically Nos1 neurons within the insular cortex, as critical mediators of learned overconsumption. These neurons do not play a role in homeostatic feeding itself and are therefore hypothesized to provide top down control of homeostatic feeding circuitry to control food intake. Moreover, a projection from the insular cortex to the central amygdala is necessary to generate this overconsumption response. In the mentored K-phase of this grant, I analyzed the role of a molecularly defined cortical-amygdalar circuit in overconsumption and determined the amygdala targets of insular cortex Nos1 neurons. In the independent phase (R00), I will further this understanding by employing in vivo calcium imaging to the insula Nos1 to central amygdala circuit during behavior. I will also utilize retrograde tracing techniques to examine the regions and molecularly profile the cell types that directly project to the insular cortex neurons that control overconsumption, and test causally how they are functionally involved in non- homeostatic feeding. Together, these data will establish a cell-type specific circuit through the insular cortex that controls overconsumption in response to environmental stimuli. This data will expand the knowledge of higher-order brain regions involved in feeding behavior and may lead to the development of novel therapeutic avenues to control overeating.