Neural circuit mechanisms controlling non-homeostatic feeding

控制非稳态进食的神经回路机制

• 批准号: 10429408
• 负责人: Sarah Stern
• 金额: $ 5.06万
• 依托单位: MAX PLANCK FLORIDA CORPORATION
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-03-01 至 2023-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10429408
• 关键词: Adult; Advertising; Amygdaloid structure; Behavior; Behavioral; Binge Eating; Brain; Brain region; Complex; Cues; Data; Development; Eating; Feeding behaviors; Food; Genetic; Grant; Hunger; Hyperphagia; Instinct; Insula of Reil; Knowledge; Lead; Learning; Mediator of activation protein; Memory; Mentors; Modeling; Molecular; Molecular Profiling; Mus; Neurons; Obesity; Obesity Epidemic; Overweight; Phase; Research; Role; Stimulus; Techniques; Television; Testing; Weight Gain; behavioral outcome; cell type; experience; feeding; in vivo calcium imaging; neural circuit; novel therapeutics; obesity treatment; response; therapy development

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.

强迫性进食是美国肥胖症流行的主要原因， 成年人现在被归类为超重或肥胖。行为结果，如强迫性 饮食来源于遗传、先天行为和学习的复杂相互作用， 以前的经历。暗示食物协会（例如广告，在电视机前吃饭， 等等）。在饥饿期间形成的记忆会导致长期记忆， 自我平衡过度消费然而，神经回路，特别是分子细胞 类型，控制这种行为没有很好地定义。使用一个原始的范例， 在满足的小鼠过度消费与上下文线索，我已经建立了一个作用的岛屿 皮质，特别是岛叶皮质内的Nos 1神经元，作为学习的关键介质， 过度消费这些神经元在稳态进食本身中不起作用， 因此假设提供自上而下的自我平衡进食回路控制 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 产生这种过度消费的反应。在这一资助的指导K阶段，我分析了 分子定义的皮质-杏仁核回路在过度消费中的作用， 岛叶皮层Nos 1神经元的杏仁核靶点。在独立阶段（R 00），我将 通过采用体内钙成像技术， 杏仁核回路我还将利用逆行追踪技术来检查 直接投射到岛叶皮层神经元的细胞类型 控制过度消费，并测试因果关系，他们是如何在功能上参与非- 自我平衡进食总之，这些数据将建立一个细胞类型的特定电路，通过 控制对环境刺激的过度消费的岛叶皮层。这些数据将 扩大了涉及进食行为的高级大脑区域的知识， 发展新的治疗方法来控制暴饮暴食。