Dissecting the role of neural inputs in the regulation of AgRP neurons

项目摘要： 适当地调节食物摄入量对于生存是至关重要的，以防止过度喂养或喂养不足。感官信号 通过检测和消费产生的食物可以调节食物的摄入量。外部感官提示，如 食物的视觉和气味以及食物暗示可以加强进食，而来自 胃肠道中的营养物质和膨胀会抑制进食。然而大脑是如何将这两者结合在一起的 调节觅食行为的信息流尚不清楚。下丘脑室旁核内的AgRP神经元 下丘脑弓状核(ARC)是这个问题的一个有用的切入点。ArCAgRP神经元是 都是进食行为的必要条件和充分条件，而且它们已经被证明整合了这两种类型的 跨越两个不同时间尺度的感觉信号：对食物的视觉和气味做出反应的快速抑制，以及 在胃内输送食物的过程中抑制较慢。然而，这些调制信号的来源 对于ARCAgRP对感觉信息的反应，人们知之甚少。我建议在这里解决这个问题 通过系统测试ARCAgRP神经元的两个已知神经输入提出的问题：1.垂体腺苷环化酶 下丘脑室旁核活化肽表达神经元(PVHPACAP)； 瘦素受体在下丘脑背内侧的表达神经元。我会检查一下确切的类型 这些输入中的每一个代表的信息，以及在调制中这些输入中的两个的必要性 AgRP神经元对感觉信息的反应。此外，我将通过以下方式调查一种潜在的机制 哪种营养状态会改变DMHLepR神经元对食物呈现的反应。将这些结果放在一起 将揭示一个关键的神经馈送中心是如何被调节的，并阐明了潜在的机制 在肥胖等不适应的进食行为中，这种感觉信号整合可能会被扰乱。

Project Abstract: Proper regulation of food intake is essential for survival to prevent over- or under-feeding. Sensory signals generated by the detection and consumption of food can modulate food intake. External sensory cues such as the sight and smell of food and food cues can potentiate feeding, while internal sensory information from nutrients and distension in the gastrointestinal tract can inhibit feeding. Yet how the brain integrates these two streams of information to modulate feeding behavior is unclear. Agouti-related peptide (AgRP) neurons in the arcuate nucleus of the hypothalamus (ARC) are a useful entry point into this question. ARCAgRP neurons are both necessary and sufficient for feeding behavior, and they have been shown to integrate these two types of sensory signals across two different time scales: rapid inhibition in response to the sight and smell of food, and slower inhibition during intragastric delivery of food. However, the sources of these signals that modulate ARCAgRP activity in response to sensory information are poorly understood. I propose here to address this question by systematically testing two known neural inputs to ARCAgRP neurons: 1. Pituitary adenylate-cyclase activating peptide expressing neurons in the paraventricular nucleus of the hypothalamus (PVHPACAP), and 2. Leptin receptor expressing neurons in the dorsomedial hypothalamus (DMHLepR). I will examine the exact types of information each of these inputs represents, as well as the necessity of two of these inputs in modulating AgRP neurons in response to sensory information. Additionally, I will investigate a potential mechanism by which nutritional state alters the response of DMHLepR neurons to food presentation. Together these results would reveal how a critical neural feeding center is regulated, as well as illuminate potential mechanisms by which sensory signal integration could become disrupted in maladaptive feeding behaviors such as obesity.