Neural Dynamics Underlying Feeding

 描述（由申请人提供）：更深入地了解肥胖的生物起源将需要映射控制进食的神经网络。控制进食的两个关键神经群是下丘脑中的AgRP和POMC神经元。尽管在过去的20年里对这些细胞进行了广泛的研究，但对它们在体内的自然动力学知之甚少。我们用纤维光度法记录清醒小鼠AgRP和POMC神经元的自然活动。使用这种方法，我们已经发现，AgRP和POMC神经元迅速（秒），并通过与食物相关的感官线索显着调制。这种调节是细胞类型特异性的，对食物的适口性和营养敏感 吃之前，先吃一点东西。这些数据表明存在一个意想不到的神经通路，通过该通路，食物的感官检测产生AgRP和POMC神经元活性的快速预期变化。重要的是，这种快速调节为AgRP和POMC神经元提供了一种机制，将感觉和享乐线索与有关营养状态的稳态信息整合在一起，这表明这些“一阶”神经元的作用比目前所认识的更为复杂。我们建议在这里描绘的神经机制的显着快速调节这些细胞的食物检测。我们建议进一步探索下游的途径，这些感官线索的沟通，以了解他们的角色在一个分布式的喂养网络。

 DESCRIPTION (provided by applicant): A deeper understanding of the biologic origins of obesity will require mapping the neural networks that control feeding. Two key neural populations that control feeding are AgRP and POMC neurons in the hypothalamus. Despite extensive study of these cells over the past 20 years little is known about their natural dynamics in vivo. We have used fiber photometry to record the natural activity of AgRP and POMC neurons in awake behaving mice. Using this approach we have discovered that AgRP and POMC neurons are rapidly (seconds) and dramatically modulated by sensory cues associated with food. This regulation is cell-type-specific, is sensitive to food palatability and nutritional state, and occurs before any food is consumed. These data indicate the existence of an unanticipated neural pathway by which sensory detection of food generates rapid anticipatory changes in the activity of AgRP and POMC neurons. Importantly, this rapid regulation provides a mechanism for AgRP and POMC neurons to integrate sensory and hedonic cues with homeostatic information about nutritional state, suggesting a more complex role for these "first order" neurons than is currently appreciated. We propose here to delineate the neural mechanisms underlying the remarkable rapid regulation of these cells by food detection. We propose further to explore the downstream pathways to which these sensory cues are communicated in order to understand their role within a distributed feeding network.