Affective neuroscience of taste reactivity

描述（由申请人提供）：对愉快生活事件的积极情感反应对健康的生活功能和幸福至关重要。相反，病理性享乐功能障碍包括积极影响的丧失（享乐缺乏）和/或过度的消极影响（烦躁不安），对情绪障碍患者具有毁灭性的后果。因此，了解大脑情感机制如何产生正常的积极影响，特别是大脑机制如何提高享乐影响的积极强度是至关重要的。我们之前的研究发现了一个特定的神经解剖学/神经化学快感产生网络，可以放大愉悦感，通过对甜味快感影响的原型口面部“喜欢”反应来测量，这与人类和其他哺乳动物的大脑机制和进化起源相同。产生快乐的大脑网络包含解剖学上分布的立方毫米热点或亚区，位于伏隔核和腹侧白球的前脑深部结构中。这些大脑热点是独特的，能够产生自然感官愉悦的快感增强，以响应特定的神经化学刺激。然而，在热点区域产生快感增强的实际神经元机制仍然未知。同样未知的是，快乐热点是如何作为一个回路一起合作产生快乐的，或者它们是如何与更大的调节脑回路相互作用的。本文提出的研究将利用光遗传学技术来确定伏隔核和腹侧苍白球热点内产生享乐增强影响的神经元机制。这些研究还将确定控制积极影响产生的回路水平的大脑相互作用，并将研究热点的功能障碍如何产生病理性快感缺乏和烦躁不安。

DESCRIPTION (provided by applicant): Positive affective reactions to pleasant life events are crucial to healthy life function and well- being. Conversely, pathological hedonic dysfunction involving loss of positive affect (anhedonia) and/or excessive negative affect (dysphoria) has devastating consequences for individuals with mood disorders. Therefore it is crucial to understand how brain affective mechanisms generate normal positive affect, and especially how brain mechanisms boost the positive intensity of hedonic impact. Our previous studies identified a specific neuroanatomical/neurochemical hedonic generating network that amplifies pleasure, measured as prototypical orofacial 'liking' reactions to the hedonic impact of sweetness, which have brain mechanisms and evolutionary origins shared by humans with other mammals. The pleasure-generating brain network contains anatomically distributed cubic-millimeter hotspots or subregions, within deep forebrain structures of nucleus accumbens and ventral pallidum. Those brain hotspots are uniquely able to generate hedonic enhancements of natural sensory pleasure, in response to specific neurochemical stimulation. Yet still unknown are the actual neuronal mechanisms within hotspots that generate hedonic enhancement. Also unknown are how the hedonic hotspots functionally cooperate together to generate pleasure as a circuit, or how they interact with larger regulatory brain circuits. The studies proposed here will use optogenetic techniques to identify the neuronal mechanisms inside hotspots of nucleus accumbens and ventral pallidum that generate hedonic enhancements impact. The studies will also identify circuit-level brain interactions that control the generation of positive affect, and ill investigate how dysfunction in hotspots produces pathological anhedonia and dysphoria.