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感至关重要。相反，病理性享乐功能障碍包括丧失积极情绪(快感缺失)和/或过度负面情绪(烦躁不安)，对患有情绪障碍的人会产生毁灭性的后果。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促进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/神经化学享乐生成网络，它放大了愉悦，测量为典型的口面部对甜味的享乐影响的‘喜欢’反应，这与人类和其他哺乳动物共享的大脑机制和进化起源。产生快感的大脑网络包含解剖上分布的立方毫米的热点或亚区，位于伏隔核和腹侧苍白球的前脑深部结构中。这些大脑热点独特地能够对特定的神经化学刺激做出反应，产生自然感觉愉悦的享乐性增强。然而，目前尚不清楚热点内产生享乐性增强的实际神经机制。同样未知的是，享乐主义热点如何在功能上合作，作为一个回路产生愉悦，或者它们如何与更大的大脑调节回路相互作用。这里提出的研究将使用光遗传学技术来识别伏隔核和腹侧苍白球热点内产生享乐性增强影响的神经元机制。这些研究还将确定控制积极情绪产生的电路水平的大脑交互作用，并将调查热点地区的功能障碍如何导致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.