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中文摘要
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描述(由申请人提供):对愉快的生活事件的积极情感反应对健康的生活功能和福祉至关重要。相反,病理性享乐功能障碍涉及积极情感的丧失(快感缺失)和/或过度的消极情感(烦躁不安),对情绪障碍的个体具有毁灭性的后果。因此,了解大脑情感机制如何产生正常的积极情感,特别是大脑机制如何提高享乐影响的积极强度至关重要。我们以前的研究确定了一个特定的神经解剖学/神经化学享乐生成网络,放大快乐,测量为原型orofacial“喜欢”的反应,甜味的享乐影响,其中有大脑机制和进化的起源共享人类与其他哺乳动物。产生快乐的大脑网络包含解剖学上分布的3毫米热点或子区域,位于前脑深部的丘脑核和腹侧苍白球结构内。这些大脑热点是独特的,能够产生自然感官愉悦的享乐增强,以响应特定的神经化学刺激。然而,仍然未知的是热点内产生享乐增强的实际神经元机制。同样未知的是,享乐热点如何在功能上共同合作,以产生快乐作为一个回路,或者它们如何与更大的调节性大脑回路相互作用。本研究将利用光遗传学技术来确定产生享乐增强效应的丘脑核和腹侧苍白球热点内的神经机制。这些研究还将确定控制积极情绪产生的回路水平的大脑相互作用,并调查热点功能障碍如何产生病理性快感缺乏和焦虑。
英文摘要
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.
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Project II: Circuit Mechanisms of Attentional-Motor Interface Dysfunction in PD Falls
Cue-triggered reward seeking
Cue-triggered reward seeking
Cue-triggered reward seeking
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