Hedonic hotspot interactions for the generation of 'liking' and 'wanting'

项目摘要：这项建议的主要作用是研究大脑皮质边缘回路 控制对奖励的“喜欢”反应，比如可口的甜味。“喜欢”、“想要”和“学习”是三个词 奖励的不同组成部分，具有可区分的大脑机制，这些机制相互作用，引导动机 1，2大多数关于大脑奖励机制的研究传统上都集中在学习和“想要”上， 因为在以独立的方式衡量“喜欢”以确定其神经机制方面存在挑战。然而， “喜欢”功能障碍是包括抑郁症在内的神经精神障碍的重要组成部分，因此其 了解神经生物学很重要。一种成功测量“喜欢”的方法是情感品味。 反应性测试，它测量不同口味的情感口腔表情，这些表情在不同的地方是相同的 不同种类的动物，并且已经确定了潜在的大脑机制。3-5使用测量的研究 对味道的情感“喜欢”反应表明，“喜欢”是由大脑享乐热点网络控制的。 皮质边缘部位包括伏隔核、腹侧苍白球、眶前皮质和胰岛素。6-12研究 我们的实验室，包括我自己的实验室，已经表明通过光基因激活热点可以放大“喜欢”。 对可口的蔗糖奖励的享乐主义影响的反应。13-16激活享乐热点，放大“喜欢” 也在其他享乐热点招募Fos表达，这表明他们都是同时招募到 行动。然而，尽管这些享乐主义热点被认为是相互招募和相互作用来产生“喜欢”的 增强，连接它们的解剖投影尚未被确定为直接投影 热点之间不存在18，19。目前的提议将调查间接的解剖联系 以及在放大享乐热点电路内的功能招募和相互作用 对令人愉快的奖励的强烈的“喜欢”的表达。第一，解剖的传入和传出投射 将使用顺行和逆行映射来识别NAC、VP、岛和OFC中的享乐热点 识别OFC和NAC热点之间以及NAC之间的潜在汇聚位置的技术 和副总统热点。将使用一种新的高空间分辨率图谱脑图技术来 将连接模式标准化到Swanson大鼠脑图谱。20-22一致的假设 招聘的享乐热点是必要的‘喜欢’增强也将通过激活测试 一个享乐主义热点，同时在品尝“喜欢”的反应中扰乱另一个。来自这些的结果 实验将提供对功能电路的洞察，该功能电路调节可能有助于奖励的“喜欢” 了解各种神经精神障碍。通过拟议的培训，我将学到新的东西 技术，包括神经解剖投影图，脑图谱切片分析，先进 免疫组织化学和复杂的光遗传神经行为分析。NRSA博士前奖学金 将帮助我成为一名成功的、独立的神经科学家。

PROJECT SUMMARY: The primary role of this proposal is to investigate the corticolimbic circuitry that controls `liking' reactions to rewards, such as palatable sweet tastes. `Liking', `wanting', and learning are three distinct components of reward, with distinguishable brain mechanisms, which interact to guide motivated behavior.1,2 Most research on brain reward mechanisms has traditionally focused on learning and `wanting', because of the challenges in measuring `liking' in independent ways to identify its neural mechanisms. Yet, `liking' dysfunction are important components of neuropsychiatric disorders, including depression, and so its neurobiology is important to understand. One method that has successfully measured `liking' is the affective taste reactivity test, which measures affective orofacial expressions to various tastes, which are homologous across various species of animals, and which has identified underlying brain mechanisms.3–5 Studies using measures of affective `liking' reactions to taste have shown `liking' is controlled by a network of brain hedonic hotspots in corticolimbic sites including nucleus accumbens, ventral pallidum, orbitofrontal cortex, and insula.6–12 Research in our lab, including my own, has shown that optogenetically activating the hotspots can amplify `liking' reactions to the hedonic impact of palatable sucrose reward. 13–16 Activating a hedonic hotspot to amplify `liking' also recruits Fos expression in the other hedonic hotspots, suggesting they're all simultaneously recruited into action. 6,17 However, while these hedonic hotspots are thought to mutually recruit and interact to produce `liking' enhancements, the anatomical projections connecting them have not been identified, as direct projections between hotspots do not exist 18,19. The current proposal will investigate the indirect anatomical connections and functional recruitment and interactions within the hedonic hotspot circuitry that amplifies intense `liking' expressions for palatable rewards. First, the anatomical afferent and efferent projections of the hedonic hotspots in NAc, VP, insula, and OFC will be identified, using anterograde and retrograde mapping techniques to identify potential sites of convergence between OFC and NAc hotspots, and between NAc and VP hotspots. A novel high spatial resolution atlas brain mapping technique will be used in order to standardize connectivity patterns onto the Swanson rat brain atlas.20–22 The hypothesis that unanimous recruitment of the hedonic hotspots is necessary for `liking' enhancement will also be tested by activating one hedonic hotspot and simultaneously disrupting another during taste `liking' reactions. Results from these experiments will provide insights into the functional circuitry that mediates reward `liking' that may contribute to understanding various neuropsychiatric disorders. Through the proposed training, I will learn new techniques, including neuroanatomical projection mapping, brain atlas plane of section analysis, advanced immunohistochemistry, and complex optogenetic neurobehavioral analyses. The NRSA predoctoral fellowship will help me transform into a successful, independent neuroscientist.