Accumbal Activity Contouring Underlying Cue-Directed Reward Seeking

项目摘要/摘要 滥用的毒品和生活必需品-食物、社会交往、生育-都招募了 进化上保守的基底神经节回路，以便整合上下文信息 并且便于动作选择。对此至关重要的是获得之间的关联关系 上下文强化预测器和验证器本身。当多刺的突起 腹侧纹状体的神经元（SPNs）已知是感觉神经元的重要整合者。 信息和通过多巴胺输入的学习奖励显着性，他们对学习线索的编码- 奖励行为序列仍然未知。以前的研究从根本上 不同意关于两个主要群体的SPN（多巴胺受体）的作用， D1和D2表达的SPN），因为它们与强化有关，也许是因为它们具有 在很大程度上依赖于人口活动的长期系统性破坏，而不是时间上的定义 活动轮廓。我的初步结果表明，D2-SPNs在编码中的选择性作用 预测性的上下文线索，我假设然后让位给D1-SPN活动 这是启动运动程序以获得运动细胞的基础。首先，我将描述 线索导向强化行为中D1/D2-SPN活动的亚秒级动力学 钙传感器为基础的荧光技术，并调查人口的预测性 神经活动对行为表现的影响然后，通过时空限制调制 的D2-SPN活动使用光遗传学，我将确定线索锁定的D2-SPN的必要分辨率。 线索导向行为的SPN活动。

Project Abstract/Summary Both drugs of abuse and necessities for life—food, socialization, procreation—recruit the evolutionarily conserved circuitry of the basal ganglia in order to integrate contextual information and facilitate action selection. Critical to this is the acquisition of associative relations between contextual reinforcement predictors and reinforcers themselves. While the spiny projection neurons (SPNs) of the ventral striatum are known to be important integrators of sensory information and learned reward salience through dopamine input, their encoding of learned cue- to-reward behavioral sequencing remains unknown. Previous studies have fundamentally disagreed with respect to the roles of the two primary populations of SPNs (dopamine receptor D1- and D2-expressing SPNs) as they pertain to reinforcement, perhaps because they have largely relied on long-term systemic disruption of population activity rather than temporally defined activity contours. My preliminary results point to a selective role of D2-SPNs in encoding reinforcement-predictive contextual cues, which I hypothesize then give way to D1-SPN activity underlying the initiation of motor programs to acquire reinforcers. I will first characterize the subsecond dynamics of D1/D2-SPN activity during cue-directed reinforcement behavior using calcium-sensor based fluorometric techniques, and investigate the predictivity of population neural activity on behavioral performance. Then, through spatiotemporally-restricted modulation of D2-SPN activity using optogenetics, I will determine the necessary resolution of cue-locked D2- SPN activity for cue-directed behavior.