Accumbal Activity Contouring Underlying Cue-Directed Reward Seeking

项目摘要/摘要 滥用药物和生活必需品--食物、社交、生殖--都招募了 在进化上保守的基底节回路，以便整合上下文信息 并促进动作选择。对这一点至关重要的是获得 情境强化预测者和强化者本身。而带刺的投影 腹侧纹状体神经元(SPN)是重要的感觉整合神经。 信息和获得性奖赏显著通过多巴胺输入，它们对获得性线索的编码- 对奖励行为的排序仍不清楚。之前的研究从根本上 关于SPN(多巴胺受体)的两个主要群体的作用不一致 D1和d2表达的SPN)，因为它们与增强有关，可能是因为它们具有 在很大程度上依赖于人口活动的长期系统性破坏，而不是临时定义的 活动轮廓。我的初步结果表明D2-SPN在编码过程中具有选择性作用 强化-预测性语境线索，我假设这些线索会让位于D1-SPN活动 启动马达计划以获得增强剂。我将首先描述一下 线索引导强化行为中D1/D2-SPN活性的亚秒动态 基于钙传感器的荧光技术，并调查人口的预测性 神经活动对行为表现的影响。然后，通过时空受限的调制 对于D2-SPN的光遗传学活性，我将确定线索锁定的D2-的必要分辨率- 线索引导行为的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.