Selective Cortical Networks in Cocaine Seeking

复发是可卡因成瘾的一个长期问题，也是大脑机制的许多重要方面 涉案人员仍不得而知。在大鼠模型中，可卡因复发的一个关键区域是内侧前额叶皮质 (MPFC)；特别是mPFC与伏核(NA)和腹侧被盖区的相互作用 (VTA)是恢复绝迹的可卡因寻觅的关键。该中心的项目1和2的重点是 分子和细胞机制参与mPFC-to-NA途径的消亡和 复职。对mPFC中投射到NA或接收神经元的活动知之甚少。 在这些可卡因行为中，来自VTA的多巴胺(DA)。在这里，我们将使用Fos标记和单元记录 在消退和恢复期间测量mPFC神经元的脉冲活动被识别为投射到 核或壳。我们还将利用TH：：CRE大鼠和最近在 本实验室研究内源性DA释放对大脑皮层前叶神经元冲动活动的影响 在灭绝和恢复期间向NA核投射。总而言之，这些研究将提供一个总体 在可卡因行为中激活的NA投射mPFC神经元的MAP，并测量它们的 关于特定任务刺激的冲动活动和在灭绝或恢复期间的行为 寻找可卡因。这些发现将提供对这些行为相关活动的详细电路分析 关键的mPFC神经元将是推广分子和细胞水平研究结果的重要信息 在这个中心的其他项目中。

Relapse is a persistent problem in cocaine addiction, and many important aspects ofthe brain mechanisms involved remain unknown. One key area for cocaine relapse in the rat model is the medial prefrontal cortex (mPFC); in particular, mPFC interactions with the nucleus accumbens (NA) and ventral tegmental area (VTA) are critical for reinstatement of extinguished cocaine seeking. Projects 1 and 2 in this center focus on molecular and cellular mechanisms involved in the mPFC-to-NA pathway during extinction and reinstatement. Little is known about the activities of neurons in mPFC that project to NA, or that receive dopamine (DA) from VTA, during these cocaine behaviors. Here, we will use Fos labeling and unit recording during extinction and reinstatement to measure impulse activity of mPFC neurons identified as projecting to NA core or shell. We also will capitalize on TH::Cre rats and optogenetics methods recently implemented in our lab to determine the influence of endogenous DA release on impulse activity of prelimbic cortex neurons that project to NA core during extinction and reinstatement. Together, these studies will provide an overall map of NA-projecting mPFC neurons that are activated during cocaine behaviors, and also measure their impulse activities with respect to specific task stimuli and behaviors during exinction or reinstatement of cocaine seeking. These findings will provide a detailed circuit analysis of behavior-related activities in these key mPFC neurons that will be important information to extend results of molecular- and cellular-level studies in other projects of this center.