Contributions of activity-defined cortical ensembles to brainwide reward processing

项目总结 这一建议试图确定特定的神经活动模式在前额内侧的贡献。 在寻求奖励的任务中，大脑皮质(MPFC)与全脑的奖励处理有关。众所周知，mPFC是 对于处理环境中的奖励和选择适当的奖励行为非常重要。一个 在我们理解为什么mPFC对这些行为很重要的过程中，缺少的一环是决定 MPFC中的神经元活动驱动整个大脑的神经元影响个人的行为。在这份提案中， 通过利用最新的技术来监控和操纵神经活动，我计划测试 MPFC内特定神经元集合对全脑活动的功能贡献。 我将专门测试巴甫洛夫奖赏寻找任务背后的神经动力学，该任务模拟了 驱动奖励(和毒品)寻求的某些环境线索，这是mpfc与之密切相关的现象 已链接。在目标1中，我将使用双光子钙成像来测量单个mpfc神经元的活动。 而老鼠则在舔蔗糖奖励，以响应奖励预测线索。然后我会用一种光遗传 用图案化激光照射选择性激活特定mPFC神经元的方法，产生靶向 人口活动模式的变化。通过确定哪些活动影响鼠标在 任务，这个目标将解决关于mPFC中种群编码的哪些方面决定其影响的假设 在行为上。在目标2中，我将使用高密度记录设备(神经像素探针)来测量 在处理mPFC细胞亚群的同时，在mPFC的九个主要输出区域中有数千个神经元 寻找奖赏的任务。在这个目标中，我将确定mPFC活动的操纵如何改变与奖励相关的 代表整个大脑，在mPFC形成的神经回路机制上磨练 追求报酬的行为。这些目标将共同确定mPFC中不同的细胞集合 协调全脑神经活动以指导奖赏寻求，以及更广泛地说，如何整合神经元 在分布式电路中用于产生行为的功能。 这一系列研究将与涉及奖赏加工的障碍(如成瘾)特别相关。 神经系统中的系统。MPFC已经成为临床干预的一个有趣的领域，因为它 在复发中的作用。了解mPFC人口活动的哪些特征参与了 寻找奖赏，以及mPFC如何与其他大脑区域互动，将极大地提高对 我们可以针对mPFC进行治疗。

Project summary This proposal seeks to establish the contribution of specific patterns of neural activity in the medial prefrontal cortex (mPFC) to brainwide reward processing during reward-seeking tasks. The mPFC is known to be important for processing rewards in the environment and selecting the appropriate reward-seeking actions. A missing link in our understanding of why mPFC is important for these behaviors is determining how patterns of neuronal activity in mPFC drive neurons across the brain to influence an individual’s behavior. In this proposal, by taking advantage of the most recent technologies to monitor and manipulate neural activity, I plan to test the functional contribution of specific ensembles of neurons in mPFC to the brainwide activity. I will specifically test the neural dynamics underlying a Pavlovian reward-seeking task that models the ability of certain environmental cues to drive reward (and drug) seeking, a phenomenon with which mPFC is closely linked. In aim 1, I will use two-photon calcium imaging to measure the activity of individual mPFC neurons while mice are licking for sucrose reward in response to reward-predicting cues. I will then use an optogenetic approach with patterned laser illumination to selectively activate specific mPFC neurons, producing targeted alteration of population activity patterns. By determining which activity impacts the mouse’s behavior during the task, this aim will address hypotheses about which aspects of population coding in mPFC determine its impact on behavior. In aim 2, I will use high density recording devices (Neuropixels probes) to measure the activity of thousands of neurons in nine major output regions of mPFC while manipulating subsets of mPFC cells during the reward-seeking task. In this aim I will determine how manipulations of mPFC activity change reward-related representations across the brain, honing in on the neural circuit mechanisms by which mPFC shapes reward-seeking behavior. Together these aims will establish how different ensembles of cells in mPFC coordinate brain-wide neural activity to guide reward seeking, and more generally how ensembles of neurons function in distributed circuits to generate behavior. This line of research will have particular relevance to disorders (like addiction) that involve reward-processing systems in the nervous system. The mPFC is already a region of interest for clinical intervention because of its role in relapse. Understanding which features of mPFC population activity participate in which aspects of reward seeking, as well as how mPFC interacts with other brain regions, will greatly improve the precision with which we can target mPFC therapeutically.