Contributions of activity-defined cortical ensembles to brainwide reward processing

活动定义的皮质群对全脑奖励处理的贡献

• 批准号: 10229290
• 负责人: David Joshua Ottenheimer
• 金额: $ 6.87万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-05-16 至 2024-05-15
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10229290
• 关键词: Address; Amygdaloid structure; Animals; Area; Automobile Driving; Behavior; Brain; Brain region; Calcium; Cells; Clinical; Code; Cognitive; Communities; Consumption; Cues; Data; Data Set; Decision Making; Devices; Disease; Dorsal; Eating; Electrophysiology (science); Environment; Health; Heterogeneity; Image; Individual; Intervention; Investigation; Knowledge; Lasers; Light; Lighting; Link; Measures; Medial; Mediating; Modeling; Monitor; Motor; Mus; Nervous System Physiology; Nervous system structure; Neurons; Neurosciences; Obesity; Opsin; Output; Pattern; Pharmaceutical Preparations; Population; Prefrontal Cortex; Process; Property; Relapse; Research; Rewards; Role; Sensory; Shapes; Stimulus; Sucrose; System; Technology; Testing; Therapeutic; Time; Ventral Striatum; Ventral Tegmental Area; Viral; Work; addiction; cell cortex; density; improved; interest; neural circuit; neural patterning; neuromechanism; neuronal patterning; novel; optogenetics; relating to nervous system; response; reward processing; sensor; tool; two photon microscopy; two-photon

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.

项目摘要 这项建议旨在建立在内侧前额叶的神经活动的具体模式的贡献 大脑皮层（mPFC）在奖励寻求任务中对全脑奖励处理的影响。已知mPFC是 这对于处理环境中的奖励和选择适当的奖励寻求动作很重要。一 在我们理解为什么mPFC对这些行为很重要的过程中，缺少一个环节，那就是确定 mPFC中的神经元活动驱动整个大脑的神经元来影响个体的行为。在这项提案中， 通过利用最新的技术来监测和操纵神经活动，我计划测试 mPFC中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励寻求任务背后的神经动力学，该任务模拟了 某些环境线索驱动奖励（和药物）寻求，这种现象与mPFC密切相关。 有联系在目标1中，我将使用双光子钙成像来测量单个mPFC神经元的活性 而老鼠则是为了得到蔗糖奖励而舔，以回应奖励预测线索。我会用光遗传学 用图案化激光照射的方法选择性地激活特定的mPFC神经元，产生靶向的 改变人口活动模式。通过确定哪种活动影响小鼠的行为， 任务，这一目标将解决关于mPFC中人口编码的哪些方面决定其影响的假设 关于行为。在目标2中，我将使用高密度记录设备（Neuropixels探针）来测量 在mPFC的九个主要输出区域中的数千个神经元，同时操纵mPFC细胞的子集， 寻求奖励的任务。在这个目标中，我将确定如何操纵mPFC活动改变奖励相关的 大脑中的代表，磨练在神经回路机制，其中mPFC的形状 寻求奖励的行为。这些目标将共同确定mPFC中不同的细胞群 协调全脑神经活动以指导奖励寻求，更一般地说， 在分布式电路中的功能，以产生行为。 这一系列的研究将与涉及奖励加工的疾病（如成瘾）特别相关 神经系统中的系统。mPFC已经是临床干预的感兴趣区域，因为其 在复发中的作用了解中等职业妇女群体活动的哪些特征参与了 奖励寻求，以及mPFC如何与其他大脑区域相互作用，将大大提高精度， 我们可以针对前额叶皮层进行治疗