Cortical interactions underlying memory and decision making in rodent models

啮齿动物模型中记忆和决策的皮质相互作用

• 批准号: RGPIN-2020-06638
• 负责人: Howland, John
• 金额: $ 3.42万
• 依托单位: University of Saskatchewan
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2022
• 资助国家: 加拿大
• 起止时间: 2022-01-01 至 2023-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=743479
• 关键词: Cortical; interactions; underlying; memory; decision

The neurobiological mechanisms supporting cognition remain poorly characterized. Converging lines of evidence suggest that cognitive processes including learning, memory, and decision making rely on activity in cortical regions and other interconnected areas of the distributed meso-cortico-striatal-limbic circuitry. Recent research in my laboratory involving a combination of behavioural testing, pharmacology, and in vivo extracellular recordings has been conducted in rat models in an effort to understand these interactions. The present Discovery Grant Application will focus on advancing our understanding of cortical processing in the behavioural paradigms to assess working memory optimized in my laboratory. The results of these experiments are expected to significantly increase the understanding of advanced cognitive functions such as learning and memory from an integrated behavioural and physiological perspective. HQP under my supervision at the undergraduate, graduate, and postdoctoral levels will continue experiments designed to understand the patterns of activity in medial prefrontal cortex (mPFC) and striatum for working memory capacity as measured in the odour span task. In recent work using in vivo extracellular recordings in rats, we have shown that activity of mPFC neurons during the delay period of the odour span task predicts subsequent performance on the task. Thus, I plan to conduct additional recordings in combination with dopamine receptor pharmacology, optogenetics, and acute stress to examine patterns of frontal-striatal activity that govern span performance. I believe that the findings from these experiments will be useful in refining theories regarding cortical-striatal interactions during cognition. We will also characterize the role(s) of mPFC, posterior parietal cortex (PPC), and their interactions with dorsal striatum in a visuospatial working memory task, the trial-unique-nonmatching-to-location (TUNL) task performed in touchscreen-equipped operant conditioning chambers. The proposed experiments will characterize: 1) the patterns of neural activity in each cortical area during TUNL; 2) involvement of the cortical areas in the sample, delay, and test phases of the task; 3) whether inhibiting task-specific activity patterns with optogenetics impairs performance of TUNL. As few working memory paradigms used in rodents show PPC involvement, these results will increase our understanding of the function of this understudied area of rodent cortex in cognition. Finally, we will assess the roles of orbitofrontal cortex interactions with the PPC in an array of object oddity tests we have recently optimized to allow us to control the modality of the available stimuli. It is expected that the proposed program of research will fundamentally contribute to understanding the detailed mechanisms through which cortical-striatal neural activity enables learning, memory, and decision making.

支持认知的神经生物学机制仍然缺乏特征。越来越多的证据表明，包括学习、记忆和决策在内的认知过程依赖于皮层区域和分布的中皮层-纹状体-边缘系统回路的其他相互连接区域的活动。最近在我的实验室进行的研究，包括行为测试，药理学和体内细胞外记录的组合，已在大鼠模型中进行，以了解这些相互作用。目前的发现资助申请将侧重于推进我们对行为范式中皮层处理的理解，以评估在我的实验室中优化的工作记忆。这些实验的结果有望从综合的行为和生理角度显著增加对高级认知功能（如学习和记忆）的理解。HQP在我的监督下，在本科生，研究生和博士后水平将继续实验，旨在了解内侧前额叶皮层（mPFC）和纹状体的活动模式的工作记忆容量测量的气味跨度任务。在最近的工作中，在大鼠体内细胞外记录，我们已经表明，在延迟期的气味跨度任务的mPFC神经元的活动预测随后的性能上的任务。因此，我计划结合多巴胺受体药理学、光遗传学和急性应激进行额外的记录，以检查控制跨度表现的额纹体活动模式。我相信这些实验的发现将有助于完善认知过程中皮质-纹状体相互作用的理论。我们还将描述mPFC，后顶叶皮层（PPC）的作用，以及它们与背侧纹状体在视觉空间工作记忆任务中的相互作用，在配备触摸屏的操作性条件反射室中执行的试验独特非匹配位置（TUNL）任务。所提出的实验将表征：1）在TUNL期间每个皮层区域中的神经活动模式; 2）皮层区域在任务的样本、延迟和测试阶段中的参与; 3）利用光遗传学抑制任务特异性活动模式是否损害TUNL的性能。由于啮齿类动物中很少有工作记忆范式显示PPC参与，这些结果将增加我们对啮齿类动物皮层这一未充分研究区域在认知中的功能的理解。最后，我们将评估眶额皮质与PPC的相互作用的作用，在一系列的对象古怪的测试，我们最近优化，使我们能够控制可用的刺激的方式。预计拟议的研究计划将从根本上有助于理解皮质-纹状体神经活动使学习，记忆和决策的详细机制。