NEURAL CIRCUITRY MEDIATING BEHAVIORAL FLEXIBILITY

项目摘要 平衡习惯和灵活的环境导航策略对于行为是必要的 这既是认知上有效的，也是适应变化的，也是破坏这种平衡的扰动 会导致严重的认知障碍。重要的工作集中在患者如何与 物质滥用障碍(SUD)通常表现出难以改变其行为以应对 改变结果，导致糟糕的决策和认知功能中断。这些 认知功能缺陷与前额叶活动减弱有关。家长奖是 旨在确定可卡因的历史如何改变皮质纹状体神经网络信号 导致认知灵活性受损。关键是，慢性吸毒史往往会导致各种形式的 痴呆症，但对滥用药物和痴呆症是如何联系的知之甚少。这股海流 行政补充旨在研究这些回路是如何在大鼠模型中改变的。 阿尔茨海默病(AD，TgF344-AD)。阿尔茨海默病患者大脑皮质灰质减少 与肥胖症认知灵活性受损有关的大脑区域相同。我们假设这些 变化导致阿尔茨海默病患者认知和决策的缺陷。例如，早期迹象 阿尔茨海默病包括两种判断缺陷，这可能反映了大脑电路的变化 熟悉任务中的行为灵活性和困难，这可能反映了大脑回路的变化 习惯性地控制行为所必需的。在本附录中，我们建议将 转基因AD大鼠(TgF344-AD)皮质纹状体通路中神经信号的变化 在行为灵活性方面。具体地说，类似于家长拨款，我们将探索医疗 与腹侧(即伏隔核)相连的前额叶皮质亚区(前额叶和下缘) 和背侧纹状体亚区。我们还将把神经生理学和行为学的改变联系起来 对阿尔茨海默病大鼠神经化学和组织病理学改变的影响。通过此方法获得的数据 行政补充机制将推动未来的研究并批准将 研究大脑皮质环路中神经生理学的改变如何与行为联系在一起 准确预测AD的进展，并结合家长奖，如何用药 虐待会影响这一进程。

Project Summary Balancing habitual and flexible strategies for navigating the environment is necessary for behavior that is both cognitively efficient yet adaptive to change, and perturbations that disrupt this balance can result in significant cognitive impairments. Significant work has focused on how patients with substance abuse disorders (SUD) often shown difficulty altering their behavior to respond to changing outcomes, leading to poor decision-making and disrupted cognitive function. These deficits in cognitive function are linked to dampened prefrontal activity. The parent award is aimed to determine how a history of cocaine alters the corticostriatal neural network signaling that drives impaired cognitive flexibility. Critically, chronic history with drugs often leads to forms of dementia, but little is known about how drugs of abuse and dementia are linked. This current administrative supplement is aimed at examining how these circuits are altered in rat model of Alzheimer’s disease (AD, TgF344-AD). Patients with AD show decreased grey matter in the same brain regions linked to impaired cognitive flexibility in SUDs. We hypothesize that these changes contribute to deficits in cognition and decision-making in AD. For example, early signs of AD include both deficits in judgment, which may reflect changes to brain circuitry necessary for behavioral flexibility and difficulties in familiar tasks, which may reflect changes in brain circuitry necessary for habitual control of behavior. For this supplement, we propose to characterize the neural signaling changes in the Transgenic AD rat (TgF344-AD) in the corticostriatal pathways during behavioral flexibility. Specifically, similar to the parent grant we will explore the medial prefrontal cortex subregions (prelimbic and infralimbic) linked to ventral (i.e., nucleus accumbens) and dorsal striatum subregions. We will also link alterations in neurophysiology and behavioral to neurochemical and histopathological changes in AD rats. Data obtained through this administrative supplemental mechanism will drive future studies and grant applications that will examine how alterations in neurophysiology in corticostrial circuits link to behavior to more accurately predict the progression of AD, and in combination with the parent award, how drugs of abuse affect this progression.