NEURAL CIRCUITRY MEDIATING BEHAVIORAL FLEXIBILITY

神经回路调节行为灵活性

• 批准号: 10121211
• 负责人: Elizabeth A West
• 金额: $ 30.94万
• 依托单位: ROWAN UNIVERSITY SCHOOL/OSTEOPATHIC MED
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-01 至 2023-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10121211
• 关键词: Administrative Supplement; Affect; Alzheimer disease screening; Alzheimer' s Disease; Alzheimer' s disease model; Alzheimer' s disease pathology; Alzheimer' s disease patient; Alzheimer' s disease risk; Applications Grants; Award; Behavior; Behavior Control; Behavioral; Brain; Brain region; Cells; Chronic; Cocaine; Cognition; Cognitive; Corpus striatum structure; Cost-Benefit Analysis; Cues; Data; Decision Making; Deformity; Dementia; Disease; Dorsal; Environment; Equilibrium; Exhibits; Face; Future; Goals; Impaired cognition; Impairment; Investigation; Judgment; Lateral; Lead; Learning; Link; Medial; Mediating; Memory Loss; Memory impairment; Modeling; Neurons; Nucleus Accumbens; Outcome; Parents; Pathway interactions; Patients; Pattern; Performance; Pharmaceutical Preparations; Phase; Phenotype; Predisposition; Prefrontal Cortex; Process; Quality of life; Rattus; Recording of previous events; Rewards; Severities; Signal Transduction; Substance abuse problem; Substantia nigra structure; Taxes; Techniques; Transgenic Organisms; Work; behavioral impairment; brain circuitry; caudate nucleus; cocaine exposure; cognitive function; drug of abuse; flexibility; gray matter; improved; loss of function; neural circuit; neural network; neurochemistry; neuropathology; neurophysiology; neurotransmission; optogenetics; parent grant; putamen; reinforcer; relating to nervous system; tau Proteins

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.

项目摘要 平衡习惯和灵活的策略来导航环境是必要的行为 既有认知效率，又能适应变化， 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他们的行为，以应对 改变结果，导致决策失误和认知功能中断。这些 认知功能的缺陷与前额活动的减弱有关。家长奖是 旨在确定可卡因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重要的是，长期吸毒史往往会导致 痴呆症，但对滥用药物和痴呆症之间的联系知之甚少。该电流 行政补充的目的是检查这些电路是如何改变大鼠模型， 阿尔茨海默病（AD，TgF 344-AD）。AD患者的大脑中灰质减少， 相同的大脑区域与SUD中认知灵活性受损有关。我们假设这些 这些变化导致AD患者认知和决策能力的缺陷。例如，早期迹象 包括判断能力的缺陷，这可能反映了大脑回路的变化， 行为灵活性和熟悉任务的困难，这可能反映了大脑回路的变化 习惯性的控制行为。对于这个补充，我们建议描述 转基因AD大鼠（TgF 344-AD）皮质纹状体通路中的神经信号变化 在行为灵活性方面。具体来说，类似于父母补助金，我们将探讨媒体 与腹侧（即，核（nucleus） 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 AD大鼠的神经化学和组织病理学改变。通过此获得的数据 行政补充机制将推动未来的研究和赠款申请， 研究皮质激素回路中神经生理学的改变如何与行为联系起来， 准确预测AD的进展，并与父母奖相结合， 虐待会影响这一进程。