A rodent model of prospective memory

啮齿类动物的前瞻记忆模型

• 批准号: 8661679
• 负责人: JONATHON D CRYSTAL
• 金额: $ 19.5万
• 依托单位: TRUSTEES OF INDIANA UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-06-01 至 2016-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8661679
• 关键词: Adult; Adverse effects; Age-associated memory impairment; Aging; Alzheimer' s Disease; Amnesia; Animal Model; Animals; Attenuated; Behavior; Biology; Brain Injuries; Clinical; Cognition; Cognitive; Cross-Sectional Studies; Disease; Elements; Episodic memory; Event; Exercise; Failure; Family; Fostering; Future; Goals; HIV Infections; Health; Healthcare; Home environment; Human; Impaired cognition; Impairment; Intention; Knowledge; Learning; Life; Long-Term Care; Longitudinal Studies; Measures; Memory; Memory Disorders; Memory impairment; Methods; Modeling; Molecular; Neurobiology; Outcome; Parkinson Disease; Pathology; Patients; Performance; Pharmaceutical Preparations; Population; Positioning Attribute; Pre-Clinical Model; Principal Investigator; Process; Public Health; Rattus; Relative (related person); Resources; Rodent; Rodent Model; Societies; Specificity; Syndrome; Testing; Time; Translating; Translational Research; Traumatic Brain Injury; United States National Academy of Sciences; Work; age related; animal model development; base; cognitive function; cost; design; effective therapy; flexibility; forgetting; human disease; improved; innovation; insight; longitudinal design; mild cognitive impairment; neuromechanism; normal aging; novel; novel therapeutic intervention; pre-clinical; prospective; prospective memory; protective effect; public health relevance; relating to nervous system; research study; socioeconomics; therapy development

DESCRIPTION (provided by applicant): The long-range goal is to understand how animals process and remember events in time and develop a neuro- anatomically guided theoretical framework for understanding memory disorders. The objective of the present exploratory R21 application is to begin to apply an animal model of prospective memory in rats to aging and identify its basic underlying cognitive mechanisms. The central hypothesis is that activation of prospective memory produces a selective deficit in performance in an ongoing task when anticipation of a future event is greatest. Our preliminary studies, which show an impairment in performance in an ongoing task near the time of an anticipated future event in adult rats (but not at other times), support this hypothesis. The working hypothesis is that deficits in prospective memory with aging will translate into selective sparing of performance in an ongoing task. Because anticipating a future event produces a deleterious side effect on ongoing activity, a decline in prospective memory is expected to attenuate the deleterious side effect (i.e., produce a relative sparing in the ability to carry out ongoing tasks). The Principal Investigator will testthe central hypothesis by accomplishing two specific aims: (1) To develop a rodent model of age-related decline in prospective memory. We will test the working hypothesis that a decline in prospective memory can be measured by sparing of ongoing performance in our prospective-memory task using cross sectional and longitudinal designs. We will also test the hypothesis that voluntary exercise produces protective effects on prospective memory in a longitudinal study. (2) To identify basic cognitive mechanisms in prospective memory. We will test the working hypothesis that adult rats anticipate a specific time in the future, temporarily disengage from a future plan, and deploy a learned plan in a novel context. Health relatedness of the project: Identifying mechanisms that govern prospective memory holds enormous potential to significantly benefit society by providing insights into deficits in memory associated with aging, mild cognitive impairment, Alzheimer's disease, brain injuries, amnesia, or other human memory pathologies. Identifying the basic cognitive mechanisms of prospective memory will enable future research to identify which underlying processes are protected or impaired during normal aging in rodents; this knowledge may ultimately be used to exploit naturally occurring mechanisms that may protect against age-related cognitive impairments. Understanding and exploiting protective effects on cognition may ultimately yield novel therapeutic approaches to age-related declines in cognition. Identifying mechanisms that govern prospective memory is necessary if we are to improve our understanding of the neural substrates underlying prospective memory and foster development of treatments for human memory disorders. Indeed, improving memory is an important objective for therapies of Alzheimer's disease and age-related cognitive decline. Ultimately, a better understanding of prospective memory offers the potential to develop targeted pharmacological and molecular treatments for cognitive decline that afflict normal and disordered aging.

描述(由申请人提供)：长期目标是了解动物如何及时处理和记忆事件，并开发一个神经解剖学指导的理论框架来理解记忆障碍。本探索性R21应用的目的是开始将大鼠前瞻记忆的动物模型应用于衰老，并确定其基本的潜在认知机制。中心假设是，当对未来事件的预期最大时，前瞻记忆的激活会在正在进行的任务中产生选择性的成绩缺陷。我们的初步研究表明，在成年大鼠预期的未来事件发生时(但在其他时间不会)，在正在进行的任务中表现出损害，支持这一假设。工作假说是，随着年龄的增长，前瞻记忆的缺陷将转化为对正在进行的任务中表现的选择性保留。因为对未来事件的预测会对正在进行的活动产生有害的副作用，预期记忆力的下降预计会减弱有害的副作用(即，在执行正在进行的任务的能力方面相对较少)。首席研究员将通过实现两个具体目标来检验中心假设：(1)建立与年龄相关的前瞻记忆衰退的啮齿动物模型。我们将使用横截面和纵向设计来检验这一工作假设，即前瞻记忆的下降可以通过在我们的前瞻记忆任务中保留正在进行的表现来衡量。我们还将在一项纵向研究中测试自愿锻炼对前瞻性记忆产生保护作用的假设。(2)明确前瞻记忆的基本认知机制。我们将测试工作假设，即成年大鼠预测未来的特定时间，暂时脱离未来计划，并在新的背景下部署学习的计划。项目的健康相关性：通过提供与衰老、轻度认知障碍、阿尔茨海默病、脑损伤、健忘症或其他人类记忆病理相关的记忆缺陷的洞察，识别控制前瞻记忆的机制具有显著造福社会的巨大潜力。识别前瞻记忆的基本认知机制将使未来的研究能够确定在啮齿动物的正常衰老过程中，哪些潜在过程受到保护或受损；这些知识最终可能被用来利用自然发生的机制，这些机制可能会防止与年龄相关的认知障碍。理解和利用对认知的保护作用最终可能会产生治疗与年龄相关的认知下降的新方法。如果我们想要更好地理解前瞻记忆背后的神经基础，并促进人类记忆障碍治疗方法的发展，那么识别支配前瞻记忆的机制是必要的。事实上，改善记忆力是治疗阿尔茨海默病和与年龄相关的认知衰退的一个重要目标。最终，对前瞻记忆的更好理解为开发有针对性的药物和分子疗法提供了可能性，以治疗认知衰退，这些认知衰退困扰着正常和紊乱的衰老。