A rodent model of prospective memory

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，并开发用于理解记忆障碍的神经解剖学指导的理论框架。目前探索性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。核心假设是，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表现缺陷。我们的初步研究表明，成年大鼠在预期的未来事件发生时（而不是在其他时间），在正在进行的任务中表现受损，支持这一假设。工作假设是，随着年龄的增长，前瞻性记忆的缺陷将转化为在正在进行的任务中选择性地保留表现。因为预测未来事件会对正在进行的活动产生有害的副作用，所以预期前瞻性记忆的下降会减弱有害的副作用（即，在执行正在进行的任务的能力上产生相对的节省）。主要研究者将通过完成两个具体目标来检验中心假设：（1）建立前瞻性记忆年龄相关性下降的啮齿动物模型。我们将测试的工作假设，前瞻性记忆的下降，可以通过节省正在进行的表现在我们的前瞻性记忆任务使用横截面和纵向设计。我们还将在纵向研究中检验自愿锻炼对前瞻记忆产生保护作用的假设。(2)识别前瞻记忆的基本认知机制。我们将测试的工作假设，成年大鼠预期在未来的特定时间，暂时脱离未来的计划，并部署在一个新的背景下学习的计划。该项目的健康相关性：识别管理前瞻性记忆的机制具有巨大的潜力，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学相关的记忆缺陷的见解，显着造福社会。确定前瞻记忆的基本认知机制将使未来的研究能够确定哪些潜在的过程在啮齿动物的正常衰老过程中受到保护或受损;这些知识最终可能用于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可能最终产生新的治疗方法，以应对与年龄相关的认知下降。如果我们要提高对前瞻记忆潜在神经基质的理解，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，改善记忆力是阿尔茨海默病和与年龄相关的认知衰退的治疗的重要目标。最终，对前瞻性记忆的更好理解提供了开发有针对性的药物和分子治疗方法的潜力，这些药物和分子治疗方法会影响正常和无序的衰老。

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.