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性记忆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缺陷。我们的初步研究表明，成年大鼠在接近预期未来事件时（而不是在其他时间），在正在进行的任务中表现受损，支持了这一假设。工作假设是，随着年龄的增长，前瞻记忆的缺陷将转化为在正在进行的任务中选择性地节省表现。因为对未来事件的预期会对正在进行的活动产生有害的副作用，因此预期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约）。首席研究员将通过实现两个具体目标来验证中心假设：(1)开发与年龄相关的前瞻性记忆衰退的啮齿动物模型。我们将使用横断面和纵向设计来测试前瞻记忆的下降可以通过在我们的前瞻记忆任务中节省正在进行的表现来衡量的工作假设。我们还将在一项纵向研究中检验自愿运动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。我们将测试成年大鼠预测未来特定时间的工作假设，暂时脱离未来计划，并在新环境中部署所学计划。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、失忆症或其他人类记忆病理相关的记忆缺陷的见解，识别控制前瞻性记忆的机制具有巨大的潜力，可以显著造福社会。确定前瞻记忆的基本认知机制将使未来的研究能够确定啮齿动物在正常衰老过程中哪些潜在过程受到保护或受损；这些知识可能最终用于开发自然发生的机制，以防止与年龄相关的认知障碍。理解和利用认知的保护作用可能最终产生新的治疗方法来治疗与年龄相关的认知衰退。如果我们要提高对前瞻记忆的神经基质的理解，并促进人类记忆障碍治疗的发展，就有必要确定控制前瞻记忆的机制。事实上，改善记忆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提供了开发有针对性的药理学和分子疗法的潜力，以治疗困扰正常和无序衰老的认知衰退。

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.