Information theoretic assays of exploration in aged mice

老年小鼠探索的信息论分析

• 批准号: 7048089
• 负责人: STEPHEN J BONASERA
• 金额: $ 18.04万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-06-15 至 2008-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7048089
• 关键词: age difference; aging; animal old age; behavior prediction; behavior test; behavioral /social science research tag; body movement; cognition; dementia; ethology; exploratory behavior; laboratory mouse; learning; memory; model design /development; neural information processing; olfactory stimulus; perception; psychological models; thermodynamics; video recording system; visual perception

DESCRIPTION (provided by applicant): Normal aging is accompanied by alterations in both cognitive and emotional function. While these changes are of modest significance in otherwise healthy elders, they can have devastating impacts in persons with dementia or cognitive impairment. Unfortunately, current knowledge of the basic neuroscience underlying behavioral disturbances in the elderly remains very poorly understood. Aged mice are appropriate models to address this significant deficit. Neurophysiology of the aging mouse brain resembles that seen in man, and many behaviors observable in mice have close human parallels. For example, in both mouse and man there is an age-related decline in gross exploration of a new environment. Exploratory behavior is modulated in a specific manner by different neurotransmitter systems; thus, sophisticated analyses of exploratory behavior can provide important insights into age-related changes in CNS function. Currently, powerful tools to study exploratory behavior are lacking; we propose to develop these tools. We will develop a multiple behavioral state (MBS) representation of arena influences on mouse location, mouse locomotor activity (stop/pausing, turning, and progression), and other mouse ethological parameters (rearing, stretching, grooming, etc.). We will then extend this approach to study how acquisition of place memories alters variables within the MBS model. The entropy rate and predictive information will be calculated for these data and used to quantify the amount of randomness and complexity of the responses. Validation data will be collected in young (6 wk), mid-life (12 month) and aged (>24 month) C57BI6 mouse cohorts. Our preliminary results show that aged mice have less complex novel environment exploratory patterns compared to a younger cohort. The analytic tools developed in this study will be invaluable when evaluating the efficacy of future pharmacological or genetic-based therapies to enhance cognitive and emotional function in patients with dementia.

描述（由申请人提供）：正常衰老伴随着认知和情感功能的改变。尽管这些变化在其他健康的长者中具有适度的意义，但它们可能对痴呆症或认知障碍的人产生毁灭性的影响。不幸的是，当前对老年人中基本神经科学基本行为障碍的知识仍然非常了解。老年小鼠是解决这一重大赤字的合适模型。衰老小鼠脑的神经生理学类似于人类中看到的，并且在小鼠中可观察到的许多行为具有紧密的人类相似之处。例如，在老鼠和人类中，对新环境的总探索的年龄相关。探索行为是通过不同神经递质系统以特定方式调节的。因此，对探索行为的复杂分析可以为与年龄相关的中枢神经系统功能变化提供重要的见解。当前，缺乏研究探索行为的强大工具；我们建议开发这些工具。我们将开发出对小鼠位置，小鼠运动活性（停止/暂停，转弯和进展）以及其他小鼠伦理学参数（饲养，拉伸，修饰等）的多重行为状态（MB）表示。然后，我们将扩展这种方法，以研究获取位置记忆如何改变MBS模型中的变量。熵率和预测信息将针对这些数据计算，并用于量化响应的随机性和复杂性。验证数据将在年轻（6周），中年（12个月）和老年（> 24个月）C57BI6鼠标同类中收集。我们的初步结果表明，与年轻的队列相比，老年小鼠的新型环境探索模式不那么复杂。在评估未来药理学或基于基因的疗法以增强痴呆症患者认知和情感功能的功效时，本研究开发的分析工具将是无价的。