Information theoretic assays of exploration in aged mice

描述（由申请人提供）：正常的衰老伴随着认知和情感功能的改变。虽然这些变化在其他方面健康的老年人中意义不大，但它们可能对患有痴呆症或认知障碍的人产生毁灭性影响。不幸的是，目前对老年人行为障碍背后的基本神经科学知识仍然知之甚少。老年小鼠是解决这一重大缺陷的合适模型。衰老的老鼠大脑的神经生理学与人类相似，在老鼠身上观察到的许多行为也与人类相似。例如，在老鼠和人类中，对新环境的总体探索都有年龄相关的下降。探索行为由不同的神经递质系统以特定的方式调节；因此，对探索行为的复杂分析可以为研究与年龄相关的中枢神经系统功能变化提供重要的见解。目前，缺乏研究探索性行为的有力工具；我们建议开发这些工具。我们将开发一种多行为状态（MBS）表征竞技场对小鼠定位、小鼠运动活动（停止/暂停、转弯和前进）和其他小鼠行为学参数（饲养、伸展、梳理等）的影响。然后，我们将扩展这种方法来研究位置记忆的获取如何改变MBS模型中的变量。将计算这些数据的熵率和预测信息，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（bb0 - 24个月）C57BI6小鼠队列中收集。我们的初步结果表明，与年轻一代相比，老年小鼠具有较少复杂的新环境探索模式。本研究开发的分析工具在评估未来以药理学或遗传学为基础的治疗方法以增强痴呆症患者的认知和情感功能的有效性时将是无价的。

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.