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. ? ? ?
