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. ? ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Exploratory/Developmental Grants (R21)
Project #
1R21AG026043-01A1
Application #
7048089
Study Section
Modeling and Analysis of Biological Systems Study Section (MABS)
Program Officer
Wagster, Molly V
Project Start
2006-06-15
Project End
2008-04-30
Budget Start
2006-06-15
Budget End
2007-04-30
Support Year
1
Fiscal Year
2006
Total Cost
$180,432
Indirect Cost
Name
University of California San Francisco
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
094878337
City
San Francisco
State
CA
Country
United States
Zip Code
94143
Bonasera, Stephen J; Arikkath, Jyothi; Boska, Michael D et al. (2016) Age-related changes in cerebellar and hypothalamic function accompany non-microglial immune gene expression, altered synapse organization, and excitatory amino acid neurotransmission deficits. Aging (Albany NY) 8:2153-2181
Bonasera, Stephen J; Schenk, A Katrin; Luxenberg, Evan J et al. (2015) Mice Lacking Serotonin 2C Receptors Have increased Affective Responses to Aversive Stimuli. PLoS One 10:e0142906
Zhou, Lijun; Zhang, Jingjing; Fang, Qichen et al. (2009) Autophagy-mediated insulin receptor down-regulation contributes to endoplasmic reticulum stress-induced insulin resistance. Mol Pharmacol 76:596-603
Goulding, Evan H; Schenk, A Katrin; Juneja, Punita et al. (2008) A robust automated system elucidates mouse home cage behavioral structure. Proc Natl Acad Sci U S A 105:20575-82
Webb, Amy; Miller, Bruce; Bonasera, Stephen et al. (2008) Role of the tau gene region chromosome inversion in progressive supranuclear palsy, corticobasal degeneration, and related disorders. Arch Neurol 65:1473-8
Bonasera, Stephen J; Schenk, A Katrin; Luxenberg, Evan J et al. (2008) A novel method for automatic quantification of psychostimulant-evoked route-tracing stereotypy: application to Mus musculus. Psychopharmacology (Berl) 196:591-602