Changes in learning and memory (L&M) occur with aging, but little is known about their underlying molecular and cellular causes. Mice show age-related social transmission of food preference (STFP), and contextual conditioning. Remarkably, a mull mutation of the K+ channel auxiliary subunit Kvbeta1.1 improves L&M in these tasks, specifically in aged mice. In contrast, this mutation either impaired or had no effect in the performance of young mice in these tasks. Consistent with the hypothesis that an increased slow after-hyperpolarization (sAHP) contributes to age- related L&M deficits, the sAHO of the aged Kvbeta1.1 mutants is comparable to that of young wild type (WT) mice, but significantly smaller than aged Wts.
The specific aims of this proposal are: To further characterize the behavioral determinants underlying the rescue of L&M in aged Kvbeta1.1-/- mutant mice. To determine the time course for the L&M improvements triggered by the Kvbeta1.1.-/- mutation. To identify the electrophysiological mechanisms underlying the rescue of hippocampal-dependent L&M in the Kvbeta1.12.-/- mutants. To derive mice with neural specific and inducible mutations of Kvbeta1.1. The studies proposed here will not only further our understanding of the role of kvbeta1.1. in age-dependent L&M, but they will also be crucial for developing strategies to overcome these L&M impairments. Additionally, these studies will further our understanding of the possible connections between sAHP, LTP and L&M.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Project (R01)
Project #
5R01AG017499-04
Application #
6629862
Study Section
Special Emphasis Panel (ZRG1-IFCN-3 (04))
Program Officer
Wagster, Molly V
Project Start
2000-03-01
Project End
2005-02-28
Budget Start
2003-03-15
Budget End
2004-02-29
Support Year
4
Fiscal Year
2003
Total Cost
$296,419
Indirect Cost
Name
University of California Los Angeles
Department
Neurosciences
Type
Schools of Medicine
DUNS #
092530369
City
Los Angeles
State
CA
Country
United States
Zip Code
90095
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Murphy, Geoffrey G; Fedorov, Nikolai B; Giese, K Peter et al. (2004) Increased neuronal excitability, synaptic plasticity, and learning in aged Kvbeta1.1 knockout mice. Curr Biol 14:1907-15
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