Abstract
Accumulations of β-amyloid (Aβ) contribute to neurological deficits associated with Alzheimer's disease (AD). The effects of Aβ on basal neuronal excitability and learning-related AHP plasticity were examined using whole-cell recordings from hippocampal neurons in the 5XFAD mouse model of AD. A robust increase in Aβ42 (and elevated levels of Aβ38-40) in naïve 5XFAD mice was associated with decreased basal neuronal excitability, evidenced by a select increase in Ca 2+-sensitive afterhyperpolarization (AHP). Moreover, trace fear deficits observed in a subset of 5XFAD weak-learner mice were associated with a greater enhancement of the AHP in neurons, as compared to age-matched 5XFAD learner and 5XFAD naïve mice. Importantly, learning-related plasticity of the AHP remained intact in a subset of 5XFAD mice that learned trace fear conditioning to a set criterion. We show that APP-PS1 mutations enhance Aβ and disrupt basal excitability via a Ca 2+-dependent enhancement of the AHP, and suggest disruption to learning-related modulation of intrinsic excitability resulted, in part, from altered cholinergic modulation of the AHP in the 5XFAD mouse model of AD (170 of 170).
| Original language | English (US) |
|---|---|
| Pages (from-to) | 1452-1465 |
| Number of pages | 14 |
| Journal | Neurobiology of Aging |
| Volume | 32 |
| Issue number | 8 |
| DOIs | |
| State | Published - Aug 2011 |
Funding
The authors wish to thank Caroline Cook who provided advice on the illustrations. This work was supported by the National Institutes of Mental Health grant F31 MH-067445 awarded to C.C.K., and National Institutes of Health grants R37 AG-08796 and T32 AG20506 awarded to J.F.D.
Keywords
- AD
- AHP
- Afterhyperpolarization
- Aging
- Alzheimer's disease
- CA1
- Fear conditioning
- Hippocampus
- Intrinsic excitability
- Intrinsic plasticity
- Trace fear conditioning
ASJC Scopus subject areas
- Clinical Neurology
- Geriatrics and Gerontology
- Aging
- General Neuroscience
- Developmental Biology