| First Author | Kaczorowski CC | Year | 2011 |
| Journal | Neurobiol Aging | Volume | 32 |
| Issue | 8 | Pages | 1452-65 |
| PubMed ID | 19833411 | Mgi Jnum | J:176714 |
| Mgi Id | MGI:5292465 | Doi | 10.1016/j.neurobiolaging.2009.09.003 |
| Citation | Kaczorowski CC, et al. (2011) Mechanisms underlying basal and learning-related intrinsic excitability in a mouse model of Alzheimer's disease. Neurobiol Aging 32(8):1452-65 |
| abstractText | Accumulations of beta-amyloid (Abeta) contribute to neurological deficits associated with Alzheimer's disease (AD). The effects of Abeta 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 Abeta42 (and elevated levels of Abeta38-40) in naive 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 naive 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 Abeta 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). |
