Mechanisms underlying basal and learning-related intrinsic excitability in a mouse model of Alzheimer's disease

C. C. Kaczorowski*, E. Sametsky, S. Shah, R. Vassar, J. F. Disterhoft

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

79 Scopus citations


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 languageEnglish (US)
Pages (from-to)1452-1465
Number of pages14
JournalNeurobiology of Aging
Issue number8
StatePublished - Aug 2011


  • 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


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