Elsevier

Neurobiology of Disease

Volume 11, Issue 3, December 2002, Pages 394-409
Neurobiology of Disease

Regular Article
Long-Term Potentiation Is Increased in the CA1 Area of the Hippocampus of APPswe/ind CRND8 Mice

https://doi.org/10.1006/nbdi.2002.0557Get rights and content

Abstract

The present study reports changes in synaptic function and plasticity [long-term potentiation (LTP)] in a recently developed mouse model of Alzheimer's disease (CRND8 line) harboring a double amyloid precursor protein mutation (APPswe/ind). In 9-week-old preplaque transgenic (Tg) mice brain slices, basal synaptic function in the hippocampal CA1 area was unchanged. Only one of three different LTP induction protocols revealed early influence of genotype on synaptic plasticity. By 20 weeks of age, there were numerous plaques in the hippocampus from Tg mice associated with more robust evidence for genotype-related effects in synaptic function. Field potential maximum slope was consistently decreased and LTP was increased, irrespective of the stimulation protocol used. In addition, there was clear evidence of increased synaptic excitability in Tg mice. Furthermore, the maximum amplitude of evoked IPSCs was decreased whereas the maximum amplitude of evoked EPSCs was increased in 20-week-old Tg mice. Collectively, these results suggest a number of APP genotype-related changes in the fine-tuning of the CA1 area circuitry, some of which are likely to contribute to the pathology-dependent effects on LTP observed in CRND8 mice.

References (50)

  • M.P. Mattson et al.

    Evidence for excitoprotective and intraneuronal calcium-regulating roles for secreted forms of the beta-amyloid precursor protein

    Neuron

    (1993)
  • M. Noda et al.

    Glutamate release from microglia via glutamate transporter is enhanced by amyloid-beta peptide

    Neuroscience

    (1999)
  • M. Pakaski et al.

    Vulnerability of small GABAergic neurons to human beta-amyloid pentapeptide

    Brain Res.

    (1998)
  • A. Parent et al.

    Synaptic transmission and hippocampal long-term potentiation in transgenic mice expressing FAD-linked presenilin 1

    Neurobiol. Dis.

    (1999)
  • Y. Perez et al.

    Differential induction of long-lasting potentiation of inhibitory postsynaptic potentials by theta patterned stimulation versus 100-Hz tetanization in hippocampal pyramidal cells in vitro

    Neuroscience

    (1999)
  • M. Sawada et al.

    Amyloid beta proteins reduce the GABA-induced Cl-current in identified Aplysia neurons

    Neurosci. Lett.

    (1996)
  • I. Schneider et al.

    Mutant presenilins disturb neuronal calcium homeostasis in the brain of transgenic mice, decreasing the threshold for excitotoxicity and facilitating long-term potentiation

    J. Biol. Chem.

    (2001)
  • G.R. Seabrook et al.

    Modulation of long-term potentiation in CA1 region of mouse hippocampal brain slices by GABAA receptor benzodiazepine site ligands

    Neuropharmacology

    (1997)
  • G.R. Seabrook et al.

    Transgenic animals relevant to Alzheimer's disease

    Neuropharmacology

    (1999)
  • G.R. Seabrook et al.

    Mechanisms contributing to the deficits in hippocampal synaptic plasticity in mice lacking amyloid precursor protein

    Neuropharmacology

    (1999)
  • J. Wu et al.

    Beta-amyloid-(1–40) increases long-term potentiation in rat hippocampus in vitro

    Eur. J. Pharmacol.

    (1995)
  • L. Ye et al.

    Suppressive action produced by beta-amyloid peptide fragment 31–35 on long-term potentiation in rat hippocampus is N-methyl-d-aspartate receptor-independent: It's offset by (−)huperzine A

    Neurosci. Lett.

    (1999)
  • S.H. Zaman et al.

    Enhanced synaptic potentiation in transgenic mice expressing presenilin 1 familial Alzheimer's disease mutation is normalized with a benzodiazepine

    Neurobiol. Dis.

    (2000)
  • C. Arias et al.

    Beta-amyloid peptide fragment 25–35 potentiates the calcium-dependent release of excitatory amino acids from depolarized hippocampal slices

    J. Neurosci. Res.

    (1995)
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    1

    To whom correspondence should be addressed. Fax: (908)740-3294. E-mail: [email protected].

    2

    These two authors contributed equally to this work.

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