Synaptic dysfunction in hippocampus of transgenic mouse models of Alzheimer's disease: A multi-electrode array study

Seon Ah Chong, Iryna Benilova, Hamdy Shaban, Bart De Strooper, Herman Devijver, Dieder Moechars, Wolfgang Eberle, Carmen Bartic, Fred Van Leuven, Geert Callewaert

Research output: Contribution to journalArticlepeer-review

46 Citations (Scopus)

Abstract

APP.V717I and Tau.P301L transgenic mice develop Alzheimer's disease pathology comprising important aspects of human disease including increased levels of amyloid peptides, cognitive and motor impairment, amyloid plaques and neurofibrillary tangles. The combined model, APP.V717I × Tau.P301L bigenic mice (biAT mice) exhibit aggravated amyloid and tau pathology with severe cognitive and behavioral defects. In the present study, we investigated early changes in synaptic function in the CA1 and CA3 regions of acute hippocampal slices of young APP.V717I, Tau.P301L and biAT transgenic animals. We have used planar multi-electrode arrays (MEA) and improved methods for simultaneous multi-site recordings from two hippocampal sub-regions. In the CA1 region, long-term potentiation (LTP) was severely impaired in all transgenic animals when compared with age-matched wild-type controls, while basal synaptic transmission and paired-pulse facilitation were minimally affected. In the CA3 region, LTP was normal in Tau.P301L and APP.V717I but clearly impaired in biAT mice. Surprisingly, frequency facilitation in CA3 was significantly enhanced in Tau.P301L mice, while not affected in APP.V717I mice and depressed in biAT mice. The findings demonstrate important synaptic changes that differ considerably in the hippocampal sub-regions already at young age, well before the typical amyloid or tau pathology is evident.

Original languageEnglish
Pages (from-to)284-291
Number of pages8
JournalNeurobiology of Disease
Volume44
Issue number3
DOIs
Publication statusPublished - Dec 2011

Keywords

  • AD transgenic mice
  • Amyloid
  • Dual recordings
  • Hippocampal slices
  • Multi-electrode arrays
  • Synaptic dysfunction
  • Tau

ASJC Scopus subject areas

  • Neurology

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