A study of long-term potentiation in transgenic mice over-expressing mutant forms of both amyloid precursor protein and presenilin-1.
Synaptic transmission and long-term potentiation (LTP) in the CA1 region of hippocampal slices have been studied during ageing of a double transgenic mouse strain relevant to early-onset familial Alzheimer's disease (AD). This strain, which over-expresses both the 695 amino acid isoform of human amyloid precursor protein (APP) with K670N and M671L mutations and presenilin 1 with the A246E mutation, has accelerated amyloidosis and plaque formation. There was a decrease in synaptic transmission in both wildtype and transgenic mice between 2 and 9 months of age. However, preparing slices from 14 month old animals in kynurenic acid (1 mM) counteracted this age-related deficit. Basal transmission and paired-pulse facilitation was similar between the two groups at all ages (2, 6, 9 and 14 months) tested. Similarly, at all ages LTP, induced either by theta burst stimulation or by multiple tetani, was normal. These data show that a prolonged, substantially elevated level of Abeta are not sufficient to cause deficits in the induction or expression of LTP in the CA1 hippocampal region.
Fitzjohn
Stephen M
SM
MRC Centre for Synaptic Plasticity, Department of Anatomy, University of Bristol, UK. stephen.fitzjohn@bris.ac.uk
Kuenzi
Frederick
F
Morton
Robin A
RA
Rosahl
Thomas W
TW
Lewis
Huw
H
Smith
David
D
Seabrook
Guy R
GR
Collingridge
Graham L
GL
D000375:Aging / Q000473:pathology; D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D056547:CA1 Region, Hippocampal / Q000503:physiopathology; D004558:Electric Stimulation; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology; D006801:Humans; D017774:Long-Term Potentiation / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic; D050505:Mutant Proteins / Q000235:genetics / Q000378:metabolism*; D058225:Plaque, Amyloid / Q000378:metabolism / Q000473:pathology; D053764:Presenilin-1 / Q000235:genetics / Q000378:metabolism*; D009435:Synaptic Transmission / Q000502:physiology; D013746:Tetany / Q000503:physiopathology
D016564:Amyloid beta-Protein Precursor; D050505:Mutant Proteins; D053764:Presenilin-1