Long-term potentiation is increased in the CA1 area of the hippocampus of APP(swe/ind) CRND8 mice.
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 (APP(swe/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.
Jolas
Thierry
T
CNS/CV Research, Schering-Plough Research Institute, 2015 Galloping Hill Road, Kenilworth, New Jersey 07033, USA. thierry.jolas@spcorp.com
Zhang
Xue-Song
XS
Zhang
Qi
Q
Wong
Gwendolyn
G
Del Vecchio
Robert
R
Gold
Lisa
L
Priestley
Tony
T
D000375:Aging; D000544:Alzheimer Disease / Q000503:physiopathology*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics; D000818:Animals; D004195:Disease Models, Animal; D004594:Electrophysiology; D019706:Excitatory Postsynaptic Potentials; D005455:Fluorescent Antibody Technique; D005838:Genotype; D018698:Glutamic Acid; D006624:Hippocampus / Q000503:physiopathology*; D017774:Long-Term Potentiation; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009154:Mutation; D009433:Neural Inhibition; D009473:Neuronal Plasticity; D058225:Plaque, Amyloid; D009435:Synaptic Transmission; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D016564:Amyloid beta-Protein Precursor; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid