Age-dependent disruption in hippocampal θ oscillation in amyloid-β overproducing transgenic mice.
Transgenic mice are used to model increased brain amyloid-β (Aβ) and amyloid plaque formation reflecting Alzheimer's disease pathology. In our study hippocampal network oscillations, population spikes, and long-term potentiation (LTP) were recorded in APPswe/PS1dE9 (APP/PS1) and presenilin1 (PS1) transgenic and wild type mice at 2, 4, and 8 months of age under urethane anesthesia. Hippocampal theta oscillations elicited by brainstem stimulation were similar in wild type and PS1 mice at all age groups. In contrast, APP/PS1 mice showed an age-dependent decrease in hippocampal activity, characterized by a significant decline in elicited theta power and frequency at 4 and 8 months. Magnitudes of population spikes and long-term potentiation in the dentate gyrus were similar across groups at both 4 and 8 months. In APP/PS1 mice, soluble and insoluble Aβ, and hippocampal and cortical plaque load increased with age, and the disruption in hippocampal theta oscillation showed a significant correlation with plaque load. Our study shows that, using in vivo electrophysiological methods, early Aβ-related functional deficits can be robustly detected in the brainstem-hippocampus multisynaptic network.
Pfizer Global Research and Development, Groton, CT, USA.
Liam
L
Scott
Jianlin
J
Feng
Tamás
T
Kiss
Elie
E
Needle
Kevin
K
Atchison
Thomas T
TT
Kawabe
Anthony J
AJ
Milici
Eva
E
Hajós-Korcsok
David
D
Riddell
Mihály
M
Hajós
D000375:Aging / Q000235:genetics* / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000096:biosynthesis* / Q000235:genetics*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics; D000818:Animals; D006624:Hippocampus / Q000502:physiology*; D017774:Long-Term Potentiation / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D053764:Presenilin-1 / Q000235:genetics; D013826:Theta Rhythm / Q000502:physiology*
D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D053764:Presenilin-1