Amyloid-beta1-42 reduces neuronal excitability in mouse dentate gyrus.
Amyloid-beta (Abeta) is causally implicated in Alzheimer's disease and neuroplasticity failure has acquired validity as a possible mechanism of early AD pathogenesis. We have previously demonstrated that oligomeric Abeta(1-42) inhibits LTP in the dentate gyrus of rat hippocampal slices. We now show, using whole cell recordings in hippocampal granule cells, that oligomeric Abeta(1-42) decreases neuronal excitability. In particular, Abeta(1-42) application was associated with a decrease in the number of action potentials fired in response to current injection, and with an increase in the amplitude of the afterhyperpolarization. Reduced excitability may underlie the Abeta-mediated impairment in neuroplasticity, and ultimately may contribute to the memory loss in Alzheimer disease.
Yun
Sung Hwan
SH
Department of Pediatrics and Neurology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60614, USA.
Gamkrelidze
Georgi
G
Stine
W Blaine
WB
Sullivan
Patrick M
PM
Pasternak
Joseph F
JF
Ladu
Mary Jo
MJ
Trommer
Barbara L
BL
D000200:Action Potentials; D016229:Amyloid beta-Peptides / Q000494:pharmacology / Q000502:physiology*; D000818:Animals; D001704:Biopolymers; D018891:Dentate Gyrus / Q000187:drug effects / Q000502:physiology*; D066298:In Vitro Techniques; D017774:Long-Term Potentiation; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D018408:Patch-Clamp Techniques; D010446:Peptide Fragments / Q000494:pharmacology / Q000502:physiology*
D016229:Amyloid beta-Peptides; D001704:Biopolymers; D010446:Peptide Fragments; C078592:amyloid beta-protein (1-40)