Intrinsic excitability changes induced by acute treatment of hippocampal CA1 pyramidal neurons with exogenous Amyloid β peptide.
© 2014 Wiley Periodicals, Inc.
Reason for embargo
Accumulation of Aβ peptides in the human brain is a canonical pathological hallmark of Alzheimer's disease (AD). Recent work in Aβ-overexpressing transgenic mice indicates that elevated brain Aβ levels can be associated with aberrant epileptiform activity. In line with this, such mice can also exhibit altered intrinsic excitability (IE) of cortical and hippocampal neurons: these observations may relate to the increased prevalence of seizures in AD patients. In this study we examined what changes in IE are produced in hippocampal CA1 pyramidal cells following 2-5 hours treatment with an oligomeric preparation of synthetic human Aβ1-42 peptide. Whole cell current clamp recordings were compared between Aβ-(500nM) and vehicle-(DMSO 0.05%) treated hippocampal slices obtained from mice. The soluble Aβ treatment did not produce alterations in sub-threshold intrinsic properties including membrane potential, input resistance and hyperpolarization activated "sag". Similarly, no changes were noted in the firing profile evoked by 500 ms square current supra-threshold stimuli. However, Aβ 500nM treatment resulted in the hyperpolarization of the action potential (AP) threshold. In addition, treatment with Aβ at 500nM depressed the after-hyperpolarization (AHP) that followed both a 1 single AP or 50Hz trains of between 5 and 25 APs. These data suggest that acute exposure to soluble Aβ oligomers affects IE properties of CA1 pyramidal neurons differently from outcomes seen in transgenic models of amyloidopathy. However, in both chronic and acute models the IE changes are towards hyper-excitability, reinforcing the idea that amyloidopathy and increased incidence in seizures might be causally related in AD patients. This article is protected by copyright. All rights reserved.
This is the accepted version of the article, which has been published in final form at DOI: 10.1002/hipo.22403
Vol. 25 (7), pp. 786-797