Intrinsic excitability changes induced by acute treatment of hippocampal CA1 pyramidal neurons with exogenous amyloid β peptide

Tamagnini, F. ORCID: https://orcid.org/0000-0002-8741-5094, Scullion, S., Brown, J. T. and Randall, A. D. (2015) Intrinsic excitability changes induced by acute treatment of hippocampal CA1 pyramidal neurons with exogenous amyloid β peptide. Hippocampus, 25 (7). pp. 786-797. ISSN 1050-9631 doi: 10.1002/hipo.22403

Abstract/Summary

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-(500 nM) 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 500 nM treatment resulted in the hyperpolarization of the action potential (AP) threshold. In addition, treatment with Aβ at 500 nM 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.

Item Type	Article
URI	https://reading-clone.eprints-hosting.org/id/eprint/80569
Identification Number/DOI	10.1002/hipo.22403
Refereed	Yes
Divisions	Life Sciences > School of Chemistry, Food and Pharmacy > School of Pharmacy > Division of Pharmacology
Publisher	Wiley
Download/View statistics	View download statistics for this item