Intrinsic excitability changes induced by acute treatment of hippocampal CA1 pyramidal neurons with exogenous amyloid β peptide. Issue 7 (25th March 2015)

• Record Type: Journal Article
• Authors: Tamagnini, Francesco; Scullion, Sarah; Brown, Jon T.; Randall, Andrew D.
• Is Part Of: Hippocampus. Volume 25:Issue 7(2015:Jul.)
• Page Start: 786
• Page End: 797
• Publication Date: 2015-03-25
• Subjects: Hippocampus (Brain) -- Periodicals; 612.825
• DOI: 10.1002/hipo.22403
• Languages: English
• ISSNs: 1050-9631

Abstract

<abstract abstract-type="main"> <title>ABSTRACT</title> <p>Accumulation of beta‐amyloid (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 increased 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 after 2–5 h treatment with an oligomeric preparation of synthetic human Aβ 1–42 peptide. Whole cell current clamp recordings were compared between Aβ‐(500 n<italic>M</italic>) 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 n<italic>M</italic> treatment resulted in the hyperpolarization of the action potential (AP) threshold. In addition, treatment with Aβ at 500 n<italic>M</italic> depressed the after‐hyperpolarization that followed both a single AP or 50 Hz trains of a number of APs between 5 and 25. 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 toward hyperexcitability, reinforcing the idea that amyloidopathy and increased incidence in seizures might be causally related in AD patients. © 2014 The Authors Hippocampus Published by Wiley Periodicals, Inc.</p> </abstract>