dc.contributor.author | Tamagnini, F | |
dc.contributor.author | Novelia, J | |
dc.contributor.author | Kerrigan, TL | |
dc.contributor.author | Brown, JT | |
dc.contributor.author | Tsaneva-Atanasova, Krasimira | |
dc.contributor.author | Randall, AD | |
dc.date.accessioned | 2015-10-16T09:46:12Z | |
dc.date.issued | 2015-10-14 | |
dc.description.abstract | Amyloidopathy involves the accumulation of insoluble amyloid b (Ab) species in the
brain’s parenchyma and is a key histopathological hallmark of Alzheimer’s disease
(AD). Work on transgenic mice that overexpress Ab suggests that elevated Ab
levels in the brain are associated with aberrant epileptiform activity and increased
intrinsic excitability (IE) of CA1 hippocampal neurons. In this study we examined if
similar changes could be observed in hippocampal CA1 pyramidal neurons from
aged PDAPP mice (20–23 month old, Indiana mutation: V717F on APP gene)
compared to their age-matched wild-type littermate controls. Whole-cell current
clamp recordings revealed that sub-threshold intrinsic properties, such as input
resistance, resting membrane potential and hyperpolarization activated “sag” were
unaffected, but capacitance was significantly decreased in the transgenic animals.
No differences between genotypes were observed in the overall number of action
potentials (AP) elicited by 500 ms supra-threshold current stimuli. PDAPP neurons,
however, exhibited higher instantaneous firing frequencies after accommodation in
response to high intensity current injections. The AP waveform was narrower
and shorter in amplitude in PDAPP mice: these changes, according to our in
silico model of a CA1/3 pyramidal neuron, depended on the respective increase
and reduction of KC and NaC voltage-gated channels maximal conductances.
Finally, the after-hyperpolarization, seen after the first AP evoked by a +300 pA
current injection and after 50 Hz AP bursts, was more pronounced in PDAPP
mice. These data show that Ab-overexpression in aged mice altered the
capacitance, the neuronal firing and the AP waveform of CA1 pyramidal neurons.
Some of these findings are consistent with previous work on younger PDAPP;
they also show important differences that can be potentially ascribed to the
interaction between amyloidopathy and ageing. Such a change of IE properties
over time underlies that the increased incidence of seizure observed in AD
patients might rely on different mechanistic pathways during progression of the
disease. | en_GB |
dc.description.sponsorship | MRC | en_GB |
dc.identifier.citation | Vol. 9, Article no. 372 | en_GB |
dc.identifier.doi | 10.3389/fncel.2015.00372 | |
dc.identifier.grantnumber | G1100623 | en_GB |
dc.identifier.uri | http://hdl.handle.net/10871/18468 | |
dc.language.iso | en | en_GB |
dc.publisher | Frontiers | en_GB |
dc.relation.url | http://journal.frontiersin.org/article/10.3389/fncel.2015.00372/abstract | en_GB |
dc.rights | This Document is Protected by copyright and was first published by Frontiers. All rights reserved. it is reproduced with permission. Copyright © 2015 Tamagnini, Novelia, Kerrigan, Brown, Tsaneva-Atanasova and Randall. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution and reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. | en_GB |
dc.subject | PDAPP | en_GB |
dc.subject | ageing | en_GB |
dc.subject | hyperexcitability | en_GB |
dc.subject | hypoexcitability | en_GB |
dc.subject | amyloidopathy | en_GB |
dc.subject | hippocampus | en_GB |
dc.subject | Alzheimer’s disease | en_GB |
dc.title | Altered intrinsic excitability of hippocampal CA1 pyramidal neurons in aged PDAPP mice | en_GB |
dc.type | Article | en_GB |
dc.date.available | 2015-10-16T09:46:12Z | |
dc.contributor.editor | Navarro-Lopez, JD | |
dc.identifier.issn | 1662-5102 | |
exeter.article-number | 372 | |
dc.description | Article | en_GB |
dc.identifier.journal | Frontiers in Cellular Neuroscience | en_GB |