« Ectopic » theta oscillations and interictal activity during slow-wave state in the R6/1 mouse model of Huntington’s disease
Neurobiology of Disease. 2012-12-01; 48(3): 409-417
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1. Neurobiol Dis. 2012 Dec;48(3):409-17. doi: 10.1016/j.nbd.2012.07.015. Epub 2012
« Ectopic » theta oscillations and interictal activity during slow-wave state in
the R6/1 mouse model of Huntington’s disease.
Pignatelli M(1), Lebreton F, Cho YH, Leinekugel X.
(1)Université de Bordeaux, Institut des Maladies Neurodégénératives, UMR 5293,
F-33000 Bordeaux, France.
The pathophysiology of Huntington’s disease (HD) is primarily associated with
striatal degeneration and a number of behavioral symptoms such as involuntary
movements, cognitive decline, psychiatric disorders, and in the most
juvenile-onset cases with epilepsy. In addition to several changes in cellular
and synaptic properties previously reported in HD, attention was recently driven
towards the potential relationships between cognitive deficits and sleep
disturbances in patients and animal models of Huntington’s disease. In the
present study, we have investigated whether the population-activity patterns
normally expressed by the hippocampal and neocortical circuits during active and
slow-wave states are affected in R6/1 mice, a model of Huntington’s disease. By
performing electrophysiological recordings from the hippocampus and neocortex of
R6/1 mice that were either freely moving, head restrained or anesthetized, we
observed an altered segregation of active and slow wave brain states, in relation
with an epileptic phenotype. Slow-wave state (SWS) in R6/1 was characterized by
the intrusion of active-state features (increased 6-10 Hz theta power and
depressed 2-3 Hz delta power) and transient, temporally misplaced (« ectopic »)
theta oscillations. The epileptic phenotype, in addition to previously reported
occasional ictal seizures, was characterized by the systematic presence of
interictal activity, confined to SWS. Ectopic theta episodes, which could be
reversed by the cholinergic antagonist atropine, concentrated interictal spikes
and phase-locked hippocampal sharp-wave-ripples. These results point to major
alterations of neuronal activity during rest in R6/1 mice, potentially involving
anomalous activation of the cholinergic system, which may contribute to the
cognitive deficits observed in Huntington’s disease.
Copyright © 2012 Elsevier Inc. All rights reserved.
PMID: 22842017 [Indexed for MEDLINE]