Scientific article

"Ectopic" theta oscillations and interictal activity during slow-wave state in the R6/1 mouse model of Huntington's disease

Published inNeurobiology of Disease, vol. 48, no. 3, p. 409-417
Publication date2012

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.

  • Animals
  • Disease Models, Animal
  • Electroencephalography
  • Hippocampus/physiopathology
  • Huntington Disease/physiopathology
  • Mice
  • Mice, Transgenic
  • Neocortex/physiopathology
  • Neural Pathways/physiopathology
Affiliation Not a UNIGE publication
Citation (ISO format)
PIGNATELLI, Michele et al. ‘Ectopic’ theta oscillations and interictal activity during slow-wave state in the R6/1 mouse model of Huntington’s disease. In: Neurobiology of Disease, 2012, vol. 48, n° 3, p. 409–417. doi: 10.1016/j.nbd.2012.07.015
Main files (1)
Article (Published version)
ISSN of the journal0969-9961

Technical informations

Creation07/08/2020 1:00:00 PM
First validation07/08/2020 1:00:00 PM
Update time03/15/2023 10:34:38 PM
Status update03/15/2023 10:34:37 PM
Last indexation10/19/2023 1:29:55 PM
All rights reserved by Archive ouverte UNIGE and the University of GenevaunigeBlack