Pathophysiology in the suprachiasmatic nucleus in mouse models of Huntington's disease

Journal of Neuroscience Research
Dika KuljisChristopher S Colwell

Abstract

Disturbances in sleep/wake cycle are a common complaint of individuals with Huntington's disease (HD) and are displayed by HD mouse models. The underlying mechanisms, including the possible role of the circadian timing system, are not well established. The BACHD mouse model of HD exhibits disrupted behavioral and physiological rhythms, including decreased electrical activity in the central circadian clock (suprachiasmatic nucleus, SCN). In this study, electrophysiological techniques were used to explore the ionic underpinning of the reduced spontaneous neural activity in male mice. We found that SCN neural activity rhythms were lost early in the disease progression and was accompanied by loss of the normal daily variation in resting membrane potential in the mutant SCN neurons. The low neural activity could be transiently reversed by direct current injection or application of exogenous N-methyl-d-aspartate (NMDA) thus demonstrating that the neurons have the capacity to discharge at WT levels. Exploring the potassium currents known to regulate the electrical activity of SCN neurons, our most striking finding was that these cells in the mutants exhibited an enhancement in the large-conductance calcium activated K+ (BK) currents. ...Continue Reading

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Citations

Jul 31, 2019·Journal of Neuroscience Research·Benjamin SmarrChristopher S Colwell
Mar 13, 2020·Physiological Reviews·Jenna R M HarveyAndrea L Meredith
Mar 28, 2019·Neurotherapeutics : the Journal of the American Society for Experimental NeuroTherapeutics·Magali CabanasYoon H Cho
Feb 1, 2021·Experimental Gerontology·Fabian-Xosé FernandezDavid C Negelspach
May 7, 2021·Proceedings of the National Academy of Sciences of the United States of America·Foteini ParaskevopoulouFerah Yildirim
May 13, 2021·Ageing Research Reviews·Chia-Lung Chuang, Fabio Demontis

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