Characterization of locus coeruleus neuronal properties with aging in two mouse models of tauopathy.

Abstract

BackgroundThe locus coeruleus (LC) is involved in the modulation of sleep and wakefulness. In humans, tau pathology develops in the LC decades before Alzheimer's disease (AD) cognitive symptoms manifest. Widespread LC degeneration is observed with disease progression; however, there is a paucity of research exploring the effect of tau pathology on the functional properties of LC neurons prior to cell death.ObjectiveTo investigate the intrinsic electrical properties of LC neurons in aged PS19 and rTg4510 tau transgenic murine models.MethodsWhole cell recordings of LC neurons were performed in two murine models of tauopathy, the PS19 and rTg4510 strains,respective age-matched wildtype (WT) littermate controls.ResultsBasic LC neuronal properties were not significantly different from WT in either PS19 or rTg4510 mice at 9 months of age, which represents a stage where AD-like symptoms are evident, and tau pathology is present in the LC. However, the resting membrane potential of LC neurons was significantly depolarized in 9-month-old PS19 transgenic mice, compared to 5-month-old PS19 transgenic mice.ConclusionsTau pathology may act to accelerate aging, contributing to hyperactivity of the LC and consequent sleep disruption in patients with tauopathy.