<p class="first" id="P1">Disruption of circadian rhythms is commonly reported in individuals
with Alzheimer’s
disease (AD). Neurons in the primary circadian pacemaker, the suprachiasmatic nucleus
(SCN), exhibit daily rhythms in spontaneous neuronal activity which are important
for maintaining circadian behavioral rhythms. Disruption of SCN neuronal activity
has been reported in animal models of other neurodegenerative disorders; however,
the effect of AD on SCN neurophysiology remains unknown. In this study we examined
circadian behavioral and electrophysiological changes in a mouse model of AD, using
male mice from the Tg-SwDI line which expresses human amyloid precursor protein with
the familial Swedish (K670N/M671L), Dutch (E693Q), Iowa (D694N) mutations. The free-running
period of wheel-running behavior was significantly shorter in Tg-SwDI mice compared
to wild-type (WT) controls at all ages examined (3, 6, and 10 months). At the SCN
level, the day/night difference in spike rate was significantly dampened in 6–8 month-old
Tg-SwDI mice, with decreased AP firing during the day and an increase in neuronal
activity at night. The dampening of SCN excitability rhythms in Tg-SwDI mice was not
associated with changes in input resistance, resting membrane potential, or action
potential afterhyperpolarization amplitude; however, SCN neurons from Tg-SwDI mice
had significantly reduced A-type potassium current (I
<sub>A</sub>) during the day compared to WT cells. Taken together, these results provide
the first
evidence of SCN neurophysiological disruption in a mouse model of AD, and highlight
I
<sub>A</sub> as a potential target for AD treatment strategies in the future.
</p>