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 A ) during the day compared to WT cells. 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 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). 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. 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. 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. Paul, Jodi R Munir, Hira A van Groen, Thomas Gamble, Karen Lĭisruption of circadian rhythms is commonly reported in individuals with Alzheimer's disease (AD). Since neither propagation of single PSPs nor integration of multiple PSPs (pattern recognition) changes in TG neurons, we conclude that ADīehavioral and SCN neurophysiological disruption in the Tg-SwDI mouse model of Alzheimer's disease. Our simulations predict the way how subthreshold dendritic signaling and pattern recognition are preserved in TG neurons: amyloid-related membrane alterations compensate for the pathological effects that dendritic atrophy has on subthreshold dendritic signal transfer and integration in layer II/III somatosensory neurons of this hAPP mouse model for AD. Synaptic input pattern recognition ability was also predicted to be unaltered in TG neurons in two different soma-dendritic membrane models investigated. Despite the widespread dendritic degeneration and membrane alterations in mutant mouse neurons, surprisingly little, or no change was detected in steady-state and 50 Hz sinusoidal voltage transfers, current transfers, and local and propagation delays of PSPs traveling along dendrites of TG neurons. Local synaptic activities were simulated in various points of the dendritic arbors and properties of subthreshold dendritic impulse propagation and predictors of synaptic input pattern recognition ability were quantified and compared in modeled WT and TG neurons. In this study spatial reconstructions and electrophysiological measurements of layer II/III pyramidal neurons of the somatosensory cortex from wild-type (WT) and transgenic ( TG) human amyloid precursor protein (hAPP) overexpressing Tg2576 mice were used to build faithful segmental cable models of these neurons. However, little effort has been made to study the potential effects of combined morphological and membrane alterations on signal transfer and synaptic integration in neurons that build up affected neural networks in AD. Amyloid-related dendritic atrophy and membrane alterations of susceptible brain neurons in AD, and in animal models of AD are widely recognized. One century after its first description, pathology of Alzheimer's disease (AD) is still poorly understood. Somogyi, Attila Katonai, Zoltán Alpár, Alán Wolf, Ervin A Novel Form of Compensation in the Tg2576 Amyloid Mouse Model of Alzheimer's Disease.
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