Altered slow (<1 Hz) and fast (beta and gamma) neocortical oscillations in the 3xTg-AD mouse model of Alzheimer's disease under anesthesia

Abstract

The 3xTg-AD mouse model reproduces the main features associated with the etiology of familial Alzheimer's disease (AD). To investigate whether these features imply functional cortical network alterations and their evolution with age, we studied spontaneous slow oscillations, activity that integrates cellular and network properties. We quantified different parameters of the emergent slow oscillations—alternating Up and Down states—and of the embedded beta-gamma rhythms of 3xTg-AD and wild-type mice at 7 and 20 months of age. Most group differences occurred at 20 months of age: 3xTg-AD mice presented lower oscillatory frequency, higher cycle variability, and reduced relative (Up/Down) firing rate with respect to controls. The high-frequency analysis revealed a shift toward lower frequencies in older 3xTg-AD animals, reminiscent of one of the electroencephalography hallmarks of patients with AD. This first systematic characterization of the cortical emergent rhythms in 3xTg-AD strain provides insights into the network mechanisms underlying associated network activity alterations.