Disrupted neural correlates of anesthesia and sleep reveal early circuit dysfunctions in Alzheimer models

Alzheimer’s disease (AD) begins with a decades-long presymptomatic phase, well before the onset of memory decline and global disturbances in sleep architecture. Does hippocampal circuit activity and its homeostasis change at these early stages, and does that occur in particular behavioral states? A collaborative study with the lab of Inna Slutsky combines electrophysiology and calcium imaging to establish that familial AD (fAD) model mice do not show abnormalities in CA1 firing rates during wakefulness, but CA1 hyperexcitability is clearly evident in low-arousal states of NREM sleep and anesthesia, well before memory impairments or global sleep EEG impairments can be observed. This hyperexcitability is associated with disrupted homeostatic down-regulation of CA1 mean firing rates, and spikes in field potentials that resemble epileptiform interictal discharges.