We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Altered Cortical and Hippocampal Excitability in TgF344-AD Rats Modeling Alzheimer's Disease Pathology.
- Authors
Stoiljkovic, Milan; Kelley, Craig; Stutz, Bernardo; Horvath, Tamas L; Hajós, Mihály
- Abstract
Current findings suggest that accumulation of amyloid-β (Aβ) and hyperphosphorylated tau in the brain disrupt synaptic function in hippocampal–cortical neuronal networks leading to impairment in cognitive and affective functions in Alzheimer's disease (AD). Development of new disease-modifying AD drugs are challenging due to the lack of predictive animal models and efficacy assays. In the present study we recorded neural activity in TgF344-AD rats, a transgenic model with a full array of AD pathological features, including age-dependent Aβ accumulation, tauopathy, neuronal loss, and cognitive impairments. Under urethane anesthesia, TgF344-AD rats showed significant age-dependent decline in brainstem-elicited hippocampal theta oscillation and decreased theta-phase gamma-amplitude coupling comparing to their age-matched wild-type counterparts. In freely-behaving condition, the power of hippocampal theta oscillation and gamma power during sharp-wave ripples were significantly lower in TgF344-AD rats. Additionally, these rats showed impaired coherence in both intercortical and hippocampal–cortical network dynamics, and increased incidence of paroxysmal high-voltage spindles, which occur during awake, behaviorally quiescent state. TgF344-AD rats demonstrated impairments in sensory processing, having diminished auditory gating and 40-Hz auditory evoked steady-state response. The observed differences in neurophysiological activities in TgF344-AD rats, which mirror several abnormalities described in AD patients, may be used as promising markers to monitor disease-modifying therapies.
- Publication
Cerebral Cortex, 2019, Vol 29, Issue 6, p2716
- ISSN
1047-3211
- Publication type
Article
- DOI
10.1093/cercor/bhy140