| First Author | Zhou H | Year | 2022 |
| Journal | Sci Rep | Volume | 12 |
| Issue | 1 | Pages | 21022 |
| PubMed ID | 36471155 | Mgi Jnum | J:332036 |
| Mgi Id | MGI:7407752 | Doi | 10.1038/s41598-022-25364-2 |
| Citation | Zhou H, et al. (2022) Disruption of hippocampal neuronal circuit function depends upon behavioral state in the APP/PS1 mouse model of Alzheimer's disease. Sci Rep 12(1):21022 |
| abstractText | The Alzheimer's disease-associated peptide amyloid-beta (Abeta) has been associated with neuronal hyperactivity under anesthesia, but clinical trials of anticonvulsants or neural system suppressors have, so far, failed to improve symptoms in AD. Using simultaneous hippocampal calcium imaging and electrophysiology in freely moving mice expressing human Abeta, here we show that Abeta aggregates perturbed neural systems in a state-dependent fashion, driving neuronal hyperactivity in exploratory behavior and slow wave sleep (SWS), yet suppressing activity in quiet wakefulness (QW) and REM sleep. In exploratory behavior and REM sleep, Abeta impaired hippocampal theta-gamma phase-amplitude coupling and altered neuronal synchronization with theta. In SWS, Abeta reduced cortical slow oscillation (SO) power, the coordination of hippocampal sharp wave-ripples with both the SO and thalamocortical spindles, and the coordination of calcium transients with the sharp wave-ripple. Physostigmine improved Abeta-associated hyperactivity in exploratory behavior and hypoactivity in QW and expanded the range of gamma that coupled with theta phase, but exacerbated hypoactivity in exploratory behavior. Together, these findings show that the effects of Abeta alone on hippocampal circuit function are profoundly state dependent and suggest a reformulation of therapeutic strategies aimed at Abeta induced hyperexcitability. |
