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Title: | Evoked Cortical Depolarizations Before and After the Amyloid Plaque Accumulation: Voltage Imaging Study | Authors: | Zhu, MH. Jogdand, AH. Jang, J. Nagella, SC. Das, B. Milošević, MM. Yan, R. Antic, SD. |
Keywords: | APP/PS1;Alzheimer’s disease;Amyloid plaque;Excitability;Synaptic dysfunction | Issue Date: | 16-Aug-2022 | Rank: | M22 | Publisher: | National Library of Medicine | Journal: | J Alzheimers Dis. | Volume: | 88 | Issue: | 4 | Start page: | 1443 | End page: | 1458 | Abstract: | Background:In Alzheimer’s disease (AD), synaptic dysfunction is thought to occur many years before the onset of cognitive decline. Objective:Detecting synaptic dysfunctions at the earliest stage of AD would be desirable in both clinic and research settings. Methods:Population voltage imaging allows monitoring of synaptic depolarizations, to which calcium imaging is relatively blind. We developed an AD mouse model (APPswe/PS1dE9 background) expressing a genetically-encoded voltage indicator (GEVI) in the neocortex. GEVI was restricted to the excitatory pyramidal neurons (unlike the voltage-sensitive dyes). Results:Expression of GEVI did not disrupt AD model formation of amyloid plaques. GEVI expression was stable in both AD model mice and Control (healthy) littermates (CTRL) over 247 days postnatal. Brain slices were stimulated in layer 2/3. From the evoked voltage waveforms, we extracted several parameters for comparison AD versus CTRL. Some parameters (e.g., temporal summation, refractoriness, and peak latency) were weak predictors, while other parameters (e.g., signal amplitude, attenuation with distance, and duration (half-width) of the evoked transients) were stronger predictors of the AD condition. Around postnatal age 150 days (P150) and especially at P200, synaptically-evoked voltage signals in brain slices were weaker in the AD groups versus the age- and sex-matched CTRL groups, suggesting an AD-mediated synaptic weakening that coincides with the accumulation of plaques. However, at the youngest ages examined, P40 and P80, the AD groups showed differentially stronger signals, suggesting “hyperexcitability” prior to the formation of plaques. Conclusion:Our results indicate bidirectional alterations in cortical physiology in AD model mice; occurring both prior (P40-80), and after (P150-200) the amyloid deposition. |
URI: | https://biore.bio.bg.ac.rs/handle/123456789/5030 | ISSN: | 2274-5807 | DOI: | 10.3233/JAD-220249 |
Appears in Collections: | Journal Article |
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