Enhancing GABAergic signaling ameliorates aberrant gamma oscillations of olfactory bulb in AD mouse models

作者：Ming Chen, Yunan Chen, Qingwei Huo, Lei Wang, Shuyi Tan, Afzal Misrani, Jinxiang Jiang, Jian Chen, Shiyuan Chen, Jiawei Zhang, Sidra Tabassum, Jichen Wang, Xi Chen, Cheng Long, Li Yang · 发表于：Molecular Neurodegeneration · 年份：2021 · DOI：10.1186/s13024-021-00434-7 · 被引用次数：59 · 研究领域：Olfactory and Sensory Function Studies、Neurogenesis and neuroplasticity mechanisms、Memory and Neural Mechanisms

Abstract Background Before the deposition of amyloid-beta plaques and the onset of learning memory deficits, patients with Alzheimer’s disease (AD) experience olfactory dysfunction, typified by a reduced ability to detect, discriminate, and identify odors. Rodent models of AD, such as the Tg2576 and APP/PS1 mice, also display impaired olfaction, accompanied by aberrant in vivo or in vitro gamma rhythms in the olfactory pathway. However, the mechanistic relationships between the electrophysiological, biochemical and behavioral phenomena remain unclear. Methods To address the above issues in AD models, we conducted in vivo measurement of local field potential (LFP) with a combination of in vitro electro-olfactogram (EOG), whole-cell patch and field recordings to evaluate oscillatory and synaptic function and pharmacological regulation in the olfactory pathway, particularly in the olfactory bulb (OB). Levels of protein involved in excitation and inhibition of the OB were investigated by western blotting and fluorescence staining, while behavioral studies assessed olfaction and memory function. Results LFP measurements demonstrated an increase in gamma oscillations in the OB accompanied by altered olfactory behavior in both APP/PS1 and 3xTg mice at 3–5 months old, i.e. an age before the onset of plaque formation. Fewer olfactory sensory neurons (OSNs) and a reduced EOG contributed to a decrease in the excitatory responses of M/T cells, suggesting a decreased ability of M/T cells ...