帕尔瓦布明
光遗传学
神经科学
前额叶皮质
心理学
疾病
兴奋性突触后电位
抑制性突触后电位
电生理学
医学
认知
内科学
作者
Shu Shu,Siyi Xu,Lei Ye,Yi Liu,Xiang Cao,Junqiu Jia,Huijie Bian,Ying Liu,Xiaolei Zhu,Yun Xu
标识
DOI:10.1038/s41386-022-01435-w
摘要
Alzheimer's disease (AD) is the most common neurodegenerative disease and has an insidious onset. Exploring the characteristics and mechanism of the early symptoms of AD plays a critical role in the early diagnosis and intervention of AD. Here we found that depressive-like behavior and short-term spatial memory dysfunction appeared in APPswe/PS1dE9 mice (AD mice) as early as 9-11 weeks of age. Electrophysiological analysis revealed excitatory/inhibitory (E/I) imbalance in the prefrontal cortex (PFC). This E/I imbalance was induced by significant reduction in the number and activity of parvalbumin interneurons (PV+ INs) in this region. Furthermore, optogenetic and chemogenetic activation of residual PV+ INs effectively ameliorated depressive-like behavior and rescued short-term spatial memory in AD mice. These results suggest the PFC is selectively vulnerable in the early stage of AD and prefrontal PV+ INs deficits play a key role in the occurrence and development of early symptoms of AD.
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