Altered Hippocampal-Prefrontal Dynamics Following Medial Prefrontal Stroke in Mouse

Altered Hippocampal-Prefrontal Dynamics Following Medial Prefrontal Stroke in Mouse
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DOI:
10.1007/s12017-019-08557-3
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发表时间:
2019-12-01
影响因子:
3.5
通讯作者:
Clarkson, Andrew N.
Clarkson, Andrew N.
中科院分区:
医学3区
文献类型:
--
作者:
Hillman, Kristin L.;Wall, Hannah J.;Clarkson, Andrew N.

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额叶梗塞可产生认知障碍,影响个体在日常生活中的功能。然而,赤字的确切类型及其潜在机制尚未得到很好的理解。在这里,我们使用C57 BL/6 J小鼠的前额光血栓性中风模型来观察中风后6周内发生的特定认知变化。行为实验与体内电生理学配对,以评估前额叶皮层(PFC)和海马(HPC)之间的振荡通信的变化是否反映了任何观察到的行为变化。我们发现,中风组小鼠在空间工作记忆任务(物体位置识别和Y迷宫)中表现出延迟发作的损伤,并且这与任务期间PFC-HPC θ波段相干性(5-12 Hz)降低相关。在开放视野中,与对照组相比,中风组小鼠表现出活动过度,中风动物在PFC和HPC中也表现出显著更高的β带活动(13-30 Hz)。综上所述,我们的研究结果表明,在PFC的梗死导致PFC-HPC振荡通信的变化,在θ和β带,分别与空间记忆和开放领域的任务的性能改变。特别令人感兴趣的是,中风后PFC β带功率的早期旷场变化与后期空间记忆障碍相关,突出显示这是检测空间记忆障碍何时可能发生的潜在生物标志物。
Frontal infarcts can produce cognitive impairments that affect an individual's ability to function in everyday life. However, the precise types of deficits, and their underlying mechanisms, are not well-understood. Here we used a prefrontal photothrombotic stroke model in C57BL/6J mice to characterise specific cognitive changes that occur in the 6 weeks post-stroke. Behavioural experiments were paired with in vivo electrophysiology to assess whether changes in oscillatory communication between the prefrontal cortex (PFC) and the hippocampus (HPC) mirrored any observed behavioural changes. We found that mice in the stroke group exhibited a delayed onset impairment in tasks of spatial working memory (object location recognition and Y-maze) and that this correlated with reduced PFC-HPC theta band coherence (5-12 Hz) during the task. In the open field, mice in the stroke group exhibited hyperactivity as compared to controls, and stroke animals also exhibited significantly higher beta band activity (13-30 Hz) in the PFC and the HPC. Taken together our results suggest that infarcts in the PFC result in PFC-HPC oscillatory communication changes in the theta and beta bands, correlating with altered performance in spatial memory and open field tasks respectively. Of particular interest, early open field changes in PFC beta band power post-stroke correlated to later-stage spatial memory impairments, highlighting this as a potential biomarker for detecting when spatial memory impairments are likely to occur.