40Hz光闪烁刺激对大鼠空间工作记忆影响及其神经机制研究

Study on effects of 40 Hz light flicker stimulation on spatial working memory in rats and its neural mechanism

阿尔茨海默症(AD)是一种以认知障碍为特征的神经退行性疾病,其主要临床表现是空间工作记忆(SWM)障碍,严重影响患者身心健康,而现有药物疗法存在治愈率低等问题,因此非药物物理疗法逐渐受到人们广泛关注。近年来,一种通过40 Hz光闪烁刺激(40 Hz-LFS)改善AD模型动物SWM功能的新方案取得初步进展,然而具体神经机制尚不清楚。因此,本研究将基于交叉频率耦合(CFC)探究40 Hz-LFS调控SWM功能的潜在神经机制。本文以10只成年维斯塔尔(Wistar)大鼠为研究对象,首先应用20、40、60 Hz的频率进行光闪烁刺激(LFS)实时作用,分析不同频率LFS对海马体(HPC)和内侧前额叶皮层(mPFC)神经振荡的夹带效应。结果显示,40 Hz-LFS能够形成夹带效应,调控低频γ(lγ)节律振荡的活动强度;随后将大鼠分为实验组和对照组,每组5只,进行40 Hz-LFS长期作用(7 d),并通过T迷宫任务检测其SWM功能,应用相位幅值耦合(PAC)分析HPC与mPFC间(HPC-mPFC)回路的CFC变化。结果表明,实验组的行为学表现得到提升,θ节律和lγ(θ-lγ)的PAC增强,差异具有统计学意义。本文研究结果提示,长期40 Hz-LFS能够有效改善大鼠的SWM功能,其原因可能是促进了相关神经回路中振荡的跨节律信息交流。期望通过本文研究,可为今后进一步研究40 Hz-LFS改善认知功能的机制及促进其临床应用奠定基础。

Alzheimer’s disease(AD)is a neurodegenerative disease characterized by cognitive impairment,with the predominant clinical diagnosis of spatial working memory(SWM)deficiency,which seriously affects the physical and mental health of patients.However,the current pharmacological therapies have unsatisfactory cure rates and other problems,so non-pharmacological physical therapies have gradually received widespread attention.Recently,a novel treatment using 40 Hz light flicker stimulation(40 Hz-LFS)to rescue the cognitive function of model animals with AD has made initial progress,but the neurophysiological mechanism remains unclear.Therefore,this paper will explore the potential neural mechanisms underlying the modulation of SWM by 40 Hz-LFS based on cross-frequency coupling(CFC).Ten adult Wistar rats were first subjected to acute LFS at frequencies of 20,40,and 60 Hz.The entrainment effect of LFS with different frequency on neural oscillations in the hippocampus(HPC)and medial prefrontal cortex(mPFC)was analyzed.The results showed that acute 40 Hz-LFS was able to develop strong entrainment and significantly modulate the oscillation power of the low-frequency gamma(lγ)rhythms.The rats were then randomly divided into experimental and control groups of 5 rats each for a long-term 40 Hz-LFS(7 d).Their SWM function was assessed by a T-maze task,and the CFC changes in the HPC-mPFC circuit were analyzed by phase-amplitude coupling(PAC).The results showed that the behavioral performance of the experimental group was improved and the PAC ofθ-lγrhythm was enhanced,and the difference was statistically significant.The results of this paper suggested that the long-term 40 Hz-LFS effectively improved SWM function in rats,which may be attributed to its enhanced communication of different rhythmic oscillations in the relevant neural circuits.It is expected that the study in this paper will build a foundation for further research on the mechanism of 40 Hz-LFS to improve cognitive function and promote its clinical application in the future.