海马CA3区θ~γ神经振荡模拟刺激对大鼠空间认知能力的影响

Effect ofθ–γneural oscillation stimulation in hippocampal CA3 area on spatial cognition ability in rats

目的:探讨海马CA3区θ~γ神经振荡模拟交替刺激对大鼠空间认知能力的影响及其机制。方法:依据迷宫电击回避实验结果将实验大鼠分为快回避反应组和普通回避反应组;利用在体脑深部刺激方法,模拟快回避反应组内生θ~γ神经振荡刺激普通回避反应大鼠海马CA3区,即为模拟刺激组。利用Y迷宫电击回避实验检测模拟刺激对大鼠空间认知能力的影响;利用小波包提取方法分析模拟刺激后大鼠海马CA3区θ~γ神经振荡相位-幅度耦合情况;利用蛋白质印迹法检测大鼠海马组织N-甲基-D-天冬氨酸受体2B(NR2B)亚型、突触后致密区95(PSD-95)的表达。结果:与普通回避反应组比较,模拟刺激组电击回避训练达标所需时间、达标所需测试次数、正确反应时间、错误反应次数均明显减少,正确反应率明显提高(均P<0.01);同时,模拟刺激组海马CA3区θ~γ神经振荡多个频段(3~5 Hz与30~34、38~42、44~48 Hz;5~7 Hz与42~46、44~48、54~58 Hz)耦合度明显高于普通回避反应组(均P<0.05);另外,模拟刺激组海马NR2B亚型及PSD-95表达量显著增加(均P<0.05)。结论:大鼠海马内生θ~γ神经振荡模拟交替刺激明显提高了普通回避反应大鼠空间认知能力,而这种空间认知能力的提高可能是由PSD-95调控的NR2B亚型介导的突触可塑性增强引起。

Objective: To investigate the effects ofθ–γneural oscillation stimulation in hippocampal CA3 area on spatial cognition ability in rats.Methods: According to the results of Y maze shock avoidance training, the rats were divided into fast avoidance response group and general avoidance response group. Using endogenousθ–γneural oscillations from the fast avoidance response rats to perform deep brain stimulationin vivo to the left and right hippocampal CA3 region of rats with general avoidance response, then the spatial cognition was tested by Y maze shock avoidance training. The variation ofθoscillation and low-γneural oscillation phase-amplitude coupling(PAC) in CA3 area was analyzed by wavelet packet extraction technique. Western blotting was used to detect the expression ofN-methyl-D-aspartate receptor 2 B subunit(NR2 B) and postsynaptic density(PSD)-95 in hippocampal tissues of rats to explore its molecular mechanism.Results:Compared with the general avoidance response rats, the days to reach the standard, the training number, the correct response time and the error reaction number in simulated stimulus avoidance response rats were significantly reduced, but the correct response rate was significantly increased(allP<0.01);theθ–γneural oscillations PAC in the hippocampal CA3 region in the simulated stimulus avoidance response rats(3–5 Hz and30–34, 38–42, 44–48 Hz;5–7 Hz and 42–46, 44–48, 54–58 Hz) were significantly higher than that in the general avoidance response rats(allP<0.05). Meanwhile, the protein expressions of NR2 B and PSD-95 in hippocampal tissues were significantly increased(bothP<0.05) in simulated stimulus avoidance response rats.Conclusion: The spatial cognition of normal avoidance response rats can be significantly improved by endogenousθ–γneural oscillation stimulation to hippocampal CA3 region, which may be caused by the enhancement of synaptic plasticity mediated by NR2 B and PSD-95.