生理及病理状态下大鼠海马θ节律振荡与空间学习记忆的相关性研究

The correlatation study between hippocampal cholinergic θ rhythm and spatial memory in rats under physiological and pathological conditions

关键词:  海马θ节律振荡  空间学习记忆  淀粉样β蛋白  阿尔茨海默病

Key words:  hippocampal θ rhythm  spatial learning and memory  amyloid β protein  Alzheimer's disease

摘要:

[目的] 探讨生理及病理状态下，麻醉大鼠感觉刺激诱导的海马胆碱能θ（theta）节律振荡与其空间学习记忆行为的相关性，分析海马胆碱能θ节律振荡在空间学习记忆中的作用，同时为其用作评估大鼠空间学习记忆能力的电生理指标提供实验依据。[方法] 使用同一批大鼠进行Morris水迷宫测试和在体海马胆碱能θ节律振荡的自身相关比较实验。实验主要指标包括：大鼠在水迷宫定位航行实验中的逃避潜伏期、空间探索实验中在目标象限的游泳时间百分比、可见平台实验中的逃避潜伏期、游泳速度以及由夹尾刺激诱导θ节律振荡的功率峰值（P_peak）及其对应的频率值（F_peak）。[结果] 双侧海马注射全长的淀粉样β蛋白（Aβ）明显的损害了大鼠在水迷宫中的学习（P<0.05）及记忆（P<0.01）能力，同时压抑了感觉刺激诱导的胆碱能θ节律振荡的P_peak（P<0.01）。正常对照组（生理组）及Aβ海马注射组（病理组）大鼠胆碱能θ节律振荡的P_peak均与定位航行实验中逃避潜伏期呈明显负相关（正常对照组：r=-0.803，P<0.05；Aβ海马注射组：r=-0.764，P<0.05），且与空间探索实验中目标象限游泳实验百分比呈明显正相关（正常对照组：r=0.762，P<0.05；Aβ海马注射组：r=0.771，P<0.05）。将两组数据合并后，胆碱能θ节律振荡P_peak与逃避潜伏期和目标象限游泳时间百分比的相关性更高，分别为：r=-0.896（P<0.01）和r=0.888（P<0.01）。[结论] 感觉刺激诱导的大鼠海马胆碱能θ节律振荡的功率值与其空间学习记忆能力存在良好的相关性，提示海马胆碱能θ节律振荡作为一种神经网络同步化电活动可能参与学习记忆行为，而其功率大小可用于间接评估实验动物的空间学习记忆能力，为中医治疗阿尔茨海默病（AD）的实验研究提供动物模型的基础。

Abstract:

[Objective] To investigate the correlation between hippocampal cholinergic θ rhythm and spatial learning and memory under physiological and pathological conditions, further clarify the association between the cognitive deficits and the hippocampal θ synchronization disorder. This article also wants to provide the experimental evidence evaluating the ability of spatial learning and memory in rodents by recording the hippocampal cholinergic θ rhythm. [Methods] Tai-pinch induced hippocampal cholinergic θ rhythm was recorded after Morris water maze test on the same SD rats. Main indicators including: the latencies in the hidden platform test, the percentage of swimming time in target quadrant in the probe trial test, the swimming speed and the latencies in the visible platform test, the peak power (P_peak) and average peak frequency (F_peak) of θ rhythm. [Results] Bilateral intrahippocampal injection of full length amyloid β peptide (Aβ-42) significantly impaired spatial learning (P<0.05) and memory (P<0.05) of rats in Morris water maze test and reduced the P_peak of hippocampal cholinergic θ rhythm (P<0.05). In control group, there was a significant negative correlation between the P_peak of hippocampal cholinergic θ rhythm and the escape latency (r=-0.803,P<0.05) and a significant positive correlation between the P_peak of hippocampal cholinergic θ rhythm and the percentage of swimming time in target quadrant (r=0.762,P<0.05). Similar correlations were found with a correlation coefficient of r=-0.764 (P<0.05) and r=0.771 (P<0.05) respectively in Aβ_1-42 injection group. Taken these as a whole,the P_peak of hippocampal cholinergic θ rhythm was more correlated with escape latency (r=-0.896, P<0.01) and swimming time percentage (r=0.888, P<0.01). [Conclusions] There is strong correlation between the hippocampal cholinergic θ rhythm and the spatial learning and memory ability in rats, suggesting the somatosensory stimulation induced hippocampal cholinergic θ rhythm may be involved in the spatial learning and memory consolidation in rats. The power of hippocampal cholinergic θ rhythm may be an indicator to assess the ability of spatial learning and memory in rats.