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浙江大学学报(医学版)  2021, Vol. 50 Issue (6): 762-769    DOI: 10.3724/zdxbyxb-2021-0165
原著     
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
李敏1,*,朱再满1,叶政2,王惠1,刘克宇3
1.皖南医学院生理学教研室,安徽 芜湖 241002
2.皖南医学院临床医学院,安徽 芜湖 241002
3.皖南医学院研究生学院,安徽 芜湖 241002
Effect of θ–γ neural oscillation stimulation in hippocampal CA3 area on spatial cognition ability in rats
LI Min1,*,ZHU Zaiman1,YE Zheng2,WANG Hui1,LIU Keyu3
1. Department of Physiology, Wannan Medical College, Wuhu 241002, Anhui Province, China;
2. Clinical Medical College, Wannan Medical College, Wuhu 241002, Anhui Province, China;
3. Graduate School, Wannan Medical College, Wuhu 241002, Anhui Province, China
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摘要:

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。

关键词: 海马神经振荡脑深部刺激Y迷宫电击回避实验N-甲基-D-天冬氨酸受体2B亚型突触后致密区95大鼠    
Abstract:

Objective:To investigate the effects of θ–γ neural 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 endogenous θ–γ neural oscillations from the fast avoidance response rats to perform deep brain stimulation in 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 of θ oscillation and low-γ neural oscillation phase-amplitude coupling (PAC) in CA3 area was analyzed by wavelet packet extraction technique. Western blotting was used to detect the expression of N-methyl-D-aspartate receptor 2B subunit (NR2B) 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 (all P<0.01); the θ–γ neural oscillations PAC in the hippocampal CA3 region in the simulated stimulus avoidance response rats (3–5?Hz and 30–34, 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 NR2B 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 endogenous θ–γ neural oscillation stimulation to hippocampal CA3 region, which may be caused by the enhancement of synaptic plasticity mediated by NR2B and PSD-95.

Key words: Hippocampus    Neural oscillation    Deep brain stimulation    Y maze shock avoidance training    N-methyl-D-aspartate receptor 2B subunit    Postsynaptic density-95    Rats
收稿日期: 2021-06-15 出版日期: 2022-03-22
CLC:  R338.2  
基金资助: 安徽省高等学校自然科学研究项目(KJ2020A0606,KJ2019A0407,KJ2018A0268);2017年高校优秀青年人才支持计划(gxyq2017038);皖南医学院重点项目科研基金(WK201801,WK201515)
通讯作者: 李敏   
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引用本文:

李敏,朱再满,叶政,王惠,刘克宇. 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[J]. 浙江大学学报(医学版), 2021, 50(6): 762-769.

LI Min,ZHU Zaiman,YE Zheng,WANG Hui,LIU Keyu. Effect of θ–γ neural oscillation stimulation in hippocampal CA3 area on spatial cognition ability in rats. J Zhejiang Univ (Med Sci), 2021, 50(6): 762-769.

链接本文:

https://www.zjujournals.com/med/CN/10.3724/zdxbyxb-2021-0165        https://www.zjujournals.com/med/CN/Y2021/V50/I6/762

组别

n

电击回避训练达标所需时间

达标所需测试次数

正确反应率(%)

正确反应时间(s)

主动回避率(%)

错误反应次数

普通回避反应组

10

3.53±0.75

74.5±15.40

0.62±0.05

6.46±2.54

0.05±0.05

24.83±9.01

快回避反应组

10

0.80±0.21*

17.03±5.99*

0.86±0.11*

5.11±3.31*

0.05±0.11

3.36±2.75*

模拟刺激组

10

1.00±0.00*

20.00±0.00*

0.77±0.07*

2.48±0.71*

0.08±0.07

5.00±3.41*

表 1  三组Y迷宫电击回避实验观察指标比较
图 1  模拟刺激前后大鼠海马CA3区θ波与γ波神经振荡耦合分析A:普通回避反应组;B:模拟刺激组.

组别

n

3~5?Hz θ波

5~7?Hz θ波

30~34?Hz γ波

38~42?Hz γ波

44~48?Hz γ波

42~46?Hz γ波

44~48?Hz γ波

54~58?Hz γ波

普通回避反应组

10

4.25±0.49

7.20±0.84

11.22±2.26

6.80±0.74

7.42±0.68

6.33±0.63

模拟刺激组

10

6.63±0.67*

12.53±1.23*

18.59±2.63*

12.03±1.07*

11.66±1.11*

9.99±0.97*

表 2  模拟刺激前后大鼠海马CA3区θ波与γ波神经振荡耦合调制指数比较
图 2  三组海马NR2B亚型和PSD-95蛋白表达电泳图NR2B:-甲基--天冬氨酸受体2B亚型;PSD:突触后致密区.

组别

n

NR2B

PSD-95

普通回避反应组

10

0.54±0.02

0.23±0.03

快回避反应组

10

0.81±0.07*

0.58±0.05*

模拟刺激组

10

0.96±0.07*

1.00±0.09*#

表 3  三组海马NR2B亚型和PSD-95蛋白表达量比较
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