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J Zhejiang Univ (Med Sci)  2021, Vol. 50 Issue (6): 762-769    DOI: 10.3724/zdxbyxb-2021-0165
    
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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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 wordsHippocampus      Neural oscillation      Deep brain stimulation      Y maze shock avoidance training      N-methyl-D-aspartate receptor 2B subunit      Postsynaptic density-95      Rats     
Received: 15 June 2021      Published: 22 March 2022
CLC:  R338.2  
Corresponding Authors: LI Min   
Cite this article:

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.

URL:

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


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

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 

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*

Table 1 Comparison of observation indexes of Y maze electric shock avoidance training among three groups
Figure 1 Analysis of θ–γ phase-amplitude coupling in CA3 area before and after θ–γ neural oscillations stimulation

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*

Table 2 Modulation indexes of θ rhythm and γ rhythm before and after θ–γ neural oscillations stimulation
Figure 2 The protein expressions of NR2B subunit and PSD-95 in hippocampal tissue

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*#

Table 3 Comparison of NR2B subunit and PSD-95 protein expression in the hippocampal tissue of rats
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