海马<strong>CA3</strong>区θ~γ神经振荡模拟刺激对大鼠空间认知能力的影响

doi:10.3724/zdxbyxb-2021-0165

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 Min^1,*,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 或 https://www.zjujournals.com/med/CN/Y2021/V50/I6/762

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.

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.

表 3 三组海马NR2B亚型和PSD-95蛋白表达量比较

1	CHAIEBL, LESZCZYNSKIM, AXMACHERN, et al.Theta-gamma phase-phase coupling during working memory maintenance in the human hippocampus[J]Cogn Neurosci, 2015, 6( 4): 149-157. doi: 10.1080/17588928.2015.1058254
2	SAUSENGP, PEYLOC, BIELA L, et al.Does cross‐frequency phase coupling of oscillatory brain activity contribute to a better understanding of visual working memory?[J]Br J Psychol, 2019, 110( 2): 245-255. doi: 10.1111/bjop.12340
3	VIVEKANANDAU, BUSHD, BISBYJ A, et al.Theta power and theta‐gamma coupling support long‐term spatial memory retrieval[J]Hippocampus, 2021, 31( 2): 213-220. doi: 10.1002/hipo.23284
4	GOODMANM S, KUMARS, ZOMORRODIR, et al.Theta-gamma coupling and working memory in Alzheimer’s dementia and mild cognitive impairment[J]Front Aging Neurosci, 2018, 101. doi: 10.3389/fnagi.2018.00101
5	TIANY, ZHOUH, ZHANGH, et al.Research on differential brain networks before and after WM training under different frequency band oscillations[J]Neural Plast, 2021, 6628021. doi: 10.1155/2021/6628021
6	KIROVR, WEISSC, SIEBNERH R, et al.Slow oscillation electrical brain stimulation during waking promotes EEG theta activity and memory encoding[J]Proc Natl Acad Sci U S A, 2009, 106( 36): 15460-15465. doi: 10.1073/pnas.0904438106
7	HANSLMAYRS, AXMACHERN, INMANC S. Modulating human memory via entrainment of brain oscillations[J]Trends Neuroscis, 2019, 42( 7): 485-499. doi: 10.1016/j.tins.2019.04.004
8	PADILLA-COREANON, CANETTAS, MIKOFSKYR M, et al.Hippocampal-prefrontal theta transmission regulates avoidance behavior[J]Neuron, 2019, 104( 3): 601-610.e4. doi: 10.1016/j.neuron.2019.08.006
9	汪炜炜, 王丹丹, 王丹, 等. 电击回避训练前后快回避反应大鼠海马CA3区神经振荡的变化[J]. 生理学报, 2015, 67(5): 487-496 WANG Weiwei, WANG Dandan, WANG Dan, et al. Alteration of neural oscillations in hippocampal CA3 area in the fast avoidance response rat before and after electric shock avoidance training[J]. Acta Physiologica Sinica, 2015, 67(5): 487-496. (in Chinese)
10	王丹丹, 王羽, 汪镜静, 等. 高脂饲养青春期大鼠电击回避反应和海马CA3区场电位的改变[J]. 中国应用生理学杂志, 2016, 32(6): 545-549 WANG Dandan, WANG Yu, WANG Jinjing, et al. The changes of electric shock avoidance response and local field potentials on hippocampal CA3 region of the adolescent rats with high fat feeding[J]. Chinese Journal of Applied Physiology, 2016, 32(6): 545-549. (in Chinese)
11	李敏, 叶政, 朱再满, 等. 大鼠海马CA3区θ~γ神经振荡与空间认知能力相关性研究[J]. 生理学报, 2021,73(5): 855-862 LI Min, YE Zheng, ZHU Zaiman, et al. Correlation between theta–gamma neural oscillations in hippocampal CA3 area and the spatial identifying and cognitive ability in rats[J]. Acta Physiologica Sinica, 2021,73(5): 855-862. (in Chinese)
12	AXMACHERN, HENSELERM M, JENSENO, et al.Cross-frequency coupling supports multi-item working memory in the human hippocampus[J]Proc Natl Acad Sci U S A, 2010, 107( 7): 3228-3233. doi: 10.1073/pnas.0911531107
13	THUTG, SCHYNSP G, GROSSJ. Entrainment of perceptually relevant brain oscillations by non-invasive rhythmic stimulation of the human brain[J]Front Psychol, 2011, 170. doi: 10.3389/fpsyg.2011.00170
14	HAEGENSS, ZION GOLUMBICE. Rhythmic facilitation of sensory processing: a critical review[J]Neurosci Biobehaval Rev, 2018, 150-165. doi: 10.1016/j.neubiorev.2017.12.002
15	CALDERONED J, LAKATOSP, BUTLERP D, et al.Entrainment of neural oscillations as a modifiable substrate of attention[J]Trends Cogn Sci, 2014, 18( 6): 300-309. doi: 10.1016/j.tics.2014.02.005
16	FOSTERT C. Dissecting the age-related decline on spatial learning and memory tasks in rodent models: N-methyl-D-aspartate receptors and voltage-dependent Ca2+ channels in senescent synaptic plasticity[J]Prog Neurobiol, 2012, 96( 3): 283-303. doi: 10.1016/j.pneurobio.2012.01.007
17	MISHIBAT, TANAKAM, MITAN, et al.Cdk5/p35 functions as a crucial regulator of spatial learning and memory[J]Mol Brain, 2014, 7( 1): 82. doi: 10.1186/s13041-014-0082-x
18	王庭槐. 生理学[M]. 北京: 人民卫生出版社, 2018: 351 WANG Tinghuai. Physiology[M]. Beijing: People’s Medical Publishing House, 2018: 351. (in Chinese)
19	BAEZM V, CERCATOM C, JERUSALINSKYD A. NMDA receptor subunits change after synaptic plasticity induction and learning and memory acquisition[J]Neural Plast, 2018, 5093048. doi: 10.1155/2018/5093048
20	WANGX P, YEP, LVJ, et al.Expression changes of NMDA and AMPA receptor subunits in the hippocampus in rats with diabetes induced by streptozotocin coupled with memory impairment[J]Neurochem Res, 2019, 44( 4): 978-993. doi: 10.1007/s11064-019-02733-4
21	李明超, 叶云, 刘远, 等. 离子型谷氨酸受体在长时程增强产生机制中的研究进展[J].中国实用神经疾病杂志, 2018, 16(22): 1741-1745 LI Mingchao, YE Yun, LIU Yuan, et al. The research progress of ionic glutamate receptor in the mechanism of long-time potentiation[J].Chinese Journal of Practical Nervours Diseases, 2018, 16(22): 1741-1745. (in Chinese)
22	WANGH, PENGR, ZHAOL, et al.The relationship between NMDA receptors and microwave-induced learning and memory impairment: a long-term observation on wistar rats[J]Int J Radiat Biol, 2015, 91( 3): 262-269. doi: 10.3109/09553002.2014.988893
23	SHIRAISHIY, MIZUTANIA, MIKOSHIBAK, et al.Coincidence in dendritic clustering and synaptic targeting of homer proteins and NMDA receptor complex proteins NR2B and PSD95 during development of cultured hippocampal neurons[J]Mol Cell Neurosci, 2003, 22( 2): 188-201. doi: 10.1016/s1044-7431(03)00037-x
24	DOREK, CARRICOZ, ALFONSOS, et al.PSD-95 protects synapses from β-amyloid[J]Cell Rep, 2021, 35( 9): 109194. doi: 10.1016/j.celrep.2021.109194
25	TAFTC E, TURRIGIANOG G. PSD-95 promotes the stabilization of young synaptic contacts[J]Phil Trans R Soc B, 2014, 369( 1633): 20130134. doi: 10.1098/rstb.2013.0134
26	QINL, MARRSG S, MCKIMR, et al.Hippocampal mossy fibers induce assembly and clustering of PSD95-containing postsynaptic densities independent of glutamate receptor activation[J]J Comp Neurol, 2001, 440( 3): 284-298. doi: 10.1002/cne.1386
27	MAJ, WANGJ, LVC, et al.The role of hippocampal structural synaptic plasticity in repetitive transcranial magnetic stimulation to improve cognitive function in male SAMP8 mice[J]Cell Physiol Biochem, 2017, 41( 1): 137-144. doi: 10.1159/000455982

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