5-羟色胺在大鼠海马CA1、CA2和CA3的表达
|
摘要
目的：大鼠海马属于脑的边缘系统,包括CA1、CA2和CA3。在结构上无明显分界标志,功能上可视为一个整体。5-羟色胺(5-HT),一种在中枢神经系统广泛分布的神经递质,主要参与情感、睡眠、疼痛、学习记忆等复杂生理功能的调节。为了解5-羟色胺在海马中的分布特点,本实验采用5-HT特异性抗体的方法,利用免疫组织化学技术,观察海马CA1、CA2和CA3中三个区域5-HT神经元及神经纤维终末的表达,为进一步研究5-HT在海马学习、记忆的作用机制,提供形态学依据。
方法：1、实验动物和主要试剂：成年雄性SD大鼠8只(由大连医科大学实验动物中心提供)、山羊超敏二步法免疫组化检测试剂、浓缩型DAB(购自北京中杉金桥)。2、灌注固定：把大鼠经10%水合氯醛进行腹腔麻醉。仰卧固定,用剪刀打开胸腔,将穿刺针经左心室插入升主动脉,剪开右心耳,先用150ml生理盐水快速冲洗后,给予4%多聚甲醛磷酸缓冲液300ml灌注,持续灌注4小时后断头开颅取脑,放入相同固定液中4℃过夜。在振动切片机连续冠状切片,片厚30um,选取具有海马的切片,置入0.01mol/L的PBS(PH值7.4)溶液中备用。3、免疫组织化学法：采用二步法进行免疫组织化学染色。4、统计学分析：在正置荧光显微镜图像分析仪观察拍摄,核团定位参照George Raxinos,Charles Watsonbian编著的The Rat Brain in stereotaxic coordinates(大鼠脑立体定位图谱,第三版)。在低倍镜下观察海马和5-HT阳性神经元在海马中CA1、CA2和CA3区的表达。在高倍镜下观察5-HT阳性神经纤维终末。所得数据采用SPSS16.5软件分析。
结果：在低倍光镜下观察：1、大鼠海马内5-HT免疫反应产物为棕黄色(图1 a),可见大量的5-HT能阳性神经元和树突。阳性产物位于胞浆中,细胞核透明,未见明显染色(图2a,3a,4a)2、免疫反应阳性产物在海马锥体层细胞中分布最多,密集呈带。3、在20×10倍光镜下计数,CA2区免疫反应阳性神经元数最多,其次是CA1区,CA3区最少。4、CA3的细胞比其它区域略小,染色比CA1区弱。在高倍镜下：1、在海马CA1、CA2和CA3中呈阳性反应的神经元胞体为圆形或卵圆形。2、海马内可见免疫反应阳性、呈串珠状的5-HT能神经纤维终末(图2b,3b,4b)。免疫反应对照切片为阴性(4×10),未见CA1、CA2和CA3区有5.HT免疫反应阳性神经元及神经纤维终末表达。统计学结果：CA1、CA2和CA3区阳性神经元平均数士标准差分别是5.60±1.075,5.70±1.252,3.50±1.269。经统计学分析CA1、CA2与CA3区阳性神经元数之间比较有统计学差异,CA1>CA3, CA2>CA3 (P<0.01)。
结论：1、大鼠海马内有5-HT能神经元和神经纤维终末表达。2、5-HT免疫阳性产物在CA1、CA2与CA3区表达强度有差异,其阳性神经元数CA1>CA3, CA2>CA3。
Objective:Hippocampus of rats blongs to of limbic system brain, including CA1, CA2 and CA3. It is no significant boundary in the structures, and function can be considered as a whole.5-hydroxytryptamine (5-HT), a kind of wide neurotransmitter in the central nervous system have mainly involved in emotion, sleep, pain, learning and memory and other complex regulation of physiological functions。In order to understand the 5-HT in the hippocampus of the distribution, the experiments was held, observed in hippocampus CA1, CA2 and CA3 three regional the positive neurons and 5-HT positive nerve fiber terminals in the expression, for further study of 5-HT in the hippocampus learning and memory mechanism, providing morphological evidence.
Method:1、The experimental animals and main reagents:8 adult male SD rats (from the Experimental Animal Center of Dalian Medical University).Polink-2 plus polymer HRP detection system for goat primary antibody.and 3,3,-Diaminobenzidine tetrahydrochloride substrate kit, Immunohistochemistry kit (from ZSGB-BIO) 2、perfusion and fixation:the rats were taken firstly based anesthesi in the cylinder by Ether, and then was carried out intraperitoneal anesthesia by chloral hydrate(10%), Opened the chest with scissors, with the puncture needle from the left ventricle to ascending aorta, cut the right atrial appendage, first washed with 150ml NaCL(0.9%) quick and perfusated paraformaldehyde(4%) in PBS 300ml, was cut cranial brain and placed in the PBS overnight at 4℃. It was cut into slice serial coronal sections in the vibrating slicer, it be selected the slice with the hippocampus, placed in 0.01mol/L of PBS(PH7.4) solution. 3、immunohistochemistry:The experiments was used to be two-step immunohistochemical staining. 4、statistical analysis:It was observed In Nikon (ECLIPSE80i) by fluorescence microscope image analyzer and the image analysis software with their own analysis of the data. Localization of nuclei of light depend on The Rat Brain in stereotaxic coordinates (third edition).It was observed that the hippocampal area and the 5-HT-positive nerve cells at the low microscope, It was counted 5-HT-positive neurons in the hippocampus CA1, CA2 and CA3 areas in the 10×20 light microscope.It was Observed that 5-HT positive nerve fiber terminals at high he low microscope.The data analysises with the soft SPSS16.5.
Result:At low light microscope:1.The 5-HT immunoreactive product was brown in the hippocampus,a large number of 5-HT positive neurons can be discoveried, positive products were located around the nucleus, the nuclear transparency has not significant stained.2.Immunoreactive cells was band in the hippocampal pyramidal layer of the distribution 3.Counting in 20×10 light microscope immunoreactive cell bodies of CA2 area is the most, followed in the CA1 area, CA3 area are least. there are significant differences by statistical analysis among the CA1, CA2 and CA3 area the number of positive neurons, CA1>CA3, CA2>CA3 (P<0.01).4.The cells of CA3 area is larger than other regions, but weaker staining than the CA1 area. At the high microscope: 1.It shows that more immune 5-HT-positive nerve fibers and terminal 5-HT nerve fibers were beaded terminals (Figure 2b,3b, 4b).2.The positive neurons were round or oval.Otherwise,at the light microscope,the control sections have no expression of anti-5-HT immunoreactive cell body and anti-5-HT immunoreactive nerve fiber terminals in CA1, CA2 and CA3 areas.Its mean values are 5.60±1.075, 5.70±1.252,3.50±1.269.
Conclusion:1.There exist 5-HT nerve fiber terminals and cell bodies in the CA1,CA2 and CA3 of hippocampus.2.The expression of 5-HT immunoreactive products in CA1, CA2 and CA3 areas is uneven, the number of positive neurons is CA1>CA3,CA2>CA3.We conclude that 5-HT neurons may play a role as interneurons in hippocampus
方法：1、实验动物和主要试剂：成年雄性SD大鼠8只(由大连医科大学实验动物中心提供)、山羊超敏二步法免疫组化检测试剂、浓缩型DAB(购自北京中杉金桥)。2、灌注固定：把大鼠经10%水合氯醛进行腹腔麻醉。仰卧固定,用剪刀打开胸腔,将穿刺针经左心室插入升主动脉,剪开右心耳,先用150ml生理盐水快速冲洗后,给予4%多聚甲醛磷酸缓冲液300ml灌注,持续灌注4小时后断头开颅取脑,放入相同固定液中4℃过夜。在振动切片机连续冠状切片,片厚30um,选取具有海马的切片,置入0.01mol/L的PBS(PH值7.4)溶液中备用。3、免疫组织化学法：采用二步法进行免疫组织化学染色。4、统计学分析：在正置荧光显微镜图像分析仪观察拍摄,核团定位参照George Raxinos,Charles Watsonbian编著的The Rat Brain in stereotaxic coordinates(大鼠脑立体定位图谱,第三版)。在低倍镜下观察海马和5-HT阳性神经元在海马中CA1、CA2和CA3区的表达。在高倍镜下观察5-HT阳性神经纤维终末。所得数据采用SPSS16.5软件分析。
结果：在低倍光镜下观察：1、大鼠海马内5-HT免疫反应产物为棕黄色(图1 a),可见大量的5-HT能阳性神经元和树突。阳性产物位于胞浆中,细胞核透明,未见明显染色(图2a,3a,4a)2、免疫反应阳性产物在海马锥体层细胞中分布最多,密集呈带。3、在20×10倍光镜下计数,CA2区免疫反应阳性神经元数最多,其次是CA1区,CA3区最少。4、CA3的细胞比其它区域略小,染色比CA1区弱。在高倍镜下：1、在海马CA1、CA2和CA3中呈阳性反应的神经元胞体为圆形或卵圆形。2、海马内可见免疫反应阳性、呈串珠状的5-HT能神经纤维终末(图2b,3b,4b)。免疫反应对照切片为阴性(4×10),未见CA1、CA2和CA3区有5.HT免疫反应阳性神经元及神经纤维终末表达。统计学结果：CA1、CA2和CA3区阳性神经元平均数士标准差分别是5.60±1.075,5.70±1.252,3.50±1.269。经统计学分析CA1、CA2与CA3区阳性神经元数之间比较有统计学差异,CA1>CA3, CA2>CA3 (P<0.01)。
结论：1、大鼠海马内有5-HT能神经元和神经纤维终末表达。2、5-HT免疫阳性产物在CA1、CA2与CA3区表达强度有差异,其阳性神经元数CA1>CA3, CA2>CA3。
Objective:Hippocampus of rats blongs to of limbic system brain, including CA1, CA2 and CA3. It is no significant boundary in the structures, and function can be considered as a whole.5-hydroxytryptamine (5-HT), a kind of wide neurotransmitter in the central nervous system have mainly involved in emotion, sleep, pain, learning and memory and other complex regulation of physiological functions。In order to understand the 5-HT in the hippocampus of the distribution, the experiments was held, observed in hippocampus CA1, CA2 and CA3 three regional the positive neurons and 5-HT positive nerve fiber terminals in the expression, for further study of 5-HT in the hippocampus learning and memory mechanism, providing morphological evidence.
Method:1、The experimental animals and main reagents:8 adult male SD rats (from the Experimental Animal Center of Dalian Medical University).Polink-2 plus polymer HRP detection system for goat primary antibody.and 3,3,-Diaminobenzidine tetrahydrochloride substrate kit, Immunohistochemistry kit (from ZSGB-BIO) 2、perfusion and fixation:the rats were taken firstly based anesthesi in the cylinder by Ether, and then was carried out intraperitoneal anesthesia by chloral hydrate(10%), Opened the chest with scissors, with the puncture needle from the left ventricle to ascending aorta, cut the right atrial appendage, first washed with 150ml NaCL(0.9%) quick and perfusated paraformaldehyde(4%) in PBS 300ml, was cut cranial brain and placed in the PBS overnight at 4℃. It was cut into slice serial coronal sections in the vibrating slicer, it be selected the slice with the hippocampus, placed in 0.01mol/L of PBS(PH7.4) solution. 3、immunohistochemistry:The experiments was used to be two-step immunohistochemical staining. 4、statistical analysis:It was observed In Nikon (ECLIPSE80i) by fluorescence microscope image analyzer and the image analysis software with their own analysis of the data. Localization of nuclei of light depend on The Rat Brain in stereotaxic coordinates (third edition).It was observed that the hippocampal area and the 5-HT-positive nerve cells at the low microscope, It was counted 5-HT-positive neurons in the hippocampus CA1, CA2 and CA3 areas in the 10×20 light microscope.It was Observed that 5-HT positive nerve fiber terminals at high he low microscope.The data analysises with the soft SPSS16.5.
Result:At low light microscope:1.The 5-HT immunoreactive product was brown in the hippocampus,a large number of 5-HT positive neurons can be discoveried, positive products were located around the nucleus, the nuclear transparency has not significant stained.2.Immunoreactive cells was band in the hippocampal pyramidal layer of the distribution 3.Counting in 20×10 light microscope immunoreactive cell bodies of CA2 area is the most, followed in the CA1 area, CA3 area are least. there are significant differences by statistical analysis among the CA1, CA2 and CA3 area the number of positive neurons, CA1>CA3, CA2>CA3 (P<0.01).4.The cells of CA3 area is larger than other regions, but weaker staining than the CA1 area. At the high microscope: 1.It shows that more immune 5-HT-positive nerve fibers and terminal 5-HT nerve fibers were beaded terminals (Figure 2b,3b, 4b).2.The positive neurons were round or oval.Otherwise,at the light microscope,the control sections have no expression of anti-5-HT immunoreactive cell body and anti-5-HT immunoreactive nerve fiber terminals in CA1, CA2 and CA3 areas.Its mean values are 5.60±1.075, 5.70±1.252,3.50±1.269.
Conclusion:1.There exist 5-HT nerve fiber terminals and cell bodies in the CA1,CA2 and CA3 of hippocampus.2.The expression of 5-HT immunoreactive products in CA1, CA2 and CA3 areas is uneven, the number of positive neurons is CA1>CA3,CA2>CA3.We conclude that 5-HT neurons may play a role as interneurons in hippocampus
引文
1.许绍芬主编.神经生物学[M].复旦大学出版社,上海,第二版.1999：79-86,389-400.
2.韩太真,吴馥梅主编.学习与记忆的神经生物学[M].北京医科大学,中国协和医科大学联合出版社.北京1998：162-174.
3.包新民,舒斯云.纹状体边缘区的结构和功能研究进展[J].第一军医大学学报,2002,22(4)：289-293.
4. Perez-GarciaG,MenesesA.Memorytime-course:mRNA5-HT1Aand5-HT7 receptors[J].BehavBrainRes.2009Aug4;202(1):102-13.
5. Sarlcisyan G, Hexlund PB.The 5-HT receptor is involved in allocentric spatial memory in formation processing[J]BehavBrainRes.2009Aug24,202(1):26-31
6. Manuel-Apdinar L,Rocha L,Pascoe D. Modifications of 5-HT4 receptor expression in rat brain during memory consolidation[J]. Brain Res 2005 Apr5, 1042(1):73-81.
7. Meneses A.Role of 5-HT6 receptors in memory formation[J].Drug News Perspect.2001,14(7):396-400.
8.周舒,娄艾琳主编.5-羟色胺的生理和病理生理[M],人民卫生出版社,第一版1988,82-88.
9. Perez-garcia GS, Meneses A. Effects of the potential 5-HT7 receptor agonist AS in an autoshaping learning task[J]. Behav Brain Res,2005,163(1):136-140.
10. Perez-garciaG,Gonzalez-EspinosaC, MenesesA. An mRNA expression analysis of stimulation and blockade of 5-HT7 receptors during memory consolidation [J] Behav Brain Res,2006,169(1):83-89.
11.罗学港主编.神经科学基础[M],中南大学出版社,第一版,2002：46.
12.丁斐主编.神经生物学[M].科学出版社,北京,第一版.007：83-94.
13.阮怀珍,蔡文琴主编.医学神经生物学基础[M]第四军医大学出版社,第一版2006：48.
14.高殿帅,张凤真主编,神经生物学基础[M].第二军医大学出版社第一版上海2006,134-145.
15.阮迪云,寿天德编著.神经生理学[M]中国科学技术大学出版社,合肥199：190-196.
16. Medina JH,IzquierdoI.Retrograde messengers,long-term potentiation and memory.Brain Research Reviews,1995,(1):185-194.
17. LynchMA.Age-related impairment in LTP in hippocampus. Progress in Neurobiology,1998,56:571-589.
18. S.W.Jones and P.R.Adams. The M-current and other potassium currents of vertebrate neurons. In Neuromodulation:The Biochemical Control of Neuronal Excitability,L.K.Kaczmarek and I.B.levitan(Eds).New York:Oxford University Press.1987,159-186.
19. U.Larkman and J.B.Jack. Synaptic Plasticity:Hippocampal LTP Curr.Opin[J]. Neurobiol.1995,5:324-334.
20. C.A.Barnes. Involvement of LTP in memory:Are we searching under the street-light[J]. Neuron,1995,15:751-754.
21.R.J.Knox, E.A. Quattrocki,J.A.Connor, and L.K.Kaczmarek. Recruitment of calcium channels during rapid formation of putative neuropeptide release sites in isolated Aplysia neurons[J]. Neuron 1992 8:883-889.
22. E.S. Levitan and I.B.levitan.Serotonin acting via cyclic AMP enhances both the hyperpolarizing and depolarizing phases of bursting pacemaker activity in the Aplysia neuron R15.J. Neurosci,1988,8:1152-1161.
23. umann,W.A.CatterallandT. Scheuer. Functional modulation of brain sodium channels by protein kinase C phosphorylation.Science.1991;254:115-118.
24. F.BearandR.C.Malenka.Synapticplasticity:LTPandLTD.Curr.Opin.Neurobiol.1994 ;4:389-399.
25. A.Frank and M.E. Greenberg.CREB:A mediator of Long-term memory from mollusks to mammals.Cell.1994,79:5-8.
26. W.West,R.Numann,B.J.Murphy,T.Scheuer,andW.A.Catterall.A-phosphorylation site in the sodium channel required for modulation by protein kinase C. Science 1991;2254:866-868.
27. J.Dezazzo and T.Tully. Dissection of memory formation:From behavioral phearmacology to molecular genetics. Trends Neurosci.1995,18:212-218.
28. J.Greenspan. Files, genes,learning and memory.Neuron.1995; 15:747-750.
29.阮怀珍,蔡文琴主编.医学神经生物学基础[M].第四军医大学出版社,第一版2006：48.
30.美Gordonm.sheperd著,蔡南山,戴鸿佐,张淑赋等编译.神经生物学[M].复旦大学出版社,上海,第二版.1990：436.
31.张中启,罗质璞,学习记忆的胆碱能机制与去甲肾上腺素能和5-羟色胺能介质系统的关系[J].中国药理学通报.1994；109(2)：81-83.
32.付元山,王滨,马晓凯等,N-甲基-D-天冬氨酸A/B受体亚型在大鼠丘脑前核和扣带后回的表达[J].中国组织工程研究与临床康复.2007；11(13)：507-509.
33. RolandJJ, SavageLM. Blocking GABA-A receptors in the medial septum enhances hippocampal acetylcholine release and behavior in a rat model of diencephalic amnesia[J]. Pharmacol Biochem Behav.2009;9(3):480-487.
34. Dashniani MG, Beseliia GV, Maqlakelidze GA et al. Effect of the selective lesions of cholinergic septohippocampal neurons on different forms of memory and learning process[J]. Georqian Med new 2009; 166:81-85.
35.王振江,殷桃花,沈维高等。大鼠在学习记忆时海马Ach和Ach能纤维的变化[J].北华大学学报(自然科学版)[J].2008；3：236-238.
1.许绍芬主编.神经生物学[M].复旦大学出版社,上海,第二版.1999：79-86.389-400.
2.韩太真,吴馥梅主编.学习与记忆的神经生物学[M].北京医科大学,中国协和医科大学联合出版社.北京1998：162-174.
3.韩济生主编.神经科学原理[M].北京医科大学出版社,北京,第二版.1999：504-523.
4. Hoyer, Martin GR. Classifiation and nomenclature of 5-HT receptors:a comment on current issues [J]. Behav Brain Res,1996;73:263-268.
5. Filip M, Bader M.Overview on 5-HT receptors and their role in physiology and pathology of the central nervous system [J]. Pharmacol Rep.2009;61(5):761-777.
6. Rigbi A.Yakir A,Kanyas K,et al. Furthe support for a role of the His452Tyr variant in 5-HT2A receptor gene in memory function in human[J]. Int J Neuropsychopharmacol,2009;12, (5):723-725.
7. McCann UD, RicaurteGA. Effectof(+/_)3,4-methyl enedioxy methamphe tamine (NMDA)on sleep and circadian rhythms[J].Scientific WordJournal,2007; 2(7): 231-238.
8. Baxter G, Kennette G, Blaney F,et al.5-HT2 receptor subtypes:a family re-united? [J]. Trends Pharmacol Sci,1995,16:105-110.
9. Parker RMC,Bentley KR,Barnes NM. Allosteric modulation of 5-HT3 receptors: focus on alcohols and anaesthetic agents[J].Trends Pharmacol Sci,1996,17:95-99.
10. PeroutkaSJ,5-HTreceptor:past,presentandfuture[J].TrendsNeurosci,1995,18(2):68-69.
11.包新民,舒斯云.纹状体边缘区的结构和功能研究进展[J].第一军医大学学报(JFirst Mil Med Univ),2002;22(4):289-293.
12.张魁华,舒斯云,包新民等大鼠纹状体边缘区内5-HT2A受体的分布[J].第一军医大学学报(J First Mil Med Univ) 2000;20(3):228-229.
13. Barzilai A, Kennedy TE, Sweatt JD, et al.5-HT modulates protein synthesis and the expression of specific protein during long-term facilitation in Aplysia sensory neurons[J].Neuron,1989;2:1577-1586.
14. Alger BE, Teyler TJ. Long-Term and short-term plasticity in the CA1,CA3 and dentate region of the rat hippocampal slice[J]. Brain Res.1976; 110:463.
15. JiJ,MarenS.Differential role for hippocampal area CA1 and CA3 in the contextual encoding and retrieval of extinguish fear[J].Learn Mem.2008;15(4):244-251.
16. InahLee,GeetaRao,JamesJKnierim. A double dissociation between hippocampal subfields:Differential time course of CA3 and CA1 place cells for processing change environment[J]. Neuron,2004;42(5):803-815.
17.Morioka M, Nagahiros, Fukunaga K, et al. Calcineurin in the adult rat hippocampus:different distribution in CA1 and CA3 subfields[J]. Neuroscience, 1997,78(3):673-684.
18. MercerA, TriggHL,ThomsonAM. Characterization of neurons in the CA2 subfield of the adult rat hippocampus [J]. Neurosci,2007,27(27):7329-7338.
19. A.Frank and M.E. Greenberg.CREB:A mediator of Long-term memory from mollusks to mammals [J].Cell,1994; 79:5-8.
20.张中启,罗质璞.学习记忆的胆碱能机制与去甲肾上腺素能和5-羟色胺能介质系统的关系.中国药理学通报[J].1994,109(2)：81-83
21. McBainCJ,MayerML.N-methyl-D-aspartic acid receptor structure and function. Physiol Rev,1994,74:723-760.
22. RolandJJ,Savage LM.Blocking GABA-A receptors in the medial septum enhances hippocampal acetylcholine release and behavior in a rat model of diencephalic amnesia[J]. Pharmacol Biochem Behav.2009,May,9(3):480-487.
23. U.Larkman andJ.B.Jack. Synaptic Plasticity:Hippocampal LTP. Curr. Opin [J]. Neurobiol.1995(5):324-334.
24. Lynch MA. Age-related impairment in LTP in hippocampus.Progress in Neurobio-logy,1998,56:571-589.
25.DashnianiMG,BeseliiaGV,MaqlakelidzeGA et al. Effect of the selective lesions of cholinergic septo hippocampal neurons on different forms of memory and learning process.[J] Georqian Med new 2009 Jan;166:81-85.
26. U.LarkmanandJ.B.Jack.Synaptic Plasticity:Hippocampal LTP. Curr. Opin [J]. Neurobiol.1995(5):324-334.
27. AndersonP, BlissVP, SkredeKK. Lamellar organization of hippocampal excitory pathways[J]. Expl Barin Res,1971;13:222-238.
28. OgrenSO. Evidence for a role of brain serotonergic neurotransmission in avoidance learning[J]. Acta Physiol Scand Supp,1985,544:1-7.
29.洪燕,王冬兰,李树田等.维生素B6缺乏对大鼠学习记忆的影响及有关机制的探讨[J].中国行为医学科学,2000,9(2)：94-96.
30.张工桥,刘德华,何鹏.锰对小学生学习能力的影响初探[J].中华预防医学杂志, ]995,29(3):156-158.
31.谭永霞,李玲,陈景藻等.8Hz次声对大鼠海马和颞叶皮层5-HT表达的响.Chin J Rehabil Theory Practice,2004,10(2):76-78.
2.韩太真,吴馥梅主编.学习与记忆的神经生物学[M].北京医科大学,中国协和医科大学联合出版社.北京1998：162-174.
3.包新民,舒斯云.纹状体边缘区的结构和功能研究进展[J].第一军医大学学报,2002,22(4)：289-293.
4. Perez-GarciaG,MenesesA.Memorytime-course:mRNA5-HT1Aand5-HT7 receptors[J].BehavBrainRes.2009Aug4;202(1):102-13.
5. Sarlcisyan G, Hexlund PB.The 5-HT receptor is involved in allocentric spatial memory in formation processing[J]BehavBrainRes.2009Aug24,202(1):26-31
6. Manuel-Apdinar L,Rocha L,Pascoe D. Modifications of 5-HT4 receptor expression in rat brain during memory consolidation[J]. Brain Res 2005 Apr5, 1042(1):73-81.
7. Meneses A.Role of 5-HT6 receptors in memory formation[J].Drug News Perspect.2001,14(7):396-400.
8.周舒,娄艾琳主编.5-羟色胺的生理和病理生理[M],人民卫生出版社,第一版1988,82-88.
9. Perez-garcia GS, Meneses A. Effects of the potential 5-HT7 receptor agonist AS in an autoshaping learning task[J]. Behav Brain Res,2005,163(1):136-140.
10. Perez-garciaG,Gonzalez-EspinosaC, MenesesA. An mRNA expression analysis of stimulation and blockade of 5-HT7 receptors during memory consolidation [J] Behav Brain Res,2006,169(1):83-89.
11.罗学港主编.神经科学基础[M],中南大学出版社,第一版,2002：46.
12.丁斐主编.神经生物学[M].科学出版社,北京,第一版.007：83-94.
13.阮怀珍,蔡文琴主编.医学神经生物学基础[M]第四军医大学出版社,第一版2006：48.
14.高殿帅,张凤真主编,神经生物学基础[M].第二军医大学出版社第一版上海2006,134-145.
15.阮迪云,寿天德编著.神经生理学[M]中国科学技术大学出版社,合肥199：190-196.
16. Medina JH,IzquierdoI.Retrograde messengers,long-term potentiation and memory.Brain Research Reviews,1995,(1):185-194.
17. LynchMA.Age-related impairment in LTP in hippocampus. Progress in Neurobiology,1998,56:571-589.
18. S.W.Jones and P.R.Adams. The M-current and other potassium currents of vertebrate neurons. In Neuromodulation:The Biochemical Control of Neuronal Excitability,L.K.Kaczmarek and I.B.levitan(Eds).New York:Oxford University Press.1987,159-186.
19. U.Larkman and J.B.Jack. Synaptic Plasticity:Hippocampal LTP Curr.Opin[J]. Neurobiol.1995,5:324-334.
20. C.A.Barnes. Involvement of LTP in memory:Are we searching under the street-light[J]. Neuron,1995,15:751-754.
21.R.J.Knox, E.A. Quattrocki,J.A.Connor, and L.K.Kaczmarek. Recruitment of calcium channels during rapid formation of putative neuropeptide release sites in isolated Aplysia neurons[J]. Neuron 1992 8:883-889.
22. E.S. Levitan and I.B.levitan.Serotonin acting via cyclic AMP enhances both the hyperpolarizing and depolarizing phases of bursting pacemaker activity in the Aplysia neuron R15.J. Neurosci,1988,8:1152-1161.
23. umann,W.A.CatterallandT. Scheuer. Functional modulation of brain sodium channels by protein kinase C phosphorylation.Science.1991;254:115-118.
24. F.BearandR.C.Malenka.Synapticplasticity:LTPandLTD.Curr.Opin.Neurobiol.1994 ;4:389-399.
25. A.Frank and M.E. Greenberg.CREB:A mediator of Long-term memory from mollusks to mammals.Cell.1994,79:5-8.
26. W.West,R.Numann,B.J.Murphy,T.Scheuer,andW.A.Catterall.A-phosphorylation site in the sodium channel required for modulation by protein kinase C. Science 1991;2254:866-868.
27. J.Dezazzo and T.Tully. Dissection of memory formation:From behavioral phearmacology to molecular genetics. Trends Neurosci.1995,18:212-218.
28. J.Greenspan. Files, genes,learning and memory.Neuron.1995; 15:747-750.
29.阮怀珍,蔡文琴主编.医学神经生物学基础[M].第四军医大学出版社,第一版2006：48.
30.美Gordonm.sheperd著,蔡南山,戴鸿佐,张淑赋等编译.神经生物学[M].复旦大学出版社,上海,第二版.1990：436.
31.张中启,罗质璞,学习记忆的胆碱能机制与去甲肾上腺素能和5-羟色胺能介质系统的关系[J].中国药理学通报.1994；109(2)：81-83.
32.付元山,王滨,马晓凯等,N-甲基-D-天冬氨酸A/B受体亚型在大鼠丘脑前核和扣带后回的表达[J].中国组织工程研究与临床康复.2007；11(13)：507-509.
33. RolandJJ, SavageLM. Blocking GABA-A receptors in the medial septum enhances hippocampal acetylcholine release and behavior in a rat model of diencephalic amnesia[J]. Pharmacol Biochem Behav.2009;9(3):480-487.
34. Dashniani MG, Beseliia GV, Maqlakelidze GA et al. Effect of the selective lesions of cholinergic septohippocampal neurons on different forms of memory and learning process[J]. Georqian Med new 2009; 166:81-85.
35.王振江,殷桃花,沈维高等。大鼠在学习记忆时海马Ach和Ach能纤维的变化[J].北华大学学报(自然科学版)[J].2008；3：236-238.
1.许绍芬主编.神经生物学[M].复旦大学出版社,上海,第二版.1999：79-86.389-400.
2.韩太真,吴馥梅主编.学习与记忆的神经生物学[M].北京医科大学,中国协和医科大学联合出版社.北京1998：162-174.
3.韩济生主编.神经科学原理[M].北京医科大学出版社,北京,第二版.1999：504-523.
4. Hoyer, Martin GR. Classifiation and nomenclature of 5-HT receptors:a comment on current issues [J]. Behav Brain Res,1996;73:263-268.
5. Filip M, Bader M.Overview on 5-HT receptors and their role in physiology and pathology of the central nervous system [J]. Pharmacol Rep.2009;61(5):761-777.
6. Rigbi A.Yakir A,Kanyas K,et al. Furthe support for a role of the His452Tyr variant in 5-HT2A receptor gene in memory function in human[J]. Int J Neuropsychopharmacol,2009;12, (5):723-725.
7. McCann UD, RicaurteGA. Effectof(+/_)3,4-methyl enedioxy methamphe tamine (NMDA)on sleep and circadian rhythms[J].Scientific WordJournal,2007; 2(7): 231-238.
8. Baxter G, Kennette G, Blaney F,et al.5-HT2 receptor subtypes:a family re-united? [J]. Trends Pharmacol Sci,1995,16:105-110.
9. Parker RMC,Bentley KR,Barnes NM. Allosteric modulation of 5-HT3 receptors: focus on alcohols and anaesthetic agents[J].Trends Pharmacol Sci,1996,17:95-99.
10. PeroutkaSJ,5-HTreceptor:past,presentandfuture[J].TrendsNeurosci,1995,18(2):68-69.
11.包新民,舒斯云.纹状体边缘区的结构和功能研究进展[J].第一军医大学学报(JFirst Mil Med Univ),2002;22(4):289-293.
12.张魁华,舒斯云,包新民等大鼠纹状体边缘区内5-HT2A受体的分布[J].第一军医大学学报(J First Mil Med Univ) 2000;20(3):228-229.
13. Barzilai A, Kennedy TE, Sweatt JD, et al.5-HT modulates protein synthesis and the expression of specific protein during long-term facilitation in Aplysia sensory neurons[J].Neuron,1989;2:1577-1586.
14. Alger BE, Teyler TJ. Long-Term and short-term plasticity in the CA1,CA3 and dentate region of the rat hippocampal slice[J]. Brain Res.1976; 110:463.
15. JiJ,MarenS.Differential role for hippocampal area CA1 and CA3 in the contextual encoding and retrieval of extinguish fear[J].Learn Mem.2008;15(4):244-251.
16. InahLee,GeetaRao,JamesJKnierim. A double dissociation between hippocampal subfields:Differential time course of CA3 and CA1 place cells for processing change environment[J]. Neuron,2004;42(5):803-815.
17.Morioka M, Nagahiros, Fukunaga K, et al. Calcineurin in the adult rat hippocampus:different distribution in CA1 and CA3 subfields[J]. Neuroscience, 1997,78(3):673-684.
18. MercerA, TriggHL,ThomsonAM. Characterization of neurons in the CA2 subfield of the adult rat hippocampus [J]. Neurosci,2007,27(27):7329-7338.
19. A.Frank and M.E. Greenberg.CREB:A mediator of Long-term memory from mollusks to mammals [J].Cell,1994; 79:5-8.
20.张中启,罗质璞.学习记忆的胆碱能机制与去甲肾上腺素能和5-羟色胺能介质系统的关系.中国药理学通报[J].1994,109(2)：81-83
21. McBainCJ,MayerML.N-methyl-D-aspartic acid receptor structure and function. Physiol Rev,1994,74:723-760.
22. RolandJJ,Savage LM.Blocking GABA-A receptors in the medial septum enhances hippocampal acetylcholine release and behavior in a rat model of diencephalic amnesia[J]. Pharmacol Biochem Behav.2009,May,9(3):480-487.
23. U.Larkman andJ.B.Jack. Synaptic Plasticity:Hippocampal LTP. Curr. Opin [J]. Neurobiol.1995(5):324-334.
24. Lynch MA. Age-related impairment in LTP in hippocampus.Progress in Neurobio-logy,1998,56:571-589.
25.DashnianiMG,BeseliiaGV,MaqlakelidzeGA et al. Effect of the selective lesions of cholinergic septo hippocampal neurons on different forms of memory and learning process.[J] Georqian Med new 2009 Jan;166:81-85.
26. U.LarkmanandJ.B.Jack.Synaptic Plasticity:Hippocampal LTP. Curr. Opin [J]. Neurobiol.1995(5):324-334.
27. AndersonP, BlissVP, SkredeKK. Lamellar organization of hippocampal excitory pathways[J]. Expl Barin Res,1971;13:222-238.
28. OgrenSO. Evidence for a role of brain serotonergic neurotransmission in avoidance learning[J]. Acta Physiol Scand Supp,1985,544:1-7.
29.洪燕,王冬兰,李树田等.维生素B6缺乏对大鼠学习记忆的影响及有关机制的探讨[J].中国行为医学科学,2000,9(2)：94-96.
30.张工桥,刘德华,何鹏.锰对小学生学习能力的影响初探[J].中华预防医学杂志, ]995,29(3):156-158.
31.谭永霞,李玲,陈景藻等.8Hz次声对大鼠海马和颞叶皮层5-HT表达的响.Chin J Rehabil Theory Practice,2004,10(2):76-78.