激活大鼠右侧尾壳核重建双侧海马癫痫电网络的细胞电生理机制
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摘要
本工作目的在于探讨强直电刺激大鼠右侧尾壳核(caudate putamen，CPu)重建双侧海马(hippocampus，HPC)癫痫电网络的细胞电生理机制。实验共用雄性SD大鼠101只，体重200～250g。急性强直电刺激(60Hz，2s，0.4～0.6mA)右侧尾壳核(acute tetanization of the right caudate putamen，ATRC)或右背海马(acute tetanization of the right dorsal hippocampus，ATRDH)，同步记录双侧前背HPC神经元单位放电，ATRC同步记录双侧HPC深部电图。比较激活右侧CPu到达双侧HPC或者激活右侧HPC到达双侧HPC时，经历了不同的神经通路长度对HPC癫痫电网络重建过程的影响，以及单个神经元电活动信息编码特征。结果表明：(1)ATRC可以促使HPC癫痫电网络的形成，显现出双侧HPC同步化的癫痫电活动；(2)ATRC和ATRDH均能明显调制单个HPC神经元的紧张式放电成为节律性爆发式放电；ATRC引起的HPC爆发式单位放电每串持续时间即串长(650.738±56.419ms，n=120)长、爆发式放电间期(interbursting interval，IBI，772.600±46.665ms，n=90)短；相反，ATRDH引起HPC的爆发式单位放电特征是串长短(270.612±19.917 ms，n=123)(T=6.353，P＜0.001)、IBI长(1373.663±121.236ms，n=103)(T=4.627，P＜0.001)；(3)ATRC诱发的HPC细胞单位后放电时程长(7.06±0.776s，n=104)、潜伏期也长(8.77±1.231trains，n=30)，而ATRDH诱发的单位后放电时程短(3.93±0.657s，n=33)(T=0.3079，P＜0.001)、潜伏期也短(3.33±0.681trains，n=15)T=3.681，P＜0.001)；(4)ATRC可诱导HPC爆发式单位放电和单位后放电之间的直接转换；(5)ATRC可促进双侧HPC神经元单位电活动的同步化或交互性作用。结果证实：激活CPu-HPC长路径神经通路可导致双侧HPC神经元长时程癫痫相关性电活动的形成，促进HPC癫痫电网络的重建，引发双侧颞叶癫痫的发作。激活右侧CPu，HPC神经元信息编码特征是爆发式单位放电的串长较长，IBI较短，具有神经元癫痫相关性电活动的放大作用；而激活右侧HPC后，HPC神经元信息编码特征是爆发式单位放电串长短，IBI较长，即激活到HPC不同的神经元通路，HPC神经元信息编码特征不同。很可能，激活了的CPu-HPC通路在HPC癫痫电网络病理性神经信息传递中可能起着重要的生物放大器作用。
The purpose was to study the cellular electrophisiological mechanism of epileptic networks in dual hippocampi reestablished by overactivation of the right caudate putamen (CPu). The experiments were performed on 101 male Sprague Dawley rats weighting 200~250g. Acute tetanization (60Hz, 2s, 0.4~0.6mA) of the right caudate putamen (ATRC) or of the right dorsal hippocampus (ATRDH) was administrated to establish rat epilepsy model. A pair of single unit recordings from bilateral hippocampi was simultaneously used to detect the effects of the ATRC or those of the ATRDH, bilateral hippocampal depth electrograhgh were also simultaneously recorded after the ATRC. Neuronal epilepsy-related firing patterns were analyzed according to activated neural pathway length from the RCPu to the dual hippocampi, or from the right dorsal HPC to ipsilateral hippocampal local networks and contralateral HPC. Results demonstrated that: (1) ATRC could facilitate the formation of hippocampal epileptic networks, and presented the synchr
onaztion of epilepsy related electric activities in bilateral hippcampi. (2) The firing pattern of single hippocampal neuron was obviously modulated both by the ATRC and by the ATPDH. There were long duration bursting (650.738?6.419 ms, n=120) with short interbursting interval (IBI)
(772.600 +46.665ms, n=90) of single neuron induced by the ATRC, while short duration bursting (270.612 + 19.917 ms, n=123) (T=6.353, P<0.001)of single neuron with long IBI
(1373.663 ?121.236ms, n=103) (T=4.627, P<0.001)by the ATPDH. (3) There were long duration single unit afterdischarges (7.06 +0.776s, n=104) with long latency (8.77 + 1.231trains, n=30) induced by the ATRC, while short duration single unit afterdischarges
(3.93 + 0.657S, n=33)( T=0.3079, P<0.001)with short latency (3.33+ 0.681trains, n=15) (7=3.681, P0.001) induced by the ATPDH. (4) ATRC could induce the immediate transition between single unit bursting and afterdischarges. (5) Pairs of cellular electric activities in bilateral hippocampi were synchronouse or interactive inhibiting after repeated administration of the ATRC. The results suggest that long duration single unit bursting or afterdischarges in bilateral hippocampi could be brought about by overactivation of
long-distance neural pathway from the right CPu to the dual hippocampi, which might be an important cellular mechanism of hippocampal epileptic networks reconstruction. From these phenomina the following conclusion can be drawn that there was different information encoding charisteristic when different neural pathway was activated. The activated CPu-HPC functional neural pathway might act as the amplifier of the signal of epilepsy-related activities of single neuron in bilateral hippocampi.
The purpose was to study the cellular electrophisiological mechanism of epileptic networks in dual hippocampi reestablished by overactivation of the right caudate putamen (CPu). The experiments were performed on 101 male Sprague Dawley rats weighting 200~250g. Acute tetanization (60Hz, 2s, 0.4~0.6mA) of the right caudate putamen (ATRC) or of the right dorsal hippocampus (ATRDH) was administrated to establish rat epilepsy model. A pair of single unit recordings from bilateral hippocampi was simultaneously used to detect the effects of the ATRC or those of the ATRDH, bilateral hippocampal depth electrograhgh were also simultaneously recorded after the ATRC. Neuronal epilepsy-related firing patterns were analyzed according to activated neural pathway length from the RCPu to the dual hippocampi, or from the right dorsal HPC to ipsilateral hippocampal local networks and contralateral HPC. Results demonstrated that: (1) ATRC could facilitate the formation of hippocampal epileptic networks, and presented the synchr
onaztion of epilepsy related electric activities in bilateral hippcampi. (2) The firing pattern of single hippocampal neuron was obviously modulated both by the ATRC and by the ATPDH. There were long duration bursting (650.738?6.419 ms, n=120) with short interbursting interval (IBI)
(772.600 +46.665ms, n=90) of single neuron induced by the ATRC, while short duration bursting (270.612 + 19.917 ms, n=123) (T=6.353, P<0.001)of single neuron with long IBI
(1373.663 ?121.236ms, n=103) (T=4.627, P<0.001)by the ATPDH. (3) There were long duration single unit afterdischarges (7.06 +0.776s, n=104) with long latency (8.77 + 1.231trains, n=30) induced by the ATRC, while short duration single unit afterdischarges
(3.93 + 0.657S, n=33)( T=0.3079, P<0.001)with short latency (3.33+ 0.681trains, n=15) (7=3.681, P0.001) induced by the ATPDH. (4) ATRC could induce the immediate transition between single unit bursting and afterdischarges. (5) Pairs of cellular electric activities in bilateral hippocampi were synchronouse or interactive inhibiting after repeated administration of the ATRC. The results suggest that long duration single unit bursting or afterdischarges in bilateral hippocampi could be brought about by overactivation of
long-distance neural pathway from the right CPu to the dual hippocampi, which might be an important cellular mechanism of hippocampal epileptic networks reconstruction. From these phenomina the following conclusion can be drawn that there was different information encoding charisteristic when different neural pathway was activated. The activated CPu-HPC functional neural pathway might act as the amplifier of the signal of epilepsy-related activities of single neuron in bilateral hippocampi.
引文
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25. Chang Q, Gold PE. Intra-hippocampal lidocaine injections impair acquisition of a place task and facilitate acquisition of a response task in rats. Behav Brain Res, 2003, 144(1-2): 19-24
26. Shu SY, Wu YM, Bao XM, Leonard B. Interactions among memory-related centers in the brain. J Neurosci Res. 2003, 71(5):609-616.
27. Poldrack RA, Packard MG. Competition among multiple memory systems: converging evidence from animal and human brain studies. Neuropsychologia, 2003, 41(3):245-251.
28. Chang Q, Gold PE. Switching memory systems during learning: changes inpattems of brain acetylcholine release in the hippocampus and striatum in rats. J Neurosci, 2003, 23(7):3001-3005.
29. Maguire EA, Burgess N, Donnett JG, Frackowiak RS, Frith CD, O'Keefe J. Knowing where and getting there: a human navigation network. Science, 1998, 280(5365): 921～924.
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2. Dagher A, Owen AM, Boecker H, Brooks DJ. The role of the striatum and hippocampus in planning: a PET activation. study in Parkinson's disease. Brain, 200. 1, 124(Pt 5): 1020-1032.
3. Dreifuss S, Vingerhoets FJ, Lazeyras F, Andino SG, Spinelli L, Delavelle J, Seeck M. Volumetric measurements of subcortical nuclei in patients with temporal lobe epilepsy. Neurology, 2001, 57(9):1636-1641.
4. Sasaki M, Matsuda H, Omura I, Sugai K, Hashimoto T. Transient seizure disappearance due to bilateral striatal necrosis in a patient with intractable epilepsy. Brain Dev, 2000, 22(1):50-55.
5. Fujikawa DG. The temporal evolution of neuronal damage from pilocarpine-induced status epilepticus. Brain Res, 1996, 725(1): 11-22.
6. Klitgaard H, Matagne A, Grimee R, Vanneste-Goemaere J, Margineanu DG. Electrophysiological, neurochemical and regional effects of Levetiracetam in the rat pilocarpine model of temporal lobe epilepsy. Seizure, 2003, 12(2):92-100.
7. Mizobuchi M, Sumi Y, Sako K, Nihira A, Nakagawara J. Putaminal hyperperfusion in dystonic posturing on subtracted SPECT: a case report. Ann Nucl Med, 2001, 15(3):255-257.
8. Sabatino M, Ferraro G, Caravaglios G, Sardo P, Aloisio A, Iurato L, La grutta V. involvement of a GABAergic neurotransmission. Neurophysiol Clin, 1992, 22(1)3-16.
9. Chkhenkeli SA, Chkhenkeii IS. Effects of therapeutic stimulation of nucleus caudatus on epileptical electrical activity of brain in patients with intractable epilepsy. Stereotact Funct Neurosurg, 1997, 69(1-4 Pt 2):221-224.
10. Sabatino M, Ferraro G, Liberti G, Vella N, La Grutta V. Striatal and septal influence on
hippocampal theta and spikes in the cat. Neurosci Lett, 1985, 61(1-2):55-59.
11. Sabatino M, La Grutta V, Ferraro G, La Grutta G. Relations between basal ganglia and hippocampus: action of substantia nigra and pallidum. Rev Electroencephalogr Neurophysiol Clin, 1986, 16(2): 179-190.
12. Sabatino M, Ferraro G, Vella N, La Grutta V. An electrophysiological study of habenular influence on hippocampus. Neurosci Lett, 1987, 78(1):75-79.
13. Rektor I, Kuba R, Brazdil M. Interictal and ictal activity in the basal ganglia: an EEG study in patients with temporal lobe epilepsy. Epilepsia 2001, 43(3):253-262.
14．韩丹，范伟，张先荣，邹祖玉，曾俊．强直电刺激右侧尾壳核对大鼠海马、中部颞叶新皮质电图的影响．中国应用生理学杂志，2002，18(3)：239～244．
15．尹世金，韩丹，黎莉．强直电刺激右背海马诱发双侧海马神经元癫痫相关性单位放电特征．中国应用生理学杂志，2001，17(3)：262～266．
16．Han D(韩丹)，Zhang XR(张先荣)，Tang YF(唐岳枫)，Liu ML(刘买利)，Yin SJ(尹世金)．Characteristic behavioral seizures and abnormal signal asymmetry of magnetic resonance imaging in an electrogenic rat model 0f chronic epilepsy．Acta Physiol Sin(生理学报)，200 1，53(3)：224～230．
17．张先荣，韩丹，唐岳枫，刘买利，王晓云．慢性颞叶癫痫大鼠行为、电图发作和核磁共振研究——海马-内嗅皮质-颞叶新皮质通路．中国应用生理学杂志，2000，16(4)：289～293．
18．臧颖，韩丹，杨运煌，刘买利，邹祖玉．核磁共振检测大鼠早期癫痫源性脑损伤的动态发展特征．生理学报，2002，54(3)：201～207．
19. Zhang XR, Han D, Tang YF, Liu ML, Yin SJ. Possible role of dentate gyrus in generation of rat temporal lobe epilepsy induced by electrical stimulation. Acta Physiologica Sinica, 2001, 53(3): 235～239.
20．刘慧浪，韩丹，张先荣，邹祖玉．刺激大鼠右侧胼胝体激活对侧尾壳核-海马癫痫相关性神经网络．中国应用生理学杂志，2003，19(2)：165～170．
21．包新民，舒斯云．大鼠脑立体定位图谱，北京：人民卫生出版社，1991．
22．彭莉辉，吴鸿修，庄峻，尹世金，韩丹，刘维泽，汤剑清．神经电生理信号多通道同步采集和分析系统．生理学报，2001，53(1)：79～82．
23. Colder BW, Wilson CL, Frysinger RC, Chao LC, Harper RM, AND Engel J Jr. Neuronal synchrony in relation to burst discharge in epileptic human temporal lobes. J Neurophysiol, 1996, 75(6):2496～2508.
24. Groenewegen HJ, Vermeulen-Van der Zee E, te Kortschot A, Witter MP. Organization of the projections from the subiculum to the ventral striatum in the rat. A study using anterograde transport of Phaseolus vulgaris leucoagglutinin. Neuroscience, 1987, 23(1): 103～120.
25. Chang Q, Gold PE. Intra-hippocampal lidocaine injections impair acquisition of a place task and facilitate acquisition of a response task in rats. Behav Brain Res, 2003, 144(1-2): 19-24
26. Shu SY, Wu YM, Bao XM, Leonard B. Interactions among memory-related centers in the brain. J Neurosci Res. 2003, 71(5):609-616.
27. Poldrack RA, Packard MG. Competition among multiple memory systems: converging evidence from animal and human brain studies. Neuropsychologia, 2003, 41(3):245-251.
28. Chang Q, Gold PE. Switching memory systems during learning: changes inpattems of brain acetylcholine release in the hippocampus and striatum in rats. J Neurosci, 2003, 23(7):3001-3005.
29. Maguire EA, Burgess N, Donnett JG, Frackowiak RS, Frith CD, O'Keefe J. Knowing where and getting there: a human navigation network. Science, 1998, 280(5365): 921～924.
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