Long-term potentiation-based screening identifies neuronal PYGM as a synaptic plasticity regulator participating in Alzheimer's disease

Synaptic dysfunction is an important pathological hallmark and cause of Alzheimer's disease(AD).High-frequency stimulation(HFS)-induced long-term potentiation(LTP)has been widely used to study synaptic plasticity,with impaired LTP found to be associated with AD.However,the exact molecular mechanism underlying synaptic plasticity has yet to be completely elucidated.Whether genes regulating synaptic plasticity are altered in AD and contribute to disease onset also remains unclear.Herein,we induced LTP in the hippocampal CA1 region of wildtype(WT)and AD model mice by administering HFS to the CA3 region and then studied transcriptome changes in the CA1 region.We identified 89 genes that may participate in normal synaptic plasticity by screening HFS-induced differentially expressed genes(DEGs)in mice with normal LTP,and 43 genes that may contribute to synaptic dysfunction in AD by comparing HFS-induced DEGs in mice with normal LTP and AD mice with impaired LTP.We further refined the 43 genes down to 14 by screening for genes with altered expression in pathological-stage AD mice without HFS induction.Among them,we found that the expression of Pygm,which catabolizes glycogen,was also decreased in AD patients.We further demonstrated that down-regulation of PYGM in neurons impaired synaptic plasticity and cognition in WT mice,while its overexpression attenuated synaptic dysfunction and cognitive deficits in AD mice.Moreover,we showed that PYGM directly regulated energy generation in neurons.Our study not only indicates that PYGM-mediated energy production in neurons plays an important role in synaptic function,but also provides a novel LTP-based strategy to systematically identify genes regulating synaptic plasticity under physiological and pathological conditions.

3'-Deoxyadenosin alleviates methamphetamine-induced aberrant synaptic plasticity and seeking behavior by inhibiting the NLRP3 inflammasome

Methamphetamine addiction is a brain disorder characterized by persistent drug-seeking behavior, which has been linked with aberrant synaptic plasticity. An increasing body of evidence suggests that aberrant synaptic plasticity is associated with the activation of the NOD-like receptor family pyrin domain containing-3(NLRP3) inflammasome. 3′-Deoxyadenosin, an active component of the Chinese fungus Cordyceps militaris, has strong anti-inflammatory effects. However, whether 3′-deoxyadenosin attenuates methamphetamine-induced aberrant synaptic plasticity via an NLRP3-mediated inflammatory mechanism remains unclear. We first observed that 3′-deoxyadenosin attenuated conditioned place preference scores in methamphetamine-treated mice and decreased the expression of c-fos in hippocampal neurons. Furthermore, we found that 3′-deoxyadenosin reduced the aberrant potentiation of glutamatergic transmission and restored the methamphetamine-induced impairment of synaptic plasticity. We also found that 3′-deoxyadenosin decreased the expression of NLRP3 and neuronal injury. Importantly, a direct NLRP3 deficiency reduced methamphetamine-induced seeking behavior, attenuated the impaired synaptic plasticity, and prevented neuronal damage. Finally, NLRP3 activation reversed the effect of 3′-deoxyadenosin on behavior and synaptic plasticity, suggesting that the anti-neuroinflammatory mechanism of 3′-deoxyadenosin on aberrant synaptic plasticity reduces methamphetamine-induced seeking behavior. Taken together, 3′-deoxyadenosin alleviates methamphetamine-induced aberrant synaptic plasticity and seeking behavior by inhibiting the NLRP3 inflammasome.

Glutamate receptor delocalization in postsynaptic membrane and reduced hippocampal synaptic plasticity in the early stage of Alzheimer's disease

Mounting evidence suggests that synaptic plasticity provides the cellular biological basis of learning and memory, and plasticity deficits play a key role in dementia caused by Alzheimer's disease. However, the mechanisms by which synaptic dysfunction contributes to the pathogenesis of Alzheimer's disease remain unclear. In the present study, Alzheimer's disease transgenic mice were used to determine the relationship between decreased hippocampal synaptic plasticity and pathological changes and cognitive-behavioral deterioration, as well as possible mechanisms underlying decreased synaptic plasticity in the early stages of Alzheimer's disease-like diseases. APP/PS1 double transgenic(5 XFAD; Jackson Laboratory) mice and their littermates(wild-type, controls) were used in this study. Additional 6-weekold and 10-week-old 5 XFAD mice and wild-type mice were used for electrophysiological recording of hippocampal dentate gyrus. For10-week-old 5 XFAD mice and wild-type mice, the left hippocampus was used for electrophysiological recording, and the right hippocampus was used for biochemical experiments or immunohistochemical staining to observe synaptophysin levels and amyloid beta deposition levels. The results revealed that, compared with wild-type mice, 6-week-old 5 XFAD mice exhibited unaltered long-term potentiation in the hippocampal dentate gyrus. Another set of 5 XFAD mice began to show attenuation at the age of 10 weeks, and a large quantity of amyloid beta protein was accumulated in hippocampal cells. The location of α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptor and N-methyl-D-aspartic acid receptor subunits in synaptosomes was decreased. These findings indicate that the delocalization of postsynaptic glutamate receptors and an associated decline in synaptic plasticity may be key mechanisms in the early onset of Alzheimer's disease. The use and care of animals were in strict accordance with the ethical standards of the Animal Ethics Committee of Capital Medical University,China on December 17, 2015(approval No. AEEI-2015-182).

Basic roles of key molecules connected with NMDAR signaling pathway on regulating learning and memory and synaptic plasticity

With key roles in essential brain functions ranging from the long-term potentiation(LTP) to synaptic plasticity,the N-methyl-D-aspartic acid receptor(NMDAR) can be considered as one of the fundamental glutamate receptors in the central nervous system.The role of NMDA R was first identified in synaptic plasticity and has been extensively studied.Some molecules,such as Ca^(2+),postsynaptic density 95(PSD-95),calcium/calmodulin-dependent protein kinase II(Ca MK II),protein kinase A(PKA),mitogen-activated protein kinase(MAPK) and cyclic adenosine monophosphate(c AMP) responsive element binding protein(CREB),are of special importance in learning and memory.This review mainly focused on the new research of key molecules connected with learning and memory,which played important roles in the NMDAR signaling pathway.

Paired associative stimulation improves synaptic plasticity and functional outcomes after cerebral ischemia

Paired associative stimulation is a relatively new non-invasive brain stimulation technique that combines transcranial magnetic stimulation and peripheral nerve stimulation. The effects of paired associative stimulation on the excitability of the cerebral cortex can vary according to the time interval between the transcranial magnetic stimulation and peripheral nerve stimulation. We established a model of cerebral ischemia in rats via transient middle cerebral artery occlusion. We administered paired associative stimulation with a frequency of 0.05 Hz 90 times over 4 weeks. We then evaluated spatial learning and memory using the Morris water maze. Changes in the cerebral ultra-structure and synaptic plasticity were assessed via transmission electron microscopy and a 64-channel multi-electrode array. We measured mRNA and protein expression levels of brain-derived neurotrophic factor and N-methyl-D-aspartate receptor 1 in the hippocampus using a real-time polymerase chain reaction and western blot assay. Paired associative stimulation treatment significantly improved learning and memory in rats subjected to cerebral ischemia. The ultra-structures of synapses in the CA1 area of the hippocampus in rats subjected to cerebral ischemia were restored by paired associative stimulation. Long-term potentiation at synapses in the CA3 and CA1 regions of the hippocampus was enhanced as well. The protein and mRNA expression of brain-derived neurotrophic factor and N-methyl-D-aspartate receptor 1 increased after paired associative stimulation treatment. These data indicate that paired associative stimulation can protect cog-nition after cerebral ischemia. The observed effect may be mediated by increases in the mRNA and protein expression of brain-derived neurotrophic factor and N-methyl-D-aspartate receptor 1, and by enhanced synaptic plasticity in the CA1 area of the hippocampus. The animal experiments were approved by the Animal Ethics Committee of Tongji Medical College, Huazhong University of Science & Technology, China(approval No. TJ-A20151102) on July 11, 2015.

Cranial irradiation impairs intrinsic excitability and synaptic plasticity of hippocampal CA1 pyramidal neurons with implications for cognitive function

Radiation therapy is a standard treatment for head and neck tumors.However,patients often exhibit cognitive impairments following radiation therapy.Previous studies have revealed that hippocampal dysfunction,specifically abnormal hippocampal neurogenesis or neuroinflammation,plays a key role in radiation-induced cognitive impairment.However,the long-term effects of radiation with respect to the electrophysiological adaptation of hippocampal neurons remain poorly characterized.We found that mice exhibited cognitive impairment 3 months after undergoing 10 minutes of cranial irradiation at a dose rate of 3 Gy/min.Furthermore,we observed a remarkable reduction in spike firing and excitatory synaptic input,as well as greatly enhanced inhibitory inputs,in hippocampal CA1 pyramidal neurons.Corresponding to the electrophysiological adaptation,we found reduced expression of synaptic plasticity marker VGLUT1 and increased expression of VGAT.Furthermore,in irradiated mice,long-term potentiation in the hippocampus was weakened and GluR1 expression was inhibited.These findings suggest that radiation can impair intrinsic excitability and synaptic plasticity in hippocampal CA1 pyramidal neurons.

Curcumin improves synaptic plasticity impairment induced by HIV-1gp120 V3 loop

Curcumin has been shown to significantly improve spatial memory impairment induced by HIV-1 gp 120 V3 in rats, but the electrophysiological mechanism remains unknown. Using extracellular microelectrode recording techniques, this study confirmed that the gp120 V3 loop could suppress long-term potentiation in the rat hippocampal CA1 region and synaptic plasticity, and that curcumin could antagonize these inhibitory effects. Using a Fura-2/AM calcium ion probe, we found that curcumin resisted the effects of the gp120 V3 loop on hippocampal synaptosomes and decreased Ca2＋ concentration in synaptosomes. This effect of curcumin was identical to nimodipine, suggesting that curcumin improved the inhibitory effects of gpl20 on synaptic plasticity, ameliorated damage caused to the central nervous system, and might be a potential neuroprotective drug.

How Spines Cross-Talk： Compartmental Model of Heterosynaptic Plasticity

This study addresses the fundamental principle of inter-synaptic interactions in synaptic cross-talk through homosynaptic and heterosynaptic plasticity by studying the intrinsic calcium signaling dynamics in spines. Beyond the calcium influx into synapse through voltage gated calcium channels （VGCCs） and N-methyl-D-aspartate （NNMDA） receptors, the function of calcium released from internal store in mediating inter-synaptic cross-talk has barely been modeled. This work investigates how different sources of calcium contribute to inter-synaptic cross-talk and synaptic clustering. Based on experimental observations, we developed a mathematical model in one dimensional system with uniform distribution of spines with the connected dendrite. We modeled the biophysical process of calcium induced calcium release （CICR） in the dendritic smooth endoplasmic reticulum （SER）. Our model compared distinct roles of calcium diffusion, back propagated action potentials （bAPs） and CICR played in synaptic clustering and inter-synaptic cross-talk. The simulation result demonstrated that calcium signal extruded from spine into dendrite requires amplification by CICR before invading neighboring spines to induce plasticity. Our model predicted that initial calcium concentration in SER may discriminate between different types of neuronal activity and induce completely different synaptic potentiation and depression.

Active fraction combination from Liuwei Dihuang decoction(LW-AFC) ameliorates corticosterone-induced long-term potentiation impairment in mice in vivo

Liuwei Dihuang decoction(LW), a classic formula in traditional Chinese medicine(TCM), has been used for nearly one thousand years for various diseases with characteristic features of kidney yin deficiency. LW consists of 6herbs including Dihuang[prepared root of Rehmannia glutinosa(Gaertn) DC], Shanyao(rhizome of Dioscorea polystachya Turcz), Shanzhuyu(fruit of Cornus officinalis Siebold Zucc), Mudanpi(root bark of Paeonia × suffruticosa Andrews),Zexie(rhizome of Alisma plantago-aquatica L) and Fuling(scleorotia of Wolfiporia extensa(Peck) Ginns)LW-active fraction combination(LW-AFC) is extracted from LW, it is effective for the treatment of kidney yin deficiency in many animal models. There are 3 fractions in LW-AFC, a polysaccharide fraction(LWB-B), a glycoside fraction(LWD-b) and an oligosaccharide fraction(CA-30). Our previous results indicate that LW-AFC has similar pharmacological effects to LW, modulating the balance of the NIM network. LW-AFC has positive effects in many animal models of kidney deficiency or disturbance of the NIM network. LW-AFC could improve the cognitive ability in Alzheimer′s disease(AD) animal models(APP/PS1, SAMP8), where modulating immune function and balancing the NIM network may play an important role in its cognition improving effects. Our study also showed that LW-AFC had protective effects on stress-induced disturbances of the NIM network. However, the underlying mechanisms remain elusive and need further investigation. OBJECTIVE This study evaluated the effects of LW-AFC and the active fractions(polysaccharide, LWB-B;glycoside, LWD-b;oligosaccharide,CA-30) on corticosterone(Cort)-induced long-term potentiation(LTP) impairment in vivo. METHODS LTP was used to evaluate the synaptic plasticity. LW-AFC was orally administered for seven days. The active fractions were given by either chronic administration(ig, ip, 7 d) or single administration(icv, ig, ip). Cort was injected subcutaneously 1 h before the high-frequency stimulation(HFS) to induce LTP impairment. Moreover, in order to research on the possible effective pathways, an antibiotic cocktail and an immunosuppressant were also used. RESULTS Chronic administration(ig) of LW-AFC and its three active fractions could ameliorate Cort-induced LTP impairment. Single administration(icv, ig, ip) of any of the active fractions had no effect on Cort-induced LTP impairment, while chronic administration(ig, ip) of LWB-B or LWD-b showed positive effects against Cort. Interestingly, CA-30 only showed protective effects via ig administration,and there was little effect when CA-30 was administered ip In addition, when the intestinal microbiota was disrupted by application of the antibiotic cocktail, CA-30 showed little protective effects against Cort. The effects of LW-AFC were also abolished when the immune function was inhibited. In the hippocampal tissue, Cort treatment increased corticosterone and glutamate, and LW-AFC could inhibit the Cort-induced elevation of corticosterone and glutamate;there was little change in D-serine in Cort-treated animals, but LW-AFC could increase the D-serine levels. CONCLUSION LW-AFC and its three active fractions could ameliorate Cort-induced LTP impairment. Their protective effects are unlikely by a direct way, and immune modulation might be the common pathway. CA-30 could protect LTP from impairment via modulating the intestinal microbiota. Decreasing corticosterone and glutamate and increasing D-serine in the Cort-treated animals’ hippocampal tissue might be one of the mechanisms for the neural protective effects of LW-AFC. Further study is needed to understand the underlying mechanisms.

Mechanisms of active fraction combination from Liuwei Dihuang Decoction(LW-AFC) on long-term potentiation impairment in vivo

OBJECTIVE Liuwei Dihuang Decoction(LW)-active fraction combination(LW-AFC,consist of 3 fractions polysaccharide,LWB-B;glycoside,LWD-b;oligosaccharide,CA-30)is extracted from LW,it is effective for the treatment of kidney yin deficiency in many animal models.This study evaluated the effects and mechanisms of LW-AFC and the active fractions on corticosterone(Cort)-induced long-term potentiation(LTP)impairment in vivo.METHODS LTP was used to evaluate the synaptic plasticity.LW-AFC was orally administered for seven days.The active fractions were given by either chronic administration(ig,ip,7 d)or single administration(icv,ig,ip).Cort was injected subcutaneously 1h before the high-frequency stimulation(HFS)to induce LTP impairment.Moreover,in order to research on the possible effective pathways,an antibiotic cocktail and an immunosuppressant were also used.RESULTS Chronic administration(ig)of LW-AFC and its three active fractions could ameliorate Cort-induced LTP impairment.Single administration(icv,ig,ip)of any of the active fractions had no effect on Cort-induced LTP impairment,while chronic administration(ig,ip)of LWB-B or LWD-b showed positive effects against Cort.Interestingly,CA-30 only showed protective effects via ig administration,and there was little effect when CA-30 was administered ip In addition,when the intestinal microbiota was disrupted by application of the antibiotic cocktail,CA-30 showed little protective effects against Cort.The effects of LW-AFC were also abolished when the immune function was inhibited.In the hippocampal tissue,Cort treatment increased Cort and glutamate,and LW-AFC could inhibit the Cort-induced elevation of Cort and glutamate;there was little change in D-serine in Cort-treated animals,but LW-AFC could increase the D-serine levels.CONCLUSION LW-AFC and its three active fractions could ameliorate Cort-induced LTP impairment.Their protective effects are unlikely by a direct way,and immune modulation might be the common pathway.CA-30 could protect LTP from impairment via modulating the intestinal microbiota.Decreasing Cort and glutamate and increasing D-serine in the Cort-treated animals'hippocampal tissue might be one of the mechanisms for the neural protective effects of LW-AFC.Further study is needed to understand the underlying mechanisms.

LW-AFC and its active components ameliorate corticosterone-induced long-term potentiation impairment in mice

OBJECTIVE LW-AFC is extracted from the classical traditional Chinese medicinal prescription-Liuwei Dihuang Decoction.Previous studies have showed that LW-AFC could improve learning&memory ability in amny animal models.In this study,we focused on evaluating the effect of several main active components fromLW-AFC(B-B;loganin,LOG;morroniside,MOR;paeoniflorin,PF and stachyose,STA)on LTP.METHODS In vivo recording of LTP was used in this study to evaluate the effects of LW-AFC and it′s active components on coticorsterone(Cort)induced LTP impairment.RESULTS The results showed that LW-AFC could ameliorate Cort-induced LTP impairment.The effect of LW-AFC was abolished when the immune function was inhibited.Single administration(ig,ip,icv)of any of the components had no effect on Cort-induced LTP impairment.Consecutively intragastric administration or intraperitoneal injections(chronic administration)of B-B,LOG,MOR or PF for 7 d showed protective effect on Cort-induced LTP impairment.Intragastric administration of STA for 7 d protected LTP from impairment induced by Cort,while there was little improving effect when STA was administrated via intraperitoneal injection.In addition,when the intestinal microbiota was disrupted by applying the antibiotic cocktail,STA showed little protective effect against Cort.CONCLUSION In conclusion,LW-AFC and it′s components showed positive effects against cort induced LTP impairment,it seems that all displayed protective effects via indirectly,immune modulation might be the common pathway for all components;the exact pathways are different in each component,B-B,LOG,MOR and PF could be absorbed into the bloods tream and then modulate the peripheral immune function,while STA could not be absorbed and modulates the immune function via modulating intestinal microbiota.Further studies are needed to invesgate the underlying mechanisms and the synergetic effects of all components.

Voltage-dependent plasticity and image Boolean operations realized in a WOx-based memristive synapse

The development of electronic devices that possess the functionality of biological synapses is a crucial step towards neuromorphic computing.In this work,we present a WOx-based memristive device that can emulate voltage-dependent synaptic plasticity.By adjusting the amplitude of the applied voltage,we were able to reproduce short-term plasticity(STP)and the transition from STP to long-term potentiation.The stimulation with high intensity induced long-term enhancement of conductance without any decay process,thus representing a permanent memory behavior.Moreover,the image Boolean operations(including intersection,subtraction,and union)were also demonstrated in the memristive synapse array based on the above voltage-dependent plasticity.The experimental achievements of this study provide a new insight into the successful mimicry of essential characteristics of synaptic behaviors.

Insulin Age-Dependently Modulates Synaptic Transmission and AMPA Receptor Trafficking in Region CA1 of the Rat Hippocampus

Insulin induces long-term depression (insulin-LTD) in the CA1 region of the rat juvenile hippocampus. This insulin-LTD may be due in part to internalization of the GluA2 subunit of the AMPA receptor (AMPAR) events that haven’t been studied in the mature rat hippocampus. In our studies, we used hippocampal preparations from juvenile (14 - 25 days) and mature (60 - 90 days) rats to assess insulin modulation of CA1 synaptic transmission and AMPAR trafficking and phosphorylation. Using field potential electrophysiology, we observed that insulin induced LTD in the juvenile hippocampus (as previously reported) in the presence and absence of phosphoinositide 3-kinase (PI3K) activity, but produced no significant long-term changes in the mature hippocampus in the presence of PI3K activity. Interestingly, during PI3K inhibition, insulin did produce LTD in the mature hippocampus. Additionally, insulin induced a long-term decrease in plasma membrane expression of the GluA2 and GluA1 subunits of the AMPAR in the juvenile, but not mature hippocampus. Furthermore, there was a long-term decrease in GluA1 phosphorylation at Serine 845 in the juvenile, but not mature hippocampus. These data reveal that insulin modulation of synaptic plasticity and AMPAR modulation within the hippocampus is age-dependent, suggesting that insulin-regulated behaviors may also show age-dependence. These findings are important largely due to the increased use of insulin as a therapeutic throughout the lifespan. Our data suggest that additional work should be done to determine how this use of insulin throughout different stages of life might affect synaptic function and development.

Targeting redox-altered plasticity to reactivate synaptic function: A novel therapeutic strategy for cognitive disorder

Redox-altered plasticity refers to redox-dependent reversible changes in synaptic plasticity via altering functions of key proteins, such as N-methyl-D-aspartate receptor(NMDAR). Age-related cognitive disorders includes Alzheimer’s disease(AD), vascular dementia(VD), and age-associated memory impairment(AAMI). Based on the critical role of NMDAR-dependent long-term potentiation(LTP) in memory, the increase of reactive oxygen species in cognitive disorders, and the sensitivity of NMDAR to the redox status, converging lines have suggested the redox-altered NMDAR-dependent plasticity might underlie the synaptic dysfunctions associated with cognitive disorders. In this review, we summarize the involvement of redox-altered plasticity in cognitive disorders by presenting the available evidence. According to reports from our laboratory and other groups, this "redox-altered plasticity" is Hydrogen sulfidemore similar to functional changes rather than organic injuries, and strategies targeting redox-altered plasticity using pharmacological agents might reverse synaptic dysfunctions and memory abnormalities in the early stage of cognitive disorders. Targeting redox modifications for NMDARs may serve as a novel therapeutic strategy for memory deficits.

Dopaminergic modulation of synaptic plasticity in rat prefrontal neurons

The prefrontal cortex （PFC） is thought to store the traces for a type of long-term memory - the memory that determines the temporal structure of behavior often termed a ＂rule＂ or ＂strategy＂. Long-term synaptic plasticity might serve as an underlying cellular mechanism for this type of memory. We therefore studied the induction of synaptic plasticity in rat PFC neurons, maintained in vitro, with special emphasis on the functionally important neuromodulator dopamine. First, the induction of long-term potentiation （LTP） was facilitated in the presence of tonic/background dopamine in the bath, and the dose-dependency of this background dopamine followed an ＂inverted-U＂ function, where too high or too low dopamine levels could not facilitate LTP. Second, the induction of long-term depression （LTD） by low-frequency stimuli appeared to be independent of background dopamine, but required endogenous, phasically-released dopamine during the stimuli. Blockade of dopamine receptors during the stimuli and exaggeration of the effect of this endogenouslyreleased dopamine by inhibition of dopamine transporter activity both blocked LTD. Thus, LTD induction also followed an inverted-U function in its dopamine-dependency. We conclude that PFC synaptic plasticity is powerfully modulated by dopamine through inverted-U-shaped dose-dependency.

新型抗癫痫药Q808对颞叶癫痫大鼠的改善作用及其机制

目的:探讨新型抗癫痫药6-(4-氯苯氧基)-四唑^((5,1-a))酞嗪(Q808)对颞叶癫痫(TLE)大鼠神经元损伤的改善作用,并阐明其作用机制。方法:采用腹腔注射Q808的方法制备TLE大鼠模型。将45只造模成功大鼠随机分为模型组、低剂量Q808组和高剂量Q808组,每组15只,低剂量Q808组和高剂量Q808组大鼠分别采用20和80 mg·kg^(-1) Q808灌胃,模型组大鼠采用等量0.3%羧甲纤维素钠灌胃,另选15只健康SD大鼠作为对照组。持续灌胃治疗4周后,观察各组大鼠行为表现,采用PONEMAH 6. X实验动物遥测平台记录各组大鼠脑电图,采用高尔基染色观察各组大鼠海马CA1神经元树突形态表现和神经元树突棘密度,采用Western blotting法检测各组大鼠海马组织中突触可塑性特异性蛋白钙/钙调素依赖性蛋白激酶Ⅱ(CaMKⅡ)蛋白表达水平。结果:对照组大鼠活动正常,无抽搐等异常表现;模型组、低剂量Q808和高剂量Q808组大鼠出现不同程度活动减少、震颤点头、失去平衡、肌肉强直和前肢的抽搐,逐渐转变为全身肌肉强直和站立,随后向后跌倒,发作间期无抽搐发作。与对照组比较,模型组、低剂量Q808和高剂量Q808组大鼠癫痫发作总持续时间明显延长(P<0.01);与模型组比较,低剂量Q808和高剂量Q808组大鼠癫痫发作总持续时间明显缩短(P<0.01)。对照组大鼠海马组织CA1区神经元树突分布较为规律,树突网密集有序;模型组大鼠海马组织CA1区神经元树突排列紊乱,大量树突缠结,形成较粗大的神经纤维束;与模型组比较,低剂量Q808和高剂量Q808组大鼠海马组织CA1区神经元树突网络有所恢复,排列相对规律。与对照组比较,模型组大鼠海马组织CA1区神经元树突棘密度明显降低(P<0.01);与模型组比较,低剂量Q808和高剂量Q808组大鼠海马组织CA1区神经元树突棘密度明显升高(P<0.01)。与对照组比较,模型组、低剂量Q808组和高剂量Q808组大鼠海马组织中CaMKⅡ蛋白表达水平明显降低(P<0.01);与模型组比较,低剂量Q808组和高剂量Q808组大鼠海马组织中CaMKⅡ蛋白表达水平明显升高(P<0.01)。结论:新型抗癫痫药Q808对TLE模型大鼠有改善作用,其机制可能与Q808能减轻海马组织CA1区神经元树突病变和增加突触可塑性相关蛋白CaMKⅡ蛋白表达水平有关。

三七总皂苷对海马CA1区长时程增强效应的影响

三七总皂苷（Panaxnotoginsengsaponins,PNS）是从传统中药三七的根中提取的主要有效成分,具有改善血液循环、耐缺氧、改善记忆力、抗衰老等多方面的生理活性。本研究采用“盲法”全细胞膜片钳技术观察PNS对大鼠海马CA1区锥体神经元长时程增强效应（LTP）的影响,以分析其增强学习记忆功能的神经电生理机制。以断头法分离Wistar大鼠（3-4周）海马半脑,用切片机切出400μm厚度的海马脑片,以全细胞电压钳制方式记录CA1区锥体细胞的兴奋性突触后电流（EPSCs）,给予高频刺激HFS（100 Hz）诱导LTP,分析PNS对大鼠海马CA1区EPSCs和LTP的影响。结果表明,PNS（0.1-0.4 g·L^-1）能显著抑制EPSCs（P〈0.05）,且对海马CA1区LTP无易化作用;但PNS（0.04-0.05 g·L^-1）不影响CA1区的EPSCs基础突触传递（P〉0.05）,却可以增强HFS诱发的LTP（P〈0.05）。上述结果提示,PNS（0.04-0.05 g·L^-1）能易化海马CA1区锥体神经元的长时程增强效应,该作用应是其增进学习记忆力的神经电生理机制。

皮质酮对大鼠海马颗粒细胞层长时程增强效应的抑制作用(英文)

通过胞外记录大鼠海马颗粒细胞层诱发电位观察了皮质酮对麻醉大鼠海马神经突触可塑性的影响． 结果显示，皮质酮（１， ４ 和１０ ｍ ｇ·ｋｇ－ １， ｉｐ）有使单刺激大鼠海马颗粒细胞层基础群峰电位（ＰＳ）幅度升高的趋势，但同对照相比无显著性差异． 给予大鼠穿行通路以串刺激（６０ Ｈｚ， ３０ 次）可使海马颗粒细胞层ＰＳ幅度持续增高，增幅达７０％ － ８０％ ，说明在海马诱生长时程增强效应（ＬＴＰ）． 预先１ ｈ给予大鼠皮质酮（１， ４ 和１０ ｍ ｇ·ｋｇ－ １， ｉｐ）可剂量依赖地降低串刺激诱导的ＰＳ幅度的升高，说明皮质酮可抑制海马颗粒细胞层ＬＴＰ的诱生． 结果提示，皮质酮可损伤大鼠海马神经突触可塑性．

开心散影响突触可塑性的研究进展

本文综述了中药复方开心散对突触可塑性、长时程增强效应的影响,表明了开心散能够促进突触的长时程增强的形成与巩固,对抗某些物质对长时程增强的抑制作用,显示了良好的促进记忆和学习的作用。

学习和记忆的突触模型:长时程突触可塑性

人类大脑是由上千亿神经元相互连接而组成一个高度复杂的神经网络,是认知、学习和意识等高级功能的重要基础。神经元之间通过特化的连接结构——"突触"而相互通讯。外界输入触发的神经元活动可特异性地持续改变突触的结构和功能,这种神经活动依赖的突触变化称之为长时程突触可塑性。大量实验证据表明突触可塑性是大脑学习和记忆的分子细胞学机制,了解突触可塑性的机制对阐明中枢神经系统性相关疾病(如老年痴呆症、药物成瘾等)的机理具有重要意义。本文简要地小结了长时程突触可塑性研究中的基本发现和新近进展。