The mechanisms underlying long-term potentiation of C-fiber evoked field potentials in spinal dorsal horn

Long-term potentiation(LTP) of C-fiber evoked field potentials in spinal dorsal horn is first reported in 1995.Since then,the mechanisms underlying the long-lasting enhancement in synaptic transmission between primary afferent C-fibers and neurons in spinal dorsal horn have been investigated by different laboratories.In this article,the related data were summarized and discussed.

Electric stimulation at sciatic nerve evokes long-term potentiation of cornu dorsale medullae spinalis field potential in rats at various developmental phases

BACKGROUND： Long-term potentiation of cornu dorsale medullae spinalis field potential in adult rats has already been reported; however, there is lack of correlated researches on naenonate, infant and adult rats which have different responses to pain conduction information.OBJECTIVE： To observe the various effects of electric stimulation at sciatic nerve on long-term potentiation of evoked field potential at superficial layer of cornu dorsale medullae spinalis of rats at various developmental phases and analyze manifestations of pain conduction information at superficial layers （ Ⅰ - Ⅱ）of cornu dorsale medullae spinalis in immature rats.DESIGN： Grouping controlled study.SETTING： Department of Physiology, Medical College of Wuhan University.MATERIALS： The experiment was carried out in the Laboratory of Physiology （provincial laboratory）,Medical College of Wuhan University from March 2006 to May 2007. A total of 27 healthy male Sprague-Dawley （SD） rats, 17- 90 days old, SPF grade, weighing 41 -200 g, were provided by Experimental Animal Center, Medical College of Wuhan University.METHODS： Based on their birthdays, rats were divided into naenonate group （17 - 20 days old, weighing 41-52 g, n =10）, infant group （35 - 50 days old, weighing 87 - 125 g, n =10） and adult group （60 - 90 days old, weighing 180 -200 g, n =7）. Left sciatic nerve was separated and stimulated with single square wave （15 V, 0.5 ms）. Meanwhile, evoked field potential was recorded at superficial layers of lateral T13 - L1 cornu dorsale medullae spinalis and then stimulated with high-frequent and high-intensive tetanizing current （30 -40 V, 0.5 ms, 100 Hz, 1s per bundle, 10s in bundle interval） four times. After the operation, onset of long-term potentiation was observed; meanwhile, amplitude changes and latency of field potential were analyzed.MAIN OUTCOME MEASURES： Amplitude and latency changes of field potential at superficial layers of cornu dorsale medullae spinalis of rats in the three groups.RESULTS： A total of 27 accepted rats were involved in the final analysis. ① Amplitude changes： Electric stimulation at sciatic nerve with high-frequent and high-intensive tetanizing current could induce evoked field potential at superficial layers （Ⅰ-Ⅱ ） of cornu dorsale medullae spinalis in the three groups.Long-term potentiation in the naenonate group manifested that amplitude of A-kind never fiber was raised and there was significant difference （P〈0.05）. In addition, average amplitude was increased and there was obviously significant difference （P〈0.01）. Long-term potentiation in the infant group manifested that amplitude of C-kind never fiber was raised and there was significant difference （P〈0.01）; while, long-term potentiation in the adult group manifested that amplitude of C-kind never fiber was raised and there was significant difference （P〈0.01）. Otherwise, latencies in the three groups were all shortened. ② Latency changes： Average latency of A-kind nerve fiber in the naenonate group was shortened and there was significant difference （P〈0.01）; in addition, evoked potential of C-kind nerve fiber was low and latency was immovable. There was no significant difference before and after high-frequent and high-intensive electric stimulation （P〉0.05）. Average latency of C-kind nerve fiber in the infant group was shortened and there was significant difference （P〈0.01）; in addition, evoked potential of A-kind nerve fiber was stable and latency was immovable. There was no significant difference before and after high-frequent and high-intensive electric stimulation （P〉0.05）. Average latency of C-kind nerve fiber in the adult group was shortened and there was significant difference （P〈0.01）; in addition, evoked potential of A-kind nerve fiber was stable and latency was immovable. There was no significant difference before and after high-frequent and high-intensive electric stimulation.CONCLUSION： Evoked field potential at superficial layer of comu dorsale medullae spinalis can be recorded through electric stimulation at sciatic nerve. Single stimulation and tetanizing electric stimulation can cause different characteristics of evoked field potential in rats at various developmental phases.Superficial layer of cornu dorsale medullae spinalis of naenonate rats is mainly caused by A-kind nerve fiber which participants in pain conduction and formation of pain sensitivity; however, that of infant and adult rats mainly depends on C-kind nerve fiber.

Potential Legal Issues and Care Implications during Care-Prevention Gymnastic Exercises for the Elderly Using Pepper in Long Term Health Care Facilities

In Japan, the shortage of personnel is a problem in long-term care nursing and rehabilitative care prevention. Nevertheless, Japan has taken measures to compensate for these shortages by promoting medical and nursing care activities using robotic technologies, and employing human resources from overseas. The purpose of this study was to determine potential legal issues and subsequent implications for care during prevention gymnastic exercises for the elderly using Pepper in long-term health facilities. The application program of Care-Prevention Gymnastics Exercises for Pepper (Pepper with CPGE) was made by the Xing Company Japan. Currently, care workers become intermediaries for the safe use of Pepper with CPGE. However, it was realized that some legal issues may arise if Pepper with CPGE alone will carry out these preventive care programs for the elderly without the presence of care workers as intermediaries. In this situation, using Pepper with CPGE alone to conduct care prevention gymnastics will require safety measures to prevent these possible practice issues and anticipate implications for care. In this regard, determining detailed target levels of rehabilitation exercise demands and environmental setting safety become essential factors. The use of humanoid robots in healthcare is expected to influence more practice protocols in contemporary and futurist rehabilitative human care. The identification of possible safety issues in performance and environmental situations, and implications for care are critical to ensure safe and valuable rehabilitative health care practices for the elderly population.

Effects of Exposure to Aluminum on Long-term Potentiation and AMPA Receptor Subunits in Rats in vivo

Objective To explore the effects of exposure to aluminum （AI） on long-term potentiation （LTP） and AMPA receptor subunits in rats in vivo. Methods Different dosages of aluminum-maltolate complex [Al（mal）3] were given to rats via acute intracerebroventricular （i.c.v.） injection and subchronic intraperitoneal （i.p.） injection. Following AI exposure, the hippocampal LTP were recorded by field potentiation technique in vivo and the expression of AMPAR subunit proteins （GluR1 and GluR2） in both total and membrane-enriched extracts from the CA1 area of rat hippocampus were detected by Western blot assay. Results Acute AI treatment produced dose-dependent suppression of LTP in the rat hippocampus and dose-dependent decreases of GluRz and GluR2 in membrane extracts; however, no similar changes were found in the total cell extracts, which suggests decreased trafficking of AMPA receptor subunits from intracellular pools to synaptic sites in the hippocampus. The dose-dependent suppressive effects on LTP and the expression of AMPA receptor subunits both in the membrane and in total extracts were found after subchronic AI treatment, indicating a decrease in AMPA receptor subunit trafficking from intracellular pools to synaptic sites and an additional reduction in the expression of the subunits. Conclusion Al（mal）3 obviously and dose-dependently suppressed LTP in the rat hippocampal CA1 region in vivo, and this suppression may be related to both trafficking and decreases in the expression of AMPA receptor subunit proteins. However, the mechanisms underlying these observations need further investigation.

The RAS/PI3K Pathway is Involved in the Impairment of Long-term Potentiation Induced by Acute Aluminum Treatment in Rats

Objective To explore the role of RAS/PI3K pathway in the impairment of long-term potentiation （LTP） induced by acute aluminum （AI） treatment in rats in vivo. Methods First, different dosages of aluminum-maltolate complex [Al（mal）3] were given to rats via acute intracerebroventricular （i.c.v.） injection. Following AI exposure, the RAS activity of rat hippocampus were detected by ELISA assay after the hippocampal LTP recording by field potentiation technique in vivo. Second, the antagonism on the aluminum-induced suppression of hippocampal LTP was observed after the treatment of the RAS activator epidermal growth factor （EGF）. Finally, the antagonism on the downstream molecules （PKB activity and the phosphorylation of GluR1 $831 and $845） were tested by ELISA and West-blot assays at the same time. Results With the increasing aluminum dosage, a gradually decreasing in RAS activity of the rat hippocampus was produced after a gradually suppressing on LTP. The aluminum-induced early suppression of hippocampal LTP was antagonized by the RAS activator epidermal growth factor （EGF）. And the EGF treatment produced changes similar to those observed for LTP between the groups on PKB activity as well as the phosphorylation of GluR1 S831 and s845. Conclusion The RAS-PI3K/PKB-GluR1 S831 and S845 signal transduction pathway may be involved in the inhibition of hippocampal LTP by aluminum exposure in rats. However, the mechanisms underlying this observation need further investigation.

Effects of Chronic Administration of Melatonin on Spatial Learning Ability and Long-term Potentiation in Lead-exposed and Control Rats

Objective To explore the changes in spatial learning performance and long-term potentiation （LTP） which is recognized as a component of the cellular basis of learning and memory in normal and lead-exposed rats after administration of melatonin （MT） for two months. Methods Experiment was performed in adult male Wistar rats （12 controls, 12 exposed to melatonin treatment, 10 exposed to lead and 10 exposed to lead and melatonin treatment）. The lead-exposed rats received 0.2% lead acetate solution from their birth day while the control rats drank tap water. Melatonin （3 mg/kg） or vehicle was administered to the control and lead-exposed rats from the time of their weaning by gastric gavage each day for 60 days, depending on their groups. At the age of 81-90 days, all the animals were subjected to Morris water maze test and then used for extracellular recording of LTP in the dentate gyrus （DG） area of the hippocampus in vivo. Results Low dose of melatonin given from weaning for two months impaired LTP in the DG area of hippocampus and induced learning and memory deficit in the control rats. When melatonin was administered over a prolonged period to the lead-exposed rats, it exacerbated LTP impairment, learning and memory deficit induced by lead. Conclusion Melatonin is not suitable for normal and lead-exposed children.

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.

Study on Long-term Potentiation in Developing Rat Visual Cortex during the Critical Period of Plasticity

Purpose: To study the property of LTP in layers Ⅱ～Ⅳof the rats visual cortex at different postnatal days induced by pairing low-frequency stimulation at layer Ⅳ with post synaptic depolarization in order to explore the synaptic and cellular mechanism of experience-dependent plasticity in the visual cortex.Methods: Postsynaptic currents (PSCs) of layers Ⅱ～Ⅳ in visual cortex slices of Wistar rats aged P0-29 d were recorded by patch-clamp whole cell recording method. Long-term potentiation (LTP) was induced by low-frequency stimulation (LFS) at 1Hz for 60～90 s.Each pulse of the LFS paired with depolarization of post-synaptic neurons to -20 mV.100μM APV, a kind of competitive N-methyl-d-aspartate (NMDA) receptor antagonist, was both applied to some slices to test the property of LTP.Results: 1. The LTP incidence was very low before P10d (5/34), and increased rapidly to the top at P15-24 d (17/28), then decreased sharply to 1/5 at P25-29 d, coinciding well with the critical period of plasticity of rat visual cortex. The LTP incidence of P15-29d (after eye opening, 18/33) was significantly higher than that of P0-14 d (before eye opening, 12/43, P ＜ 0.05). 2. Compared with non-APV applied group (30/76), LTP incidence of APV applied group (4/33) was significantly decreased (P ＜ 0.01 ). There were 4 Ⅳ-Ⅳ horizontal synapses. APV application could not block the LTP induction.Conclusions: 1. LTP was a reflection of naturally occurring, experience-dependent plasticity in rat visual cortex. The patterned visual stimuli received after eye opening might be an activation factor of the synaptic plasticity. 2. LTP of visual cortex induced by LFS in layer Ⅳ paired with postsynaptic depolarization was NMDA receptor dependent during the critical period of visual plasticity. However, there were LTP existed in Ⅳ-Ⅳ horizontal synapses which could not be blocked by 100μM APV.

Effect of Aluminum on Long-Term Potentiation and Its Relation to L-arg-No-pathway in Hippocampal CA3 Area of Rats

Experiments were performed on 64 Sprague-Dawley rats under ure-thane anesthesia. Extracellular recording method was used to investigate the effect of aluminum (Al)microinjected into CA3 on long-term potentiation (LTP) in this area. The relationship between the inhibitory effect of Al and L-arginine-NO pathway was also studied. Microinjection of Al (0. 5 mol/L, 1 μl ) into CA3 could block the induction of LTP in CA3. Microinjection of Al (0. 5 mol/L, 1 μl) into CA3 after LTP was induced could also decrease the amplitude of population spike (PS). The inhibitory effect of Al on LTP in CA3 could be enhanced by preinjection of NG-nitro-L-arginine (0. 3 mol/L, 1 μl). Preinjection of L-arginine (0. 3 mol/L, 1 μl) into CA3 could antagonize the inhibitory effect of Al on LTP. These results suggest that Al could block the induction of LTP and decrease the amplitude of PS potentiated in CA3. The effect of Al might be antagonized by L-arginine-NO pathway.

Correlating learning and memory improvements to long-term potentiation in patients with brain injury

BACKGROUND： Brain injury patients often exhibit learning and memory functional deficits. Long-term potentiation （LTP） is a representative index for studying learning and memory cellular models; the LTP index correlates to neural plasticity. OBJECTIVE： This study was designed to investigate correlations of learning and memory functions to LTP in brain injury patients, and to summarize the research advancements in mechanisms underlying brain functional improvements after rehabilitation intervention. RETRIEVAL STRATEGY： Using the terms ＂brain injuries, rehabilitation, learning and memory, long-term potentiation＂, manuscripts that were published from 2000-2007 were retrieved from the PubMed database. At the same time, manuscripts published from 2000-2007 were also retrieved from the Database of Chinese Scientific and Technical Periodicals with the same terms in the Chinese language. A total of 64 manuscripts were obtained and primarily screened. Inclusion criteria： studies on learning and memory, as well as LTP in brain injury patients, and studies focused on the effects of rehabilitation intervention on the two indices; studies that were recently published or in high-impact journals. Exclusion criteria： repetitive studies. LITERATURE EVALUATION： The included manuscripts primarily focused on correlations between learning and memory and LTP, the effects of brain injury on learning and memory, as well as LTP, and the effects of rehabilitation intervention on learning and memory after brain injury. The included 39 manuscripts were clinical, basic experimental, or review studies. DATA SYNTHESIS： Learning and memory closely correlates to LTP. The neurobiological basis of learning and memory is central nervous system plasticity, which involves neural networks, neural circuits, and synaptic connections, in particular, synaptic plasticity. LTP is considered to be an ideal model for studying synaptic plasticity, and it is also a classic model for studying neural plasticity of learning and memory. Brain injury patients clinically present with various manifestations, such as paralysis and sensory disability, which closely correlate to injured regions. In addition, learning and memory abilities decrease in brain injury patients and LTP decreases following brain injury. Brain tissue injury will lead to brain functional deficits. Hippocampal LTP is very sensitive. Difficulties in LTP induction are apparent even prior to morphological changes in brain tissue. There are no specific treatments for learning and memory functional deficits following brain injury. At present, behavioral and compensative therapies are the typical forms of rehabilitation. These results indicate that rehabilitation promotes learning and memory functional recovery in brain injury patients by speeding up LTP formation in the hippocampal CA3 region. CONCLUSION： Rehabilitation intervention increases LTP formation in the hippocampal CA3 region and recovers learning and memory functions in brain injury patients.

Effects of electroacupuncture versus nimodipine on long-term potentiation and synaptophysin expression in a rat model of vascular dementia

The present study stimulated Baihui （DU 20） and Dazhui （DU 14） acupoints in a rat model of vascular dementia with electroacupuncture to investigate changes in long-term potentiation and synaptophysin expression in the hippocampus. The results revealed that synaptophysin expression in brain tissues was increased after electroacupuncture. After high4requency stimulation, the population spike latency was shortened and the excitatory postsynaptic potential slope and population spike amplitude were increased. In addition, cognitive function was enhanced, similar to the effects of intragastric perfusion of nimodipine. The results indicated that electroacupuncture at Baihui and Dazhui acupoints can improve learning and memory functions of a rat model of vascular dementia by promoting synaptophysin expression, enhancing hippocampal synaptic plasticity and accelerating synaptic transmission.

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.

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.

褪黑素改善D-半乳糖诱导的小鼠认知功能障碍

目的探讨褪黑素对D-半乳糖诱导的小鼠认知功能障碍的改善作用及潜在机制。方法将8周龄雄性C57BL/6小鼠随机分为3组:对照组(Control组)、D-半乳糖组(D-gal组)和D-半乳糖+褪黑素组(D-gal+MLT组),D-半乳糖采取腹腔注射(100 mg/kg),褪黑素采取灌胃(10 mg/kg),1次/d,持续3个月。采取Morris水迷宫实验评价小鼠认知功能;场电位长时程增强(long-term potentiation,LTP)实验评估药物对小鼠突触可塑性的影响;采用Western blots法测定小鼠海马和皮层组织中突触后致密蛋白(postsynaptic density-95,PSD95)、突触生长蛋白(synaptophysin,SYN)、沉默信息调节因子(sirtuin 1,SIRT1)及脑源性神经营养因子(brain-derived neurotrophic factor,BDNF)的蛋白表达水平。结果与对照组相比,D-gal组小鼠水迷宫实验逃避潜伏期延长,目标象限停留时间明显减少(均P<0.05),LTP受损(P<0.01),海马和皮层组织中PSD95、SYN、BDNF的蛋白表达显著降低(均P<0.05)。与D-gal组比较,褪黑素干预后(D-gal+MLT组)小鼠水迷宫实验逃避潜伏期显著缩短(P<0.05),LTP受损明显改善(P<0.01),海马和皮层组织中PSD95、SYN、SIRT1及BDNF蛋白表达水平显著增加(均P<0.05)。结论褪黑素对D-半乳糖诱导小鼠的认知功能障碍具有改善作用,其作用机制可能是通过提高SIRT1-BDNF表达水平,进而提高小鼠海马CA1区LTP,改善小鼠突触可塑性。

基于APF-LSTM-DDPG算法的移动机器人局部路径规划

针对深度强化学习算法存在训练时间长、收敛速度慢的问题,将深度确定性策略梯度(deep deterministic policy gradient,DDPG)算法和人工势场(artifical potential field,APF)法相融合,引入长短期记忆(long short-term memory,LSTM)神经网络结构,提出了APF-LSTM-DDPG算法。首先在DDPG算法中添加LSTM,通过记忆单元和遗忘单元将奖励较高的样本优先学习,使模型更快地收敛;其次引入人工势场法,设计相应势场函数,解决环境奖励稀疏的缺点,加速模型收敛进程;然后通过人工势场法修正算法的动作选择,缩短路径长度;最后在机器人仿真平台(robot operating system,ROS)中搭建不同障碍物环境对算法进行了仿真验证。仿真结果表明,APF-LSTM-DDPG算法在搭建的仿真环境中训练时平均奖励能够更快地稳定,提高了算法的成功率并减少了规划路径中的冗余。

Effects of long-term sustained naltrexone release on the optic center in opioid-dependent patients Case-control study in four provinces of China

Very little is known about visual functional recovery following long-term naltrexone administration in opioid-dependent patients. In the present study, a portable event-related potential （ERP） working system was utilized to collect and record ERP in opioid-dependent patients and normal controls in visual half-field testing. In addition, the influence of long-term sustained naltrexone release on the visual nervous system was observed in opioid-dependent patients. Results revealed a significant main group effect in reaction time to visual signal stimulations. The reaction time of normal controls was shortest, but longest in opioid-dependent patients. The reaction time of long-term sustained naltrexone release group and compulsory detoxification group was similar to normal controls. A significant main group effect was also observed in P100 latency, and P100 latency in normal controls and the compulsory detoxification group was significantly decreased compared with the opioid-dependent patients. P100 amplitude at the Oz-electrode resulted in a significant main group effect. In particular, normal controls exhibited significant differences compared with long-term sustained release naltrexone and compulsory detoxification groups. These findings demonstrated that long-term sustained naltrexone release effectively ameliorated optic center function and improved visual sensitivity and reactions in opioid-dependent patients.

Hippocampal ischemia causes deficits in local field potential and synaptic plasticity

The long-term enhancement in glutamate receptor mediated excitatory responses has been observed in stroke model. This pathological form of plasticity, termed post-ischemic long-term potentiation （i-LTP）, points to functional reorganization after stroke. Little is known, however, about whether and how this i-LTP would affect subsequent induction of synaptic plasticity. Here, we first directly confirmed that i-LTP was induced in the endothelin-l-induced ischemia model as in other in vitro models. We also demonstrated increased expression of NR2B, CaMKII and p-CaMKII, which are reminiscent of i-LTP. We further induced LTP of field excitatory post- synaptic potentials （fEPSPs） on CA1 hippocampal neurons in peri-infarct regions of the endothelin-l-induced mini-stroke model. We found that LTP of fEPSPs, induced by high-frequency stimulation, displayed a progressive impairment at 12 and 24 hours after ischemia. Moreover, using in vivo multi-channel recording, we found that the local field potential, which represents electrical property of cell ensembles in more restricted regions, was also dam- pened at these two time points. These results suggest that i-LTP elevates the induction threshold of subsequent synap- tic plasticity. Our data helps to deepen the knowledge of meta-synaptic regulation of plasticity after focal ischemia.

运动疲劳损害大鼠空间认知能力并导致海马CA1区L-LTP抑制

目的:探讨运动疲劳对空间认知能力的影响及海马突触可塑性调控机制。方法:采用随机数字法将雄性SD大鼠分为对照组(control)和疲劳组(fatigue),选用3级递增负荷跑台训练方案,建立慢性力竭运动疲劳模型。利用Y迷宫空间识别记忆实验评估大鼠的空间识别和记忆变化,使用Western Blot测定海马组织cAMP反应元件结合蛋白(CREB)表达及磷酸化水平,并利用在体电生理记录大鼠海马CA1区晚期时相长时程增强效应(L-LTP),随后通过免疫组织化学染色观察大鼠海马CA1区小清蛋白(PV)的表达。结果:疲劳组大鼠在新异臂的停留时间比和在各臂的总穿梭次数均明显低于对照组(P<0.01)。高频刺激后30、60、120直至180 min,疲劳组大鼠海马CA1区场兴奋性突触后电位(fEPSP)斜率较对照组大鼠均显著降低(P<0.01)。Western Blot结果表明,疲劳组大鼠海马组织磷酸化CREB(p-CREB)水平明显低于对照组(P<0.05)。免疫组织化学染色显示,疲劳组大鼠海马CA1区PV表达下调(P<0.05)。结论:运动疲劳可导致大鼠空间认知能力受损,其机制可能与海马L-LTP抑制、CREB磷酸化水平降低以及PV阳性神经元减少有关。

基于MF-LSTM的城市电动汽车集中充电负荷可调潜力评估

在新型电力系统背景下,电网需求侧可调控资源对于系统稳定的重要性日益提升。电动汽车作为重要的可调度负荷资源,对其可调度潜力进行准确评估,能有效提升电网安全稳定运行能力。现有研究较少考虑电动汽车用户行为偏好对电网负荷调控的影响,因此,提出一种考虑用户充电偏好的电动汽车集中式电站可调潜力评估方法。考虑电动汽车充电时的外部条件与自身行为偏好因素,建立基于隶属度函数的用户充电行为模型,并结合长短期记忆神经网络算法对充电站的可调潜力进行评估。最后,通过实际充电站算例,分析了电动汽车用户与负荷可调度潜力之间的耦合关系,验证了所提方法对负荷可调控容量评估的有效性,为电动汽车可调负荷参与削峰填谷等需求响应服务提供了理论支撑。

Ghrelin基因敲除对小鼠黑质区多巴胺能神经元突触后电位的影响

目的探讨胃饥饿素(ghrelin)基因敲除对小鼠黑质多巴胺能神经元突触后电位的影响。方法分别选取10周龄雄性ghrelin基因敲除小鼠(ghrelin^(-/-)组)及其同窝雄性野生型(WT)小鼠(WT组)的黑质组织,采用转录组学测序(RNA-seq)技术筛选差异表达基因(DEGs),通过KEGG通路富集分析DEGs可能参与的神经元突触活动相关信号通路,采用实时荧光定量PCR(RT-qPCR)方法对筛选出的DEGs进行验证,并应用蛋白免疫印迹(Western blotting)方法检测神经元突触活动相关基因的蛋白表达情况。结果与WT组相比,ghrelin^(-/-)组小鼠多巴胺能神经元突触传递信号通路上的23个基因水平发生了显著性变化,其中谷氨酸促离子型受体α-氨基-3-羟基-5-甲基-4-异唑丙酸型亚基3(GluA3)和糖原合酶激酶-3β(GSK-3β)分别调控神经元突触后膜上的α-氨基-3-羟基-5-甲基-4-异唑丙酸受体和N-甲基-D-天冬氨酸受体;在ghrelin^(-/-)组小鼠黑质组织中,GluA 3和GSK-3β基因表达出现明显的下调。RT-qPCR方法检测结果显示,与WT组相比,ghrelin^(-/-)组小鼠黑质组织当中GluA 3和GSK-3βmRNA水平明显下调(t=2.408、2.740,P<0.05)。Western blotting方法检测结果显示,与WT组相比,ghrelin^(-/-)组小鼠黑质组织中GluA3蛋白的表达水平明显上调(t=2.530,P<0.05),GSK-3β蛋白的表达明显下调(t=3.469,P<0.05)。结论Ghrelin基因敲除可能通过使小鼠黑质多巴胺能神经元突触后电位长时程增强,从而增强兴奋性突触传递活动,参与运动调控。