Gamma神经振荡产生机制及其功能研究进展

Gamma神经振荡的频率在30～100 Hz之间,存在于动物和人类大脑的多个区域,如丘脑、体感皮层以及海马等部位,在各个尺度水平上都可被检测到.抑制性中间神经元组成的神经网络是产生此高频节律性活动的主要条件之一.皮层的gamma神经振荡与丘脑-皮层系统有关.Gamma神经振荡具有易化突触可塑性和调节神经网络的作用,主要参与感觉特征绑定、选择性注意以及记忆等高级功能.     

Traffic of botulinum toxins A and E in excitatory and inhibitory neurons

Botulinum neurotoxins (BoNTs), proteases specific for the SNARE proteins, are used to study the molecular machinery supporting exocytosis and are used to treat human diseases characterized by cholinergic hyperactivity. The recent extension of the use of BoNTs to central nervous system (CNS) pathologies prompted the study of their traffic in central neurons. We used fluorescent BoNT/A and BoNT/E to study the penetration, the translocation and the catalytic action of these toxins in excitatory and inhibitory neurons. We show that BoNT/A and BoNT/E, besides preferentially inhibiting synaptic vesicle recycling at glutamatergic relative to Gamma-aminobutyric acid (GABA)-ergic neurons, are more efficient in impairing the release of excitatory than inhibitory neurotransmitter from brain synaptosomes. This differential effect does not result from a defective penetration of the toxin in line with the presence of the BoNT/A receptor, synaptic vesicle protein 2 (SV2), in both types of neurons. Interestingly, exogenous expression of SNAP-25 in GABAergic neurons confers sensitivity to BoNT/A. These results indicate that the expression of the toxin substrate, and not the toxin penetration, most likely accounts for the distinct effects of the two neurotoxins at the two types of terminals and support the use of BoNTs for the therapy of CNS diseases caused by the altered activity of selected neuronal populations.     

Influence of glutamate and GABA transport on brain excitatory/inhibitory balance

An optimally functional brain requires both excitatory and inhibitory inputs that are regulated and balanced. A perturbation in the excitatory/inhibitory balance—as is the case in some neurological disorders/diseases (e.g. traumatic brain injury Alzheimer’s disease, stroke, epilepsy and substance abuse) and disorders of development (e.g. schizophrenia, Rhett syndrome and autism spectrum disorder)—leads to dysfunctional signaling, which can result in impaired cognitive and motor function, if not frank neuronal injury. At the cellular level, transmission of glutamate and GABA, the principle excitatory and inhibitory neurotransmitters in the central nervous system control excitatory/inhibitory balance. Herein, we review the synthesis, release, and signaling of GABA and glutamate followed by a focused discussion on the importance of their transport systems to the maintenance of excitatory/inhibitory balance.     

Dynamics of networks of randomly connected excitatory and inhibitory spiking neurons

Recent advances in the understanding of the dynamics of populations of spiking neurones are reviewed. These studies shed light on how a population of neurones can follow arbitrary variations in input stimuli, how the dynamics of the population depends on the type of noise, and how recurrent connections influence the dynamics. The importance of inhibitory feedback for the generation of irregularity in single cell behaviour is emphasized. Examples of computation that recurrent networks with excitatory and inhibitory cells can perform are then discussed. Maintenance of a network state as an attractor of the system is discussed as a model for working memory function, in both object and spatial modalities. These models can be used to interpret and make predictions about electrophysiological data in the awake monkey.     

非洲爪蟾顶盖神经元的抑制性微突触后电流频率和振幅的电压依赖性

采用全细胞记录膜片钳技术,研究非洲爪蟾脑片视顶盖神经元微突触后电流（miniature inhibitory postsynaptic current,mIPSC）频率和振幅对电压依赖关系。观察到以下结果：（1）当通过改变记录电极内的DC电流,将神经元的膜电位从静息电位逐步（每步10mV的增量）去极化或超极化时,mIPSC的频率和,或振幅分别升高或降低。随着膜电位的去极化,mIPSC的频率逐渐升高;当钳位电压升至＋10mV时,mIPSC的频率达到最高值。（2）当神经元去极化时,振幅仅轻微升高。膜电位去极化达到-30mV或-40mV时,mIPSC的振幅最大：进一步去极化,振幅反而下降。另外,在膜电位去极化至-20mV和＋10mV之间时,可记录到大的mIPSC。（3）在无Ca^2＋浸浴液中,mIPSC的频率和振幅也随膜电位的去极化而逐步增高,但频率的增高幅度远不如在生理盐水浸浴中增高幅度明显。（4）当浸浴液中[K＋]0增高时,mIPSC的频率明显降低,而振幅轻微降低。当细胞外[K^＋]。浓度升高超过20mmol／L时,神经元产生明显的缓慢内向或外向膜电流。mIPSC频率和振幅与膜电位存在依赖性的可能机制在文中作了简短的讨论。     

Modulatory effects of Gs-coupled excitatory opioid receptor functions on opioid analgesia,tolerance, and dependence

Electrophysiologic studies of opioid effects on nociceptive types of dorsal root ganglion (DRG) neurons in organotypic cultures have shown that morphine and mostμ, δ, and κ opioid agonists can elicit bimodal excitatory as well as inhibitory modulation of the action potential duration (APD) of these cells. Excitatory opioid effects have been shown to be mediated by opioid receptors that are coupled via Gs to cyclic AMP-dependent ionic conductances that prolong the APD, whereas inhibitory opioid effects are mediated by opioid receptors coupled via Gi/Go to ionic conductuances that shorten the APD. Selective blockade of excitatory opioid receptor functions by low (ca. pM) concentrations of naloxone, naltrexone, etorphine and other specific agents markedly increases the inhibitory potency of morphine or other bimodally acting agonists and attenuates development of tolerance/dependence. These in vitro studies have been confirmed by tail-flick assays showin that acute co-treatment of mice with morphine plus ultra-low-dose naltrexone or etorphine remarkably enhances the antinociceptive potency of morphine whereas chronic co-treatment attenuates development of tolerance and naloxone-precipitated withdrawal-jumping symptoms. Special issue dedicated to Dr. Eric J. Simon.     

Effects of extracellular concentration of calcium and intensity of stimulation on short-term plasticity in single inhibitory synapses between cultured hippocampal neurons

We studied the characteristics of short-term plasticity in inhibitory synapses of cultured neurons of the rat hippocampus. In our experiments, we used techniques of voltage clamp in the whole-cell configuration and of local electrical stimulation (pairs of stimuli were applied to a single synaptic terminal of the GABA-ergic neuron under conditions of the blockade of spreading excitation). We demonstrated that an increase or a decrease in the extracellular concentration of calcium ions ([Ca²⁺]_o) results in modifications of the pattern of this plasticity. Depression of the second postsynaptic response under conditions of normal [Ca²⁺]_o was characterized by a paired-pulse ratio (PPR) equal, on average, to 0.78 ± 0.04 (n = 5). With a decrease in the [Ca²⁺]_o to 0.5 mM, depression was changed to facilitation (PPR = 1.17 ± 0.08, n = 5), while with a rise in the [Ca²⁺]_o to 5.0 mM, depression became more clearly pronounced (PPR = 0.48 ± 0.03, n = 5). Alterations of responses, which were determined by a decrease or an increase in the [Ca²⁺]_o, differed significantly from those related to a decrease or an increase in the amplitude of presynaptic stimulation. Analysis of the parameters of the pairs of evoked inhibitory postsynaptic currents under conditions of various [Ca²⁺]_o and different intensities of stimulation of the presynaptic terminal allows us to conclude that in these terminals calcium-dependent (and, probably, also voltage-dependent) mechanisms underlying control of short-term synaptic plasticity are present. Neirofiziologiya/Neurophysiology, Vol. 38, No. 2, pp. 103–112, March–April, 2006.     

Adenylate cyclase-mediated modulation of interaction between excitatory and inhibitory synaptic influences on smooth muscles

We found that nonadrenergic inhibitory synaptic potentials (ISP) induced by intramural stimulation in atropine-treated smooth muscles of the guinea-pig large intestine demonstrated no changes upon the influence of an activator of adenylate cyclase, forskolin. This indicates that cAMP-dependent pathways are not involved in the generation of ISP. However, in these muscles with no atropine pretreatment ISP were suppressed by forskolin; intramural stimulation evoked in these smooth muscle cells M-cholinergic excitatory synaptic potentials (ESP) instead of ISP. An increase in the intracellular cAMP concentration due to application of its membrane-penetrating form, dibutyryl-cAMP, did not mimic the above-described effect of forskolin. Hence, it can be supposed that the effect of forskolin on inhibitory synaptic transmission in the atropine-untreated smooth muscles is not related to changes in the intracellular cAMP level; this effect is determined by other mechanisms. The above differences between the effects of forskolin on ISP in the atropine-treated and atropine-untreated smooth muscle strips indicate that the interaction of intracellular signal pathways (probably, through protein G_q/11), which is observed with activation of adenylate cyclase, occurs under conditions of simultaneous activation of M cholinoreceptors and purinoreceptors. The pattern of adenylate cyclase-mediated modulation of inhibitory effects of purinergic neurons on smooth muscles does not allow us to rule out the possibility of involvement of interstitial cells of Cajal as a relay link providing this synaptic effect. Transmission of excitation from cholinergic nerve terminals to smooth muscles is realized without the participation of the interstitial cells of Cajal.Neirofiziologiya/Neurophysiology, Vol. 36, Nos. 5/6, pp. 438–445, September–December, 2004.This revised version was published online in April 2005 with a corrected cover date and copyright year.     

辛伐他汀在大鼠体内药动学性别差异的研究

目的:研究Wistar大鼠单次灌服辛伐他汀后体内药代动力学的性别差异。方法:利用高效液相色谱方法检测大鼠血浆中辛伐他汀浓度,采用非房室模型法计算各自药动学参数。结果:雌、雄大鼠体内Cmax分别为(144.66±22.31)ng·mL~(-1)和(165.91±52.50)ng·mL~(-1);t_(1/2)分别为(4.74±1.19)h和(14.98±6.64)h;AUC_(0-10)分别为(0.990±0.19)μg.h·mL~(-1)和(0.726±0.15)μg·h·mL~(-1);AUC0-∞分别为(1.62±0.47)μg·h·mL~(-1)和(2.19±0.62)μg·h·mL~(-1);MRT分别为(9.69±1.60)h和(23.08±8.89)h,经t-检验,雌、雄大鼠主要药动学参数t_(1/2)、AUC_(0-10)、MRT均有统计学显著性差异(p<0.01)。结论:辛伐他汀在大鼠体内的药代动力学存在明显的性别差异,辛伐他汀在雌性大鼠体内代谢较快。     

成人与儿童下呼吸道标本病原菌分布差异的比对与耐药性分析

目的调查研究温州市中西医结合医院温州市儿童医院成人与儿童病区下呼吸道标本病原菌的分布差异与抗生素耐药性分析。方法对2010年7月至2011年6月的所有成人与儿童下呼吸道感染患者的临床标本（痰,咽拭）进行微生物检验并统计分析。结果成人感染以非发酵细菌为主,并且出现MDR/PDR现象;儿童细菌性感染以肠杆菌细菌为主;G＋菌感染还是以金黄色葡萄为主,也有MRSA菌株出现,未超过15%,远远低于成人水平。铜绿假单胞菌检出率占成人下呼吸道感染的首位,头孢三、四代对成人铜绿假单胞菌耐药性在50%左右;阿米卡星有很好的敏感性,耐药率为5.2%;头孢哌酮/舒巴坦的耐药率已达20.59%;碳青霉烯类抗生素的耐药率在50%左右。成人鲍曼不动杆菌只有米诺环素、头孢哌酮/舒巴坦有较好的敏感性,耐药率在10%左右;并且已经出现全耐药菌株。儿童检出病原菌中对头孢哌酮/舒巴坦、碳青霉烯类抗生素未发现耐药菌株,对头孢三、四代仍有较好的敏感性,还没出现高耐菌株。头孢三、四代对成人肺炎克雷伯菌耐药性已高达75%左右;头孢哌酮/舒巴坦、碳青霉烯类抗生素的耐药率将达20%。儿童中MRSA检出率为13.32%,成人已高达72.15%,未发现对万古霉素、替考拉宁、利那唑胺耐药菌株。结论儿童与成人在下呼吸道感染病原菌分布与耐药性存在明显差异。应杜绝滥用抗生素,做到有的放矢。     

Sterilization of allograft bone: effects of gamma irradiation on allograft biology and biomechanics

Gamma irradiation from Cobalt 60 sources has been used to terminally sterilize bone allografts for many years. Gamma radiation adversely affects the mechanical and biological properties of bone allografts by degrading the collagen in bone matrix. Specifically, gamma rays split polypeptide chains. In wet specimens irradiation causes release of free radicals via radiolysis of water molecules that induces cross-linking reactions in collagen molecules. These effects are dose dependent and give rise to a dose-dependent decrease in mechanical properties of allograft bone when gamma dose is increased above 25 kGy for cortical bone or 60 kGy for cancellous bone. But at doses between 0 and 25 kGy (standard dose), a clear relationship between gamma dose and mechanical properties has yet to be established. In addition, the effects of gamma radiation on graft remodelling have not been intensively investigated. There is evidence that the activity of osteoclasts is reduced when they are cultured onto irradiated bone slices, that peroxidation of marrow fat increases apoptosis of osteoblasts; and that bacterial products remain after irradiation and induce inflammatory bone resorption following macrophage activation. These effects need considerably more investigation to establish their relevance to clinical outcomes. International consensus on an optimum dose of radiation has not been achieved due to a wide range of confounding variables and individual decisions by tissue banks. This has resulted in the application of doses ranging from 15 to 35 kGy. Here, we provide a critical review on the effects of gamma irradiation on the mechanical and biological properties of allograft bone.     

初始条件对高浓度乙醇连续发酵过程的影响及振荡行为提高发酵效率的机理分析

前期实验在稀释速率为0.027h-1的高浓度乙醇连续发酵过程中,发现了一种长周期、宽振幅的参数振荡现象。本实验进一步考察了不同稀释速率下的连续发酵过程,发现在稀释速率为0.04h-1条件下,也能出现类似的振荡现象;在稀释速率为0.027h-1或0.04h-1的条件下,改变系统的初始状态可以得到振荡和稳态两种不同的发酵过程。比较振荡和稳态过程的实验数据后,发现在稀释速率为0.04h-1的条件下,与稳态过程相比,振荡过程的平均残糖浓度降低了14.8%,平均乙醇浓度提高了12.6%,平均设备生产强度提高了12.3%。进一步分析表明:与稳态过程相比,振荡过程动力学行为不仅存在滞后,而且在相同残糖和乙醇浓度条件下,所对应的平均比生长速率提高了53.8%。     

Frequency and amplitude windows in the combined action of DC and low frequency AC magnetic fields on ion thermal motion in a macromolecule: theoretical analysis

We solved the differential equation describing combined action of DC and AC magnetic fields on thermal motion of ions in a biological macromolecule. The solution showed the occurrence of a new set of resonant peaks for ion oscillations under the influence of magnetic fields. After establishment of steady ion oscillations in the macromolecule interior that is well shielded from the action of small particles of the medium surrounding this molecule, the change in energy of ion thermal motion could be sufficient to alter the conformation state of the macromolecule. On this basis, a diversity of biological phenomena can be explained, including the appearance of the known "frequency" and "amplitude" windows, without any resort to the ideas of participation of cyclotron or parametric resonances in these effects.     

西南地区不同植被类型归一化植被指数与气候因子的相关分析

基于中国西南地区1982—2006年的归一化植被指数(NDVI)遥感数据集和气象数据,运用GIS技术对年均气温、年降水量和干旱指数进行插值,分析了西南地区不同植被类型(沼泽、灌丛、草丛、草原、草甸、针叶林、阔叶林、高山植被、栽培植被)NDVI的年际变化及其与气候因子的相关性.结果表明:研究期间,西南地区NDVI、年均气温、年降水量总体呈上升趋势,其中,年均气温的上升趋势达极显著水平,干旱指数则呈下降趋势;在9种植被类型中,沼泽和草丛NDVI呈下降趋势,且草丛的下降趋势达显著水平,其他7种植被类型的NDVI均呈上升趋势,且针叶林、草甸和高山植被的NDVI上升趋势达显著水平,灌丛NDVI呈极显著上升趋势.9种植被类型所在地区的年均气温均显著上升;年降水量的变化均不显著;沼泽、草丛和栽培植被所在地区的干旱指数呈上升趋势,草甸和高山植被所在地区的干旱指数显著下降,其他4种植被类型所在地区的干旱指数呈不明显的下降趋势.研究区灌丛和针叶林NDVI与年均气温呈显著正相关,灌丛和草甸NDVI与干旱指数呈显著负相关.在保持其他2个气候因子不变的情况下,针叶林、阔叶林、高山植被NDVI与年均气温的相关性最大,草丛NDVI与年降水...     

黄土高原泾河流域长时间序列的归一化植被指数动态变化及其驱动因素分析

泾河流域土地开发历史悠久, 是黄土高原水土流失的典型区域。研究气候变化和人类活动影响下泾河流域的植被覆盖变化及其原因, 对黄土高原的植被恢复、水土保持和景观管理等都具有重要意义。该研究应用GIMMS归一化植被指数NDVI、土地覆盖分类数据和气候数据, 采用趋势分析和相关分析方法, 研究了泾河流域1982-2005年植被覆盖变化趋势及其驱动因素。研究表明: 泾河流域24年间79.64%的区域NDVI无显著变化趋势, NDVI趋势显著增加的区域占16.33%, 主要集中在流域中部和南部, NDVI趋势显著减小的区域占4.03%, 主要集中在流域北部。流域所有气象站点的降水量均无显著变化趋势, 气温均呈显著升高趋势。分析发现气候变化不能很好地解释NDVI趋势的空间分异, 人为因素更为重要。从土地利用分析结果来看, NDVI不同趋势下各土地利用类型比例无明显变化, 但NDVI显著增加区以耕地为主, 显著减小区以草地为主, 由此推断NDVI的显著增加趋势主要由耕地NDVI增加引起, 显著减小趋势可能与林地减少和草地退化有关。通过分析不同分区的土地利用数据和社会经济资料, 着重探讨了造成植被覆盖显著变化趋势的人为因素。     

Expression of the difference between the Cold (Han) and Hot (Re) natures of traditional Chinese medicines (Strobal and Rhubarb) based on the cold/hot plate differentiating assay

In this study, objective differences between the Cold (Han) and Hot (Re) nature of traditional Chinese medicines, e.g. Strobal and Rhubarb, are determined by using a cold/hot plate differentiation technology. A novel, self-designed cold/hot plate differentiating instrument, with methodological study, was used to investigate the intervention of Strobal and Rhubarb on the temperature tropism of mice. Compared with the ICR and BALB/c mice, it was found that KM mice on the cold/hot plate were more sensitive to the change of temperature, within the tolerant temperature range of 15—40℃. The temperature tropism behavior of mice is influenced by treatment with Rhubarb and Strobal, as is the activity of ATPase in liver tissue. These trends are consistent with the definition of the Cold/Hot nature of Chinese medicines based on traditional Chinese medicinal theory. This study showed that the differences of the Cold/Hot nature of traditional Chinese medicines. might be objectively represented by the temperature tropism of animal by means of cold/hot differentiating assay.     

肥胖与肠道菌群相关性的研究热点、前沿和演变路径可视化分析

目的 了解肥胖与肠道菌群相关性文献的科研合作网络特征、研究热点和前沿及其演变历史等,为后续研究提供参考依据.方法 以“obesity”和“gut microbiota”为主题词,基于Web of Science数据库的检索结果,利用VOSviewer和CiteSpace软件对国际肥胖与肠道菌群类研究领域文献进行计量学和...     

Differential analysis of Bacillus anthracis after pX01 plasmid curing and comprehensive data on Bacillus anthracis infection in macrophages and glial cells

Bacillus anthracis is a gram-positive bacterial organism responsible for anthrax. This organism has two pathogenic plasmids: pX01 and pX02. The genetic function of pX01, which comprises about 198 kb, is not known, except for a region called the pathogenic island, which contains three genes-pag, lef, and cya-that code for three toxic proteins. A 2-D difference gel electrophoresis (2-D DIGE) system was used to verify the existence of proteins controlled by the pX01 plasmid, and protein regulation data were obtained using DeCyder software. A total of 1728 proteins were identified in the wild-type strain of this organism and 1684 in the pX01 plasmid. Twenty-seven of these proteins disappeared and eight appeared when the pX01 plasmid was removed. An additional 52 proteins were downregulated and 15 were upregulated when this plasmid was removed. A total of 102 proteins have been identified using the MALDI-TOF method of analysis, including 49 whose functions are unknown. Among these, 31 participate in metabolic processes, two in cellular processes, 15 in the processing of genetic information, and five in the processing of extracellular information. Another seven proteins participate in bacterial virulence and pathogenesis. We investigated the functions of these proteins in other bacteria, particularly the B. anthracis derivative H9041. Bacterial growth differed between pX01+/pX02+ B. anthracis and its pX01-/pX02+ derivative as did the cytotoxicity of macrophages infected by pX01+/pX02+ B. anthracis and the pX01-pX02+ derivative. We also found that S100B protein levels increased in the host infected with pX01+/pX02+ B. anthracis or its pX01-/pX02+ derivative. These data suggest that the pX01 plasmid plays a key role in the regulation of protein functions in B. anthracis.