GABA Excitation during Development: the Nature of the Nurture

The lecture describes the role of GABA-mediated synaptic excitation during early ontogenesis.     

Dendritic and Synaptic Effects in Systems of Coupled Cortical Oscillators

We explore the influence of synaptic location and form on the behavior of networks of coupled cortical oscillators. First, we develop a model of two coupled somatic oscillators that includes passive dendritic cables. Using a phase model approach, we show that the synchronous solution can change from a stable solution to an unstable one as the cable lengthens and the synaptic position moves further from the soma. We confirm this prediction using a system of coupled compartmental models. We also demonstrate that when the synchronous solution becomes unstable, a bifurcation occurs and a pair of asynchronous stable solutions appear, causing a phase lag between the cells in the system. Then using a variety of coupling functions and different synaptic positions, we show that distal connections and broad synaptic time courses encourage phase lags that can be reduced, eliminated, or enhanced by the presence of active currents in the dendrite. This mechanism may appear in neural systems where proximal connections could be used to encourage synchrony, and distal connections and broad synaptic time courses could be used to produce phase lags that can be modulated by active currents.     

Cerebral Cortex Synaptic Heavy Mitochondria May Represent the Oldest Synaptic Mitochondrial Population: Biochemical Heterogeneity and Effects of L-Acetylcarnitine

The microheterogeneous nature of intrasynaptic mitochondria has been demonstrated and iswidely accepted. However, evidence is still lacking about the role played by the differentintrasynaptic mitochondrial subpopulations. The data obtained support the hypothesis thatheavy mitochondria could represent old mitochondrial populations: in fact, in addition tothe well known impairment of typical mitochondrial functions, they possess the highest levelsof hydroperoxides and their fatty acids pattern is completely modified. The qualitative andquantitative fatty acid modifications suffered by these organelles deeply altered theirprotein/lipid ratio, thus modifying their mode of action. The present work also collects a large bodyof evidence that a subchronic L-acetylcarnitine treatment in 28 days does not structurallyaffect both nonsynaptic and intrasynaptic mitochondria of normal rat in asteady-statemetabolic condition.     

The Autapse: A Simple Illustration of Short-Term Analog Memory Storage by Tuned Synaptic Feedback

According to a popular hypothesis, short-term memories are stored as persistent neural activity maintained by synaptic feedback loops. This hypothesis has been formulated mathematically in a number of recurrent network models. Here we study an abstraction of these models, a single neuron with a synapse onto itself, or autapse. This abstraction cannot simulate the way in which persistent activity patterns are distributed over neural populations in the brain. However, with proper tuning of parameters, it does reproduce the continuously graded, or analog, nature of many examples of persistent activity. The conditions for tuning are derived for the dynamics of a conductance-based model neuron with a slow excitatory autapse. The derivation uses the method of averaging to approximate the spiking model with a nonspiking, reduced model. Short-term analog memory storage is possible if the reduced model is approximately linear and if its feedforward bias and autapse strength are precisely tuned.     

谷氨酸转运体对癫痫持续状态大鼠突触可塑性的影响

探讨了在大鼠癫痫持续状态模型,谷氨酸转运体功能改变对突触可塑性的影响.健康成年雄性Wistar大鼠((304.06±13.79)g)随机分为5组,短期癫痫实验组(SE)及其对照组(SC),长期癫痫实验组(LE)及其对照组(LC),健康对照组(Sham).匹鲁卡品皮下注射(25 mg/kg)建立癫痫模型,建模14天后SE和LE组大鼠右侧海马内注射谷氨酸转运体抑制剂TBOA(7.5 nmol,lμ1),SC和LC组注射相同剂量的人工脑脊液.注射药物2 h后,SE和SC组检测脑电图(EEG):药物注射后2周,LJ巳和LC组检测内嗅区前穿通纤维-海马齿状回(PP-DG)长时程增强(LTP)和EEG.电生理学检测后动物灌流取脑做Fluoro-Jade-B染色.结果表明:脑电功率谱分析,SE组theta波段能量较sc组明显下降(P＜0.05),LE组与其对照Lc组相比,EEG的也theta波段能量无明显差异(P＞0.05);LTP检测显示.LE组与对照LC组相比,兴奋性突触后电位(EPSP)斜率升高(P＜0.01);Fluoro-Jade-B染色显示,LE组与对照LC组相比,给予TBOA 2周后细胞变性明显增加.结果提示,癫痫持续状态后,海马神经元损伤,TBOA导致谷氨酸转运体功能障碍,加重癫痫所至神经元损伤,对海马区突触可塑性产生影响.     

Localized Bumps of Activity Sustained by Inhibition in a Two-Layer Thalamic Network

Based on head direction experiments in rats, the existence of localized bumps of thalamic activity has been proposed. We computationally demonstrate the existence of a novel class of localized bump solutions in a two-layer conductance-based thalamic network and analyze the mechanisms behind these stable patterns. In contrast to previous models of bump activity, here inhibition plays a crucial role in initially spreading neuronal firing and in subsequently sustaining it. In our model, we incorporate local strong, fast GABA(A) inhibition and diffuse weak, slow GABA(B) inhibition, based on previous biophysical experiments. These forms of inhibition contribute in different, yet complementary, ways to the observed pattern formation.     

Cell-Type Specificity of Callosally Evoked Excitation and Feedforward Inhibition in the Prefrontal Cortex

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孕期地塞米松暴露对大鼠子代海马神经元增殖以及突触可塑性的影响

地塞米松是一种糖皮质激素药物,具有抗炎、抑制免疫等多种药理作用,广泛应用于治疗多种疾病。临床上常使用地塞米松来促进早产儿的肺成熟以及预防胎儿呼吸窘迫综合征。目前的流行病学以及试验研究表明,地塞米松孕期暴露会增加子代患软骨病、肾脏损伤等疾病的风险。为了探究孕期地塞米松暴露(prenatal dexamethasone exposure,PDE)对大鼠子代胎鼠海马神经元增殖发育以及胎鼠海马突触可塑性形成的影响,对孕中晚期Wistar大鼠皮下注射地塞米松(0.2 mg·kg^-1·d^-1),对照组注射等剂量0.9%氯化钠溶液。收集GD20子代海马,采用实时荧光定量PCR以及Western blot法对海马神经增殖、突触可塑性形成和APPL1(adaptor protein containing pH domain,PTB domain and leucine zipper motif 1)进行相关功能检测,并进一步使用投射电镜观察海马突触超微结构。结果显示,与空白对照组相比,PDE胎海马Ki67、增殖细胞核抗原(proliferating cell ...     

Effects of Long-Term Hypoxia/Hypoglycemia on Synaptic Transmission between the CA3 and CA1 Zones in Rat Hippocampal Slices

On rat hippocampal slices using a standard patch-clamp technique in the whole-cell configuration, we studied the effects of long-term (40 to 60 min) hypoxia/hypoglycemia (HH) on excitatory postsynaptic currents (EPSC) evoked by stimulation of Schaffer collaterals in the cells of the CA1 zone. In addition to the earlier described effect of an immediate drop in the EPSC amplitude, a significant transient increase in its amplitude 30-50 min after the beginning of HH was observed. A pharmacologically isolated NMDA component of excitatory synaptic events underwent similar changes: 30-50 min after the blockade of NMDA receptor-mediated current, a fast recovery of its amplitude to the control (or even higher) values occurred. A blocker of NMDA/glutamate (Glu) receptors, D-aminophosphonovaleric acid (D-APV), and a competitive nonspecific antagonist of metabotropic Glu receptors, (RS)--methyl-4-carboxyphenylglycine – (RS)-MCPG – did not influence the HH-induced initial suppression of synaptic transmission but completely eliminated its delayed recovery. Our findings allow us to suppose that NMDA receptors, as well as metabotropic Glu receptors, play important roles in the cascade of biochemical reactions resulting in death of hippocampal pyramidal cells in the course of and after long-term ischemia in vivo.     

NMDA-Independent Long-Term Depression of Synaptic Transmission in the Hippocampus: Mechanisms of Induction and Effects of Nootropic Drugs

In studies on transversal slices of the rat dorsal hippocampus, we found that low-frequency tetanic stimulation of the medial perforant pathway (2 sec^-1, 7.5 min) results in long-term depression (LTD) of field EPSP of granular cells in the dentate gyrus. This synaptic plasticity phenomenon was weakened by calmodulin, nitric oxide synthase, and protein kinase C inhibitors, trifluoperazine (1 M), N-nitro-L-arginine (5 M), and polymixin B (50 M), respectively, but was enhanced by a nonselective inhibitor of cAMP phosphodiesterases, 1-isobuthyl-3-methylxanthine (100 M), and a calcineurin inhibitor, cyclosporin A (50 M). The nootropic activity-possessing drugs piracetam, carbacetam, and etimizole suppressed, in a dose-dependent manner, the induction and expression of the studied form of LTD of synaptic transmission, but glycine did not. We assume that Ca²⁺- and protein kinase G-mediated increase in the activity of calmodulin is the main link in the induction of this LTD form. Calmodulin, via NO synthase and adenylate cyclase, increases the activities of protein kinase C, a substrate of the latter, and inhibitor 1. Under the influence of piracetam, carbacetam, and etimizole, the calmodulin concentration in the cytoplasm of dendritic spines attains a level sufficient for activation of Ca²⁺/calmodulin-dependent protein kinase, which provides for the phosphorylation of AMPA receptors and interferes with the development of LTD of synaptic transmission.     

Complex NAPL Site Characterization Using Fluorescence Part 2: Analysis of Soil Matrix Effects on the Excitation/Emission Matrix

Commercially available cone penetrometer (CPT)fluorescence based sensor platforms have been used to detect non-aqueous phase liquids (NAPLs), such as petroleum oils and lubricants, in situf or more than a decade. These approaches have also been used to detect dense non-aqueous phase liquid (DNAPL) source zones by detecting commingled oilsfuels, and naturally occurring organic materials entrained by DNAPLs and carried to depths below the water table. Several neat NAPLs and mixtureswere added to various soil types and analyzedfor specific fluorescence characteristics to determine the optimal excitation source for site characterization efforts. Using excitationlemission matrices (EEMs), we demonstrate that an optimized excitation wavelength can be determinedfor specific fiuowphores within the NAPL mixtures, and that available systems can be ranked based on the specific contaminant and site soil types. An optimal excitation wavelength yields the maximum fluorescence within an EEM spectrum. We ranked commercially available cone penetrometer fluorescence detection systems according to the potential for ease of detection based on maximum fluorescence response. When soils were added tocomplexNAPLmixtures,analytefluorescence emissionwasattenuatedinpreferential portions of the EEM, leading to differences in the optimal excitation source wavelength. Furthermore, impure silica-containing minerals impact the emission signal, potentially leading to incorrect conclusionsf or several commercially available systems. Our find ings suggest that afrequency-agile (e.g., tunable excitation source) probe system would be superior to any other system commercially available, provided the system would be relatively easy to operate and would have rapid in-situ EEM generating capabilitiesfo r optimization in the field.     

Synaptic inhibition of smooth muscles of the human colon: Effects of vitamin B6 and its derivatives

Spontaneous activity, which is manifested as slow depolarization waves and action potentials, is observed in most (81%) smooth muscles (SMs) of the circular layer of the human colon. Independently of the type of pathology, inhibitory junction potentials (IJPs) in SMs of various parts of the human colon are evoked by intramural stimulation; ranges of parameters of these potentials were comparable with those observed in muscle intestinal fragments isolated at a distance of several tens of centimeters from the zone of injury. In muscle strips (MSs) of such fragments, pyridoxal-5′-phosphate (PPh) applied in different concentrations caused suppression of IJPs: in the concentration of 1·10⁻⁸ to 1·10⁻⁴ M it decreased the amplitude, and in the concentrations of 1·10⁻⁵ to 1·10⁻⁴ M and 1·10⁻⁴ M, respectively, it decreased rates of the half-amplitude rise and decay of these potentials. Pyridoxal (1·10⁻⁴ M) and 4-pyridoxolic acid (1·10⁻⁴ M) also caused a drop in the amplitude of IJPs; however, these agents influenced this parameter to a lesser extent, as compared with the effect of 1·10⁻⁴ M PPh. Pyridoxine (1·10⁻⁴ M) and pyridoxamine (1·10⁻⁴ M) evoked no significant changes in the parameters of IJPs in MSs of the human colon. Our data allow us to hypothesize that the suppressing effect of PPh on IJPs is determined by the presence of a purinergic component present in non-adrenergic inhibition of SMs of the human colon. Neirofiziologiya/Neurophysiology, Vol. 38, No. 4, pp. 269–279, July–August, 2006.     

千频交流电刺激在外周神经传导阻断中的作用

感觉、运动或自主神经系统的异常病理活动与疼痛和痉挛等多种神经机能障碍有关。千频交流电（kilohertz frequency alternating current，KHFAC）刺激是一种阻断异常病理活动在外周神经内传导的有效方法，它在缓解相关神经机能障碍方面具有临床应用潜力。KHFAC产生的神经传导阻断受千频信号波形和参数、阻断电极设置和位置以及神经纤维类型和直径等因素影响，具有快速性、可控性、可逆性、局部作用和副作用小的特点。但是，在产生完全传导阻断前，KHFAC首先在靶向神经上激活一簇高频初始放电，这种初始响应可能导致肌肉抽搐或疼痛感。同时，在撤去KHFAC后处于阻断状态的靶向神经需要经历一段时间才能恢复正常传导能力，这是该技术导致的后续效应。目前，关于KHFAC阻断神经传导的生物物理机制假说包括千频信号诱发K⁺通道激活和Na⁺通道失活。本文首先介绍了KHFAC技术的电生理实验研究方法和计算模型仿真方法，然后综述目前关于KHFAC作用下神经传导阻断的研究进展，重点论述初始响应特性及消除方法、传导阻断的后续效应、刺激波形和参数的影响、电极设置与位置的影响以及该技术潜在的临床应用，同时归纳KHFAC阻断神经传导的生物物理机制，最后对该技术未来的相关研究进行展望。     

Oscillatory Mechanisms in Pairs of Neurons Connected with Fast Inhibitory Synapses

We study dynamical mechanisms underlying oscillatory behavior in reciprocal inhibitory pairs of neurons, using a two-dimensionalcell model. We introduce one-and-two dimensional phase portraits to illustratethe behaviors, thus reducing the study of dynamical mechanisms to planar geometrical properties. We examined whether other mechanisms besides the escape and release mechanisms (Wang and Rinzel, 1992) might be needed for some cases of reciprocal inhibition, and show that, within the confines of a simple two-dimensional cell model, escape and releaseare sufficient for all cases. We divided the behaviors of a singlecell into six different types and examined the joint behaviors arising from every combination of pairs of cells with behaviors drawn from thesesix types. For the case of two quiescent cells or two cells eachhaving plateau potentials, bifurcation diagrams demonstrate therelations between synaptic threshold and synaptic strength necessaryfor oscillations by escape, oscillations by release, ornetwork-generated plateau potentials. Thus we clarify therelationship between plateau potentials and oscillations in a cell.Using the two dimensional cell model we examine 1:N beating betweencells and find that our simple model displays many of the essentialdynamical properties displayed by more sophisticated models, some ofwhich relate to thalamocortical spindling.     

三氧化二砷对黄鳝毒理学效应

以黄鳝为实验动物,研究了不同剂量的三氧化二砷对黄鳝的毒理学效应。采用鱼类致突变实验、鱼类红、白血球计数等方法,测定外周血白细胞数、红细胞微核和核异常以及肝脏过氧化氢酶（CAT）活性。结果发现：在低剂量范围内,随着三氧化二砷剂量的增加红细胞的微核率及核异常率逐渐增加、CAT活性升高,白细胞数则下降;至0．50mg／kg剂量时红细胞的微核率、核异常率,TLCAT活性均达最大值,而白细胞数达最低值;随着剂量的进一步增加红细胞的微核率、核异常率以及CAT活性均反而下降,白细胞数则上升。结果表明一定剂量三氧化二砷能明显影响黄鳝外周血细胞及肝脏CAT活性。     

真菌疏水蛋白的结构和功用

真菌疏水蛋白是一类具有强表面活性的分泌型小分子量蛋白质。疏水蛋白的重要特性是能在亲水—疏水界面通过自我组装形成一层紧密稳定的约10nm厚的两性蛋白膜。概述了疏水蛋白的结构和性质。总结了疏水蛋白的生理功能,并探讨它的各种应用。     

A Novel Nondevelopmental Role of the SAX-7/L1CAM Cell Adhesion Molecule in Synaptic Regulation in Caenorhabditis elegans

The L1CAM family of cell adhesion molecules is a conserved set of single-pass transmembrane proteins that play diverse roles required for proper nervous system development and function. Mutations in L1CAMs can cause the neurological L1 syndrome and are associated with autism and neuropsychiatric disorders. L1CAM expression in the mature nervous system suggests additional functions besides the well-characterized developmental roles. In this study, we demonstrate that the gene encoding the Caenorhabditis elegans L1CAM, sax-7, genetically interacts with gtl-2, as well as with unc-13 and rab-3, genes that function in neurotransmission. These sax-7 genetic interactions result in synthetic phenotypes that are consistent with abnormal synaptic function. Using an inducible sax-7 expression system and pharmacological reagents that interfere with cholinergic transmission, we uncovered a previously uncharacterized nondevelopmental role for sax-7 that impinges on synaptic function.     

低频电磁场对酿酒酵母蛋白质表达及酶活性的影响

【背景】低频电磁场(Lowfrequencyelectromagneticfield,LF-EMF)可导致一系列健康效应的事实已被普遍接受。【目的】进一步探究LF-EMF辐射对细胞蛋白质表达及相关酶活性的影响。【方法】以酿酒酵母为研究对象,采用50HzLF-EMF对其进行持续暴露辐射,随后对其胞内蛋白质表达、相关酶活性进行分析。【结果】LF-EMF辐射对酿酒酵母超氧化物歧化酶(Superoxide dismutase,SOD)、过氧化氢酶(Catalase,CAT)和苹果酸脱氢酶(Malate dehydrogenase,MDH)活性的影响存在先促进后抑制的趋势。辐射处理使SOD活性在72 h提高了43.18%,CAT活性在16 h提高了12.22%,MDH活性在20h提高了12.90%(P0.05);而LF-EMF辐射作用对乙醇脱氢酶(Alcohol dehydrogenase,ADH)和乳酸脱氢酶(Lactatedehydrogenase,LDH)的活性并未观察到显著的影响(P0.05)。此外,蛋白质电泳和蛋白质组学分析的结果表明,LF-EMF可改变酿酒酵母部分胞内蛋白质的表达水平,其中3种蛋白质的表达发生显著上调,9种蛋白质的表达发生显著下调(P0.05)。【结论】LF-EMF辐射可影响酿酒酵母的部分酶活性,改变其胞内部分蛋白质的表达水平。     

Establishment of a recording method for surface electromyography in the iliopsoas muscle

We examined the availability and reliability of surface electromyography (EMG) signals from the iliopsoas muscle (IL). Using serial magnetic resonance images from fifty healthy young males, we evaluated whether the superficial region of IL was adequate for attaching surface EMG electrodes. Subsequently, we assessed EMG cross-talk from the sartorius muscle (SA)—the nearest to IL—using a selective cooling method in fourteen subjects. The skin above SA was cooled, and the median frequencies of EMG signals from IL and SA were determined. The maximum voluntary contraction during isometric hip flexion was measured before and after selective cooling, and surface EMG signals from SA and IL were measured. The superficial area of IL was adequately large (13.2 ± 2.7 cm²) for recording surface EMG in all fifty subjects. The maximum perimeter for the medial–lateral skin facing IL was noted at a level 3–5 cm distal to the anterior superior iliac spine. Following cooling, the median frequency for SA decreased significantly (from 70.1 to 51.9 Hz, p < 0.001); however, that for IL did not alter significantly. These results demonstrated that EMG cross-talk from SA was negligible for surface EMG signals from IL during hip flexion.     

种植Bt玉米对土壤微生物活性和肥力的影响

在温室种植比较了美国Bt玉米(34B2 4 (Mon810 ) )与同源常规玉米(34B2 3)、中国Bt玉米(12 4 6×14 82 (Cry1A) )与常规玉米(农大3138)对土壤微生物活性和肥力的影响。结果表明,两个Bt玉米品种5次取样(2 5、39、5 3、6 7、82 d)的根际土壤中都能检测到Bt蛋白,含量在2 0～80 ng·g- 1 dry soil之间。4个处理土壤硝化作用和精氨酸氨化作用强度在所有取样时期均没有显著差异;土壤蔗糖酶、土壤蛋白酶和酸性磷酸酶活性则分别只在2 5 d(农大3138<34B2 4与12 4 6×14 82 )、6 7d(34B2 4 >12 4 6×14 82和农大3138)和6 7d(34B2 4 >其它3个处理)存在显著差异;土壤脱氢酶、土壤脲酶和土壤呼吸强度则在多数取样时期多个处理间存在显著差异,说明其与玉米品种特性关系密切,其中,土壤脱氢酶和脲酶活性的差异在两个Bt玉米品种、Bt与同源常规品种(34B2 4与34B2 3)、Bt与常规品种(12 4 6×14 82与农大3138)以及常规与常规品种(34B2 3与农大3138)之间均没有一致的规律,但34B2 4与34B2 3处理的土壤呼吸作用强度高于12 4 6×14 82与农大3138,说明种植该系列品种的土壤中微生物总活性较高、土壤代谢旺盛。82 d后4个处理土壤有机质、NPK全量与速效养分含量均没有显著差异。本试验观测期种植Bt玉米并没有导致土壤微生物活性和土