慢性氟中毒致学习记忆损伤的脑内突触机制

探讨了慢性氟中毒致学习记忆损伤的脑内机制.选用初断乳雄性SD大鼠192只,随机分为4组:1个对照组,饮用自来水;3个分别饮用15,30和60 mg/L Na F溶液的染氟组.染氟期为18月.每3月用开场行为和Morris水迷宫法检测大鼠的学习记忆行为;分别在染氟中期(9月)和染氟结束后(18月)分2批断头处死大鼠,进行脑海马突触体膜流动性和海马CA3区突触后致密蛋白-95(PSD-95)表达水平等检测.结果表明:慢性氟中毒致大鼠自发活动和探究行为显著或极显著抑制,空间学习记忆能力显著下降;脑海马突触膜流动性、PSD-95表达水平均显著下降.提示慢性氟中毒致脑海马突触体膜流动性和突触后致密蛋白-95表达水平的改变可能是慢性氟中毒致学习记忆损伤的脑内突触机制之一.     

硒氟联用对小鼠脑内PSD厚度及SOD活性的影响

采用饮水加氟、加硒的方法,用电镜和计算机图像分析仪分析研究了小鼠学习记忆相关脑区——海马CA\-3区GrayI型突触后致密物质(PSD)厚度的变化,并用生化方法测定了其脑内SOD活性的变化.结果表明高氟能引起小鼠脑内海马CA\-3区突触后致密物质厚度极显著变小(P＜0.01或P＜0.001)的病理性变化,并能降低其脑内SOD活性;适当量的硒可拮抗氟的这种作用,但硒量过高或过低则与氟产生协同毒性作用.提示一定量的硒对氟致小鼠脑内突触结构损伤有改善作用,并且这种改善作用可能和硒提高其脑内\{SOD\}活性有关.     

二十二碳六烯酸改善老年大鼠嗅觉记忆行为潜在机制的研究

实验研究二十二碳六烯酸(DHA)对老年大鼠嗅觉辨识记忆行为和嗅球脂肪酸以及GAP-43和PSD-95蛋白表达的影响.实验每天按照180 mg·kg-1灌喂24月龄老年大鼠49 d.在43, 44和45 d进行嗅觉辨识学习记忆行为的训练,第46,47,48 d进行嗅觉辨识学习记忆行为学实验,第49 d处死.实验结果表明: DHA能显著提高老年大鼠嗅觉辨识记忆能力, DHA组老年大鼠嗅球中n3不饱和脂肪酸与老年组相比含量显著提高,嗅球中n6多不饱和脂肪酸与老年组相比含量显著降低.另外,DHA 的含量在DHA组中明显比老年组增高,n3/n6多不饱和脂肪酸的比值也明显增大,但是AA的含量则显著减少.用 Western bolting方法分析生长相关蛋白(GAP-43) 和突触后致密物质95的表达后显示：DHA能提高老年大鼠嗅球GAP-43和PSD-95的表达水平.     

衰老大鼠学习行为与海马突触相关蛋白表达的研究

研究衰老大鼠的学习行为与海马内突触相关蛋白的表达．运用Y-迷宫方法对幼年对照组（断乳期）和老年期（22月龄）雄性Sprague—Dawley大鼠进行Y-迷宫空间学习记忆行为训练,之后利用免疫组化和Western blot方法检测2组大鼠海马内突触素（synaptophysin,Syn）、生长相关蛋白（GAP-43）的表达情况．研究结果：（1）2组相比,老年组的学习能力较强,幼年对照组记忆能力较强（P〈0．05）;（2）生长相关蛋白GAP-43在老年组海马内的表达显著高于幼年对照组;而突触素的表达低于幼年对照组（P〈0．01）．提示,GAP-43和突触素可能参与大鼠空间分辨学习记忆的过程,老年大鼠的中枢神经系统保持着潜在的神经元退化修复的功能．     

大鼠下丘脑和背侧丘脑在空间学习记忆时突触素的变化

目的：探讨空间学习记忆时下丘脑和背侧丘脑突触素的变化。方法：用水迷宫训练大鼠21d建立空间辨别性学习记忆模型,随后停止训练,分别停止3、7及14d,用免疫组化方法和图像分析技术,检测了突触素在大鼠下丘脑、背侧丘脑的表达。结果：对照组大鼠突触素的表达较强,免疫反应产物叶点状颗粒,在下丘脑的上部和下部分布较少,中部较多。在背侧丘脑颗粒大小比较一致,发布较均匀。模型组大鼠下丘脑和背侧丘脑的突触素颗粒大小都较均匀,光密度值与对照组比较无显著性差异（P＞0．05）,随着停止训练时间的延长,突触素的表达也未见减弱。结论：提示空间学习记忆可能未导致下丘脑、背侧丘脑区突触数量的变化。     

突触界面结构参数的定量分析法

本实验用IBM-PC微机图像分析系统对小鼠海马与大脑皮层的Gray I型突触电镜图像进行了定量分析,测定了突触后膜致密物质厚度、突触间隙宽度、突触界面曲率和突触活性带长度等结构参数。以DGAVP引起突触结构变化为实例检验了这种定量分析法的可行性与可靠性。本文详细介绍了测量方法和步骤。实验将系统校正、图像测定及数据处理等过程融为一体,既快速又精确,与传统手工测量方法相比,证明了此法的优越性与实用性。     

大气可吸入颗粒物(PM_(10))暴露诱导大鼠神经功能损伤的突触机制研究

为了探讨可吸入颗粒物(PM10)对神经功能损伤的突触机制,研究通过建立大鼠气管注入染毒模型,考察了不同浓度PM10暴露对突触素(SYP)、突触后致密物(PSD-95)、NMDA受体2B亚型(NR2B)、磷酸化胞外信号调节激酶(p-ERK)和环磷腺苷效应元件结合蛋白(p-Creb)表达水平的影响,并对突触超微结构进行观察。结果表明,PM10暴露增加SYP、PSD-95和NR2B的表达,上调p-ERK和p-Creb的表达水平,并呈现一定的剂量-效应关系,大鼠海马区突触超微结构的变化与上述结果相吻合,这意味着PM10暴露可能通过改变突触可塑性引起神经功能损伤。     

烟碱和一氧化碳对大鼠学习记忆及脑发育的影响

通过观察烟碱和一氧化碳(CO)对大鼠学习记忆和脑发育的影响,利用Y型迷宫测试学习记忆,利用电镜技术观测脑超微结构。得出烟碱可使学习记忆能力下降(P<0.05),使大脑皮层厚度(P<0.05)及突触数密度(P相似文献   

电针对AD大鼠学习记忆能力及神经元凋亡的影响

目的:探讨电针对AD模型大鼠学习记忆能力和神经元凋亡的影响.方法:将40只健康SD大鼠随机分为正常组、假手术组、模型组和电针组,采用A1-40注入大鼠双侧Meynert核建立AD模型,电针组采用电针治疗,治疗一个月后用水迷宫试验测定各组大鼠学习记忆能力,然后处死大鼠检测海马及皮质的神经元凋亡百分比.结果:模型组出现学习记忆障碍,呈渐进性加重,4周时更为显著,而且在海马区和皮质区神经元有较高的凋亡比例,电针组有明显改善(P<0.01).结论:Meynert核注射A可使大鼠发生较持久的学习记忆功能障碍及胆碱能神经元凋亡,电针治疗可改善AD大鼠学习记忆能力,抑制神经元凋亡.     

神经系统信号传导的研究进展

 人脑由上千亿的神经细胞组成,他们通过突触相互连接并传递信息。突触为相邻神经元之间的点状连结区域,包括有突触前膜、突触间隙和突触后膜。突触前膜可以分泌一些化学物质——神经递质（如多巴胺、去甲肾上腺素和５－羟色胺等）,这些递质通过突触间隙与突触后膜上的受体结合,将信号——神经冲动——从一个神经细胞传至另一个神经细胞,以实现神经的信号传导功能。神经系统的信号传导是学习记忆、感觉、睡眠、运动等各种脑正常功能的物质基础。神经系统信号的传导障碍可以引起许多神经和精神疾病,因此,神经的信号传导理论也是神经精神病理学的基础。     

Structural basis of long-term potentiation in single dendritic spines

Dendritic spines of pyramidal neurons in the cerebral cortex undergo activity-dependent structural remodelling that has been proposed to be a cellular basis of learning and memory. How structural remodelling supports synaptic plasticity, such as long-term potentiation, and whether such plasticity is input-specific at the level of the individual spine has remained unknown. We investigated the structural basis of long-term potentiation using two-photon photolysis of caged glutamate at single spines of hippocampal CA1 pyramidal neurons. Here we show that repetitive quantum-like photorelease (uncaging) of glutamate induces a rapid and selective enlargement of stimulated spines that is transient in large mushroom spines but persistent in small spines. Spine enlargement is associated with an increase in AMPA-receptor-mediated currents at the stimulated synapse and is dependent on NMDA receptors, calmodulin and actin polymerization. Long-lasting spine enlargement also requires Ca2+/calmodulin-dependent protein kinase II. Our results thus indicate that spines individually follow Hebb's postulate for learning. They further suggest that small spines are preferential sites for long-term potentiation induction, whereas large spines might represent physical traces of long-term memory.     

猫舌感觉传入神经形成主要类型突触的研究

目的：研究舌传入神经形成的突触类型及分布规律,探讨舌传人纤维形成的主要类型突触。方法：按传入纤维性质和终止核团,分4个单项组：快适应纤维终止于三叉神经脊束核组（FA-VS）,快适应纤维终止于三叉神经脑桥核组（FA-VP）,慢适应纤维终止于三叉神经脊束核组（SA-VS）。慢适应纤维终止于三叉神经脑桥核组（SA-VP）;4个复合组：快适应纤维组（FA）,慢适应纤维组（SA）,三叉神经脊束核组（VS）,三叉神经脑桥核组（VP）组。在确定了脑干内的舌传入纤维后进行细胞内注射,电镜连续切片观察,分析突触类型。结果：突触按组成数目分单纯型、中间型和复杂型3种类型。各组中问型突触出现频率最多,组间数据较接近;单纯型和复杂型突触出现频率相对较少,组问数据较分散;FA-VS组单纯型出现频率最多,SA-VP复杂型出现频率最多;各组单纯型突触增、减时其复杂型突触相应减、增。结论：中间型突触为主要类型突触;单纯型和复杂型突触为辅助型突触;单纯型和复杂型突触有完全相反的势态分布;单纯型和复杂型突触也有相应增、减分布规律。     

Investigation of the synaptic device based on the resistive switching behavior in hafnium oxide

Metal-oxide based electronics synapse is promising for future neuromorphic computation application due to its simple structure and fab-friendly materials. HfOx resistive switching memory has been demonstrated superior performance such as high speed, low voltage, robust reliability, excellent repeatability, and so on. In this work, the HfOx synaptic device was investigated based on its resistive switching phenomenon. HfOx resistive switching device with different electrodes and dopants were fabricated. TiN/Gd:HfOx/Pt stack exhibited the best synaptic performance, including controllable multilevel ability and low training energy consumption. The training schemes for memory and forgetting were developed.     

远志皂苷对小鼠行为习得及海马CA3区突触形态的影响

为了探讨远志皂苷对小鼠学习能力及海马CA3区突触形态的影响,把30只小鼠随机分为2组:药物组灌胃生药量为4.50 g/kg的远志皂苷溶液,对照组灌胃相等剂量的生理盐水,14 d后进行行为学训练,期间继续给药10 d.训练结束后,各取7只小鼠检测海马CA3区突触密度、活性带长度、突触间隙宽度、PSD厚度及穿孔突触的比例....     

Induction of dendritic spines by an extracellular domain of AMPA receptor subunit GluR2

Synaptic transmission from excitatory nerve cells in the mammalian brain is largely mediated by AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid)-type glutamate receptors located at the surface of dendritic spines. The abundance of postsynaptic AMPA receptors correlates with the size of the synapse and the dimensions of the dendritic spine head. Moreover, long-term potentiation is associated with the formation of dendritic spines as well as synaptic delivery of AMPA receptors. The molecular mechanisms that coordinate AMPA receptor delivery and spine morphogenesis are unknown. Here we show that overexpression of the glutamate receptor 2 (GluR2) subunit of AMPA receptors increases spine size and density in hippocampal neurons, and more remarkably, induces spine formation in GABA-releasing interneurons that normally lack spines. The extracellular N-terminal domain (NTD) of GluR2 is responsible for this effect, and heterologous fusion proteins of the NTD of GluR2 inhibit spine morphogenesis. We propose that the NTD of GluR2 functions at the cell surface as part of a receptor-ligand interaction that is important for spine growth and/or stability.     

Locally dynamic synaptic learning rules in pyramidal neuron dendrites

Long-term potentiation (LTP) of synaptic transmission underlies aspects of learning and memory. LTP is input-specific at the level of individual synapses, but neural network models predict interactions between plasticity at nearby synapses. Here we show in mouse hippocampal pyramidal cells that LTP at individual synapses reduces the threshold for potentiation at neighbouring synapses. After input-specific LTP induction by two-photon glutamate uncaging or by synaptic stimulation, subthreshold stimuli, which by themselves were too weak to trigger LTP, caused robust LTP and spine enlargement at neighbouring spines. Furthermore, LTP induction broadened the presynaptic-postsynaptic spike interval for spike-timing-dependent LTP within a dendritic neighbourhood. The reduction in the threshold for LTP induction lasted approximately 10 min and spread over approximately 10 microm of dendrite. These local interactions between neighbouring synapses support clustered plasticity models of memory storage and could allow for the binding of behaviourally linked information on the same dendritic branch.     

氧化锌/氧化钽双介质层忆阻器的突触特性分析

人工突触的开发是模拟人脑功能的关键。忆阻器由于具备独特的电阻记忆行为,在人工突触研究领域得到广泛的关注。氧化钽和氧化锌均是优良的忆阻器材料,鉴于有关ZnO/TaOx双介质忆阻器突触特性的研究较少,本文将氧化锌介质层引入Ti/TaOx/ITO忆阻器中拟改善其突触性能。研究发现,器件Ti/ZnO/TaOx/ITO在功耗和电导调制线性度方面皆有改善,并有着电阻渐变的行为,利于器件突触功能的实现及应用。为此对Ti/ZnO/TaOx/ITO双介质层器件进行了电压脉冲训练,并成功模拟了学习饱和、经验学习以及短时程记忆向长时程记忆转变等生物突触行为。     

Experience-dependent and cell-type-specific spine growth in the neocortex

Functional circuits in the adult neocortex adjust to novel sensory experience, but the underlying synaptic mechanisms remain unknown. Growth and retraction of dendritic spines with synapse formation and elimination could change brain circuits. In the apical tufts of layer 5B (L5B) pyramidal neurons in the mouse barrel cortex, a subset of dendritic spines appear and disappear over days, whereas most spines are persistent for months. Under baseline conditions, new spines are mostly transient and rarely survive for more than a week. Transient spines tend to be small, whereas persistent spines are usually large. Because most excitatory synapses in the cortex occur on spines, and because synapse size and the number of alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptors are proportional to spine volume, the excitation of pyramidal neurons is probably driven through synapses on persistent spines. Here we test whether the generation and loss of persistent spines are enhanced by novel sensory experience. We repeatedly imaged dendritic spines for one month after trimming alternate whiskers, a paradigm that induces adaptive functional changes in neocortical circuits. Whisker trimming stabilized new spines and destabilized previously persistent spines. New-persistent spines always formed synapses. They were preferentially added on L5B neurons with complex apical tufts rather than simple tufts. Our data indicate that novel sensory experience drives the stabilization of new spines on subclasses of cortical neurons. These synaptic changes probably underlie experience-dependent remodelling of specific neocortical circuits.     

Long-term sensory deprivation prevents dendritic spine loss in primary somatosensory cortex

A substantial decrease in the number of synapses occurs in the mammalian brain from the late postnatal period until the end of life. Although experience plays an important role in modifying synaptic connectivity, its effect on this nearly lifelong synapse loss remains unknown. Here we used transcranial two-photon microscopy to visualize postsynaptic dendritic spines in layer I of the barrel cortex in transgenic mice expressing yellow fluorescent protein. We show that in young adolescent mice, long-term sensory deprivation through whisker trimming prevents net spine loss by preferentially reducing the rate of ongoing spine elimination, not by increasing the rate of spine formation. This effect of deprivation diminishes as animals mature but still persists in adulthood. Restoring sensory experience after adolescent deprivation accelerates spine elimination. Similar to sensory manipulation, the rate of spine elimination decreases after chronic blockade of NMDA (N-methyl-D-aspartate) receptors with the antagonist MK801, and accelerates after drug withdrawal. These studies of spine dynamics in the primary somatosensory cortex suggest that experience plays an important role in the net loss of synapses over most of an animal's lifespan, particularly during adolescence.