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药理学阻断下强直刺激后突触形态的独特变化。

Unique changes in synaptic morphology following tetanization under pharmacological blockade.

作者信息

Weeks Andrew C W, Ivanco Tammy L, Leboutillier Janelle C, Marrone Diano F, Racine Ronald J, Petit Ted L

机构信息

Department of Psychology, Nipissing University, North Bay, Ontario, Canada.

出版信息

Synapse. 2003 Jan;47(1):77-86. doi: 10.1002/syn.10113.

DOI:10.1002/syn.10113
PMID:12422376
Abstract

Long-term potentiation (LTP) in the hippocampus has been associated with changes in synaptic morphology. Whether these changes are LTP-dependent or simply a result of electrophysiological stimulation has not yet been fully determined. This study involved an examination of synaptic morphology in the rat dentate gyrus 24 h after electrophysiological stimulation sufficient to induce LTP. In one group, ketamine, a competitive NMDA antagonist, was injected prior to stimulation to block the formation of LTP. Synaptic morphological quantification included estimating the total number of synapses per neuron, determining synaptic curvature and the presence of synaptic perforations, and measuring the maximal PSD profile length of the synapses. The results indicated that most of the changes observed following the induction of LTP (increases in the proportion of concave-shaped synapses, increases in perforated concave synapses, and a decrease in the length of nonperforated concave synapses) are not observed under ketamine blockade, suggesting that they are LTP-specific and not simply the result of tetanic stimulation. Ketamine was associated, however, with several novel structural changes including a decrease in the length of the perforations in the concave perforated synapses, a reduction in the number of convex perforated synapses, and a nonlayer-specific increase in synaptic length compared to controls. Based on previous research, this combination of morphological characteristics is potentially less efficacious, which suggests that synapses that are tetanized but not potentiated, due to pharmacological blockade, appear to undergo opposing, compensatory, or homeostatic changes. These results support the suggestion that synaptic morphology changes are both stimulation- and area-specific, are highly complex, and depend on the specific local physiology.

摘要

海马体中的长时程增强(LTP)与突触形态的变化有关。这些变化是依赖于LTP还是仅仅是电生理刺激的结果尚未完全确定。本研究对大鼠齿状回在足以诱导LTP的电生理刺激后24小时的突触形态进行了检查。在一组中,在刺激前注射竞争性NMDA拮抗剂氯胺酮以阻断LTP的形成。突触形态定量包括估计每个神经元的突触总数、确定突触曲率和突触穿孔的存在以及测量突触的最大突触后致密部(PSD)轮廓长度。结果表明,在氯胺酮阻断下未观察到诱导LTP后观察到的大多数变化(凹形突触比例增加、穿孔凹形突触增加以及非穿孔凹形突触长度减少),这表明它们是LTP特异性的,而不仅仅是强直刺激的结果。然而,氯胺酮与几种新的结构变化有关,包括凹形穿孔突触中穿孔长度的减少、凸形穿孔突触数量的减少以及与对照组相比突触长度的非层特异性增加。基于先前的研究,这种形态特征的组合可能效率较低,这表明由于药理学阻断而被强直刺激但未增强的突触似乎经历了相反、补偿或稳态变化。这些结果支持了突触形态变化具有刺激特异性和区域特异性、高度复杂且依赖于特定局部生理学的观点。

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Unique changes in synaptic morphology following tetanization under pharmacological blockade.药理学阻断下强直刺激后突触形态的独特变化。
Synapse. 2003 Jan;47(1):77-86. doi: 10.1002/syn.10113.
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Sequential changes in the synaptic structural profile following long-term potentiation in the rat dentate gyrus. II. Induction/early maintenance phase.大鼠齿状回长期增强后突触结构轮廓的顺序变化。II. 诱导/早期维持阶段。
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Sequential changes in the synaptic structural profile following long-term potentiation in the rat dentate gyrus: I. The intermediate maintenance phase.大鼠齿状回长时程增强后突触结构轮廓的顺序变化:I. 中间维持阶段。
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Long-term potentiation is associated with changes in synaptic ultrastructure in the rat neocortex.长期增强作用与大鼠新皮层突触超微结构的变化有关。
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Remodelling of synaptic morphology but unchanged synaptic density during late phase long-term potentiation (LTP): a serial section electron micrograph study in the dentate gyrus in the anaesthetised rat.晚期长时程增强(LTP)期间突触形态重塑但突触密度不变:麻醉大鼠齿状回的连续切片电子显微镜研究
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Long-term synaptic morphometry changes after induction of long-term potentiation and long-term depression in the dentate gyrus of awake rats are not simply mirror phenomena.在清醒大鼠齿状回中诱导长时程增强和长时程抑制后,长期的突触形态测量变化并非简单的镜像现象。
Eur J Neurosci. 2004 Apr;19(8):2310-8. doi: 10.1111/j.0953-816X.2004.03334.x.
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Structural synaptic correlate of long-term potentiation: formation of axospinous synapses with multiple, completely partitioned transmission zones.长时程增强的结构突触关联:具有多个完全分隔的传递区的轴棘突触的形成。
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Contribution of NMDA receptor channels to the expression of LTP in the hippocampal dentate gyrus.N-甲基-D-天冬氨酸(NMDA)受体通道对海马齿状回长时程增强(LTP)表达的作用。
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Structural synaptic plasticity associated with the induction of long-term potentiation is preserved in the dentate gyrus of aged rats.与长时程增强诱导相关的结构性突触可塑性在老年大鼠的齿状回中得以保留。
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Developmental lead (Pb) exposure reduces the ability of the NMDA antagonist MK-801 to suppress long-term potentiation (LTP) in the rat dentate gyrus, in vivo.发育期铅暴露会降低NMDA拮抗剂MK-801在体内抑制大鼠齿状回长时程增强(LTP)的能力。
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引用本文的文献

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Synaptic loss and retention of different classic cadherins with LTP-associated synaptic structural remodeling in vivo.突触丢失和保留不同经典钙黏着蛋白与体内 LTP 相关突触结构重塑。
Hippocampus. 2012 Jan;22(1):17-28. doi: 10.1002/hipo.20859. Epub 2010 Sep 16.
2
Caloric restriction eliminates the aging-related decline in NMDA and AMPA receptor subunits in the rat hippocampus and induces homeostasis.热量限制消除了大鼠海马体中与衰老相关的NMDA和AMPA受体亚基的下降,并诱导内稳态。
Exp Neurol. 2007 Jul;206(1):70-9. doi: 10.1016/j.expneurol.2007.03.026. Epub 2007 Apr 4.
3
Expression of long-term potentiation in aged rats involves perforated synapses but dendritic spine branching results from high-frequency stimulation alone.
老年大鼠中长时程增强的表达涉及穿孔突触,但树突棘分支仅由高频刺激引起。
Hippocampus. 2004;14(2):255-64. doi: 10.1002/hipo.10172.
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Long-term potentiation: outstanding questions and attempted synthesis.长期增强作用:突出问题与综合探讨
Philos Trans R Soc Lond B Biol Sci. 2003 Apr 29;358(1432):829-42. doi: 10.1098/rstb.2002.1242.