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首页> 外文期刊>The European Journal of Neuroscience >Neurotrophins act at presynaptic terminals to activate synapses among cultured hippocampal neurons.
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Neurotrophins act at presynaptic terminals to activate synapses among cultured hippocampal neurons.

机译:神经营养蛋白在突触前末端起作用,以激活培养的海马神经元之间的突触。

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We have recently demonstrated that embryonic E16 hippocampal neurons grown in cultures are unable to form fast synaptic connections unless treated with BDNF or NT-3. This experimental system offers an opportunity to define the roles of neurotrophins in processes leading to formation of functional synaptic connections. We have used ultrastructural and electrophysiological methods to explore the cellular locations underlying neurotrophin action on synaptic maturation. The rate of spontaneous miniature excitatory postsynaptic currents (mEPSCs) evoked by hyperosmotic stimulation was 7-16-fold higher in neurotrophin-treated cells than in controls. In addition, the potent neurotransmitter-releasing drug alpha-latrotoxin was virtually ineffective in the control cells while it stimulated synaptic events in neurotrophin-treated cells. Likewise, the membrane-bound dye FM1-43 was taken up by terminals in neurotrophin-treated cultures five-fold more than in controls. Both the total number and the number of docked synaptic vesicles were increased by neurotrophin treatment. Activation of synaptic responses by neurotrophins occurred even when postsynaptic glutamate receptors and action potential discharges were pharmacologically blocked. These results are consistent with a presynaptic locus of action of neurotrophins to increase synaptic vesicle density which is critical for rapid synaptic transmission. They also suggest that neurotrophins can activate synapses in the absence of pre- and postsynaptic neuronal activity.
机译:我们最近已经证明,除非经过BDNF或NT-3处理,否则在培养物中生长的胚胎E16海马神经元无法形成快速的突触连接。该实验系统为定义神经营养蛋白在导致功能性突触连接形成的过程中的作用提供了机会。我们已经使用超微结构和电生理方法来探索神经营养蛋白对突触成熟的潜在细胞定位。高渗透压刺激诱发的自发性微型兴奋性突触后突触电流(mEPSCs)在神经营养蛋白处理的细胞中比对照组高7-16倍。另外,有效的神经递质释放药物α-拉毒素在对照细胞中实际上无效,同时它刺激了神经营养蛋白处理的细胞中的突触事件。同样,膜结合染料FM1-43在神经营养蛋白处理的培养物中的末端所吸收的量是对照的五倍。神经营养蛋白治疗增加了突触小泡的总数和对接数量。即使在药理学上阻断了突触后谷氨酸受体和动作电位的放电,神经营养蛋白也会激活突触反应。这些结果与神经营养蛋白增加突触囊泡密度的突触前作用轨迹一致,这对于快速突触传递至关重要。他们还表明,在没有突触前和突触后神经元活性的情况下,神经营养蛋白可以激活突触。

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