The role of cAMP in synaptic homeostasis in response to environmental temperature challenges and hyperexcitability mutations.

The role of cAMP in synaptic homeostasis in response to environmental temperature challenges and hyperexcitability mutations.
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DOI:
10.3389/fncel.2015.00010
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发表时间:
2015
影响因子:
5.3
通讯作者:
Wu CF
Wu CF
中科院分区:
医学2区
文献类型:
--
作者:
Ueda A;Wu CF

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内稳态是生理系统在环境或实验损伤后恢复功能平衡的能力,突触内稳态已在许多物种中被证明是在遗传或药理学破坏后实现的。在环境挑战中,对极端温度的稳态反应对动物在自然条件下的生存至关重要。我们之前报道过果蝇幼虫神经肌肉连接处(NMJs)的轴突末端树杈在高温下增强;然而,尽管突触钮扣数量增加,兴奋性连接电位(EJPs)的振幅保持不变。在这里,我们确定了在高温(高温,29°C)饲养的幼虫中这种自我平衡调节的细胞基础。我们发现单个突触钮扣局部记录的突触电流不受饲养温度(<15°C至bb0 - 30°C)的影响。然而,高温饲养减少了量子大小(自发微型EJP的振幅,或mEJPs),这补偿了突触释放位点数量的增加,以保持正常的EJP大小。量子大小的减少是由于突触后肌纤维输入阻力的减少,表明膜面积的增加与高温下突触的生长相匹配。有趣的是,在高温饲养后,编码腺苷酸环化酶(AC)的rutabaga (rut)突变在突触后肌肉细胞的量子大小和输入阻力方面没有明显变化,这表明车辙AC在果蝇温度诱导的突触稳态中起重要作用。这扩展了我们之前在超兴奋突变体(如slowpoke)中发现的依赖车辙的突触稳态。在缓慢的幼虫中,通过上调突触前激振器(Sh) IA电流来限制过度的递质释放,以及突触后谷氨酸受体重组来减少量子大小,可以部分改善BK通道功能的缺乏。
Homeostasis is the ability of physiological systems to regain functional balance following environment or experimental insults and synaptic homeostasis has been demonstrated in various species following genetic or pharmacological disruptions. Among environmental challenges, homeostatic responses to temperature extremes are critical to animal survival under natural conditions. We previously reported that axon terminal arborization in Drosophila larval neuromuscular junctions (NMJs) is enhanced at elevated temperatures; however, the amplitude of excitatory junctional potentials (EJPs) remains unaltered despite the increase in synaptic bouton numbers. Here we determine the cellular basis of this homeostatic adjustment in larvae reared at high temperature (HT, 29°C). We found that synaptic current focally recorded from individual synaptic boutons was unaffected by rearing temperature (<15°C to >30°C). However, HT rearing decreased the quantal size (amplitude of spontaneous miniature EJPs, or mEJPs), which compensates for the increased number of synaptic releasing sites to retain a normal EJP size. The quantal size decrease is accounted for by a decrease in input resistance of the postsynaptic muscle fiber, indicating an increase in membrane area that matches the synaptic growth at HT. Interestingly, a mutation in rutabaga (rut) encoding adenylyl cyclase (AC) exhibited no obvious changes in quantal size or input resistance of postsynaptic muscle cells after HT rearing, suggesting an important role for rut AC in temperature-induced synaptic homeostasis in Drosophila. This extends our previous finding of rut-dependent synaptic homeostasis in hyperexcitable mutants, e.g., slowpoke (slo). In slo larvae, the lack of BK channel function is partially ameliorated by upregulation of presynaptic Shaker (Sh) IA current to limit excessive transmitter release in addition to postsynaptic glutamate receptor recomposition that reduces the quantal size.
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发表时间: 2010-02-03
期刊: The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子: --
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期刊: JOURNAL OF COMPARATIVE PHYSIOLOGY
影响因子: --
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发表时间: 1984-01-01
影响因子: 2.5
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通讯作者: ZVI, S
DOI: 10.1073/pnas.0400773101
发表时间: 2004-03-23
影响因子: 11.1
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通讯作者: Rössler, W
DOI: 10.1080/01677060490894522
发表时间: 2004-04-01
影响因子: 1.9
作者:
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通讯作者: Wu, CF