Maintenance of homeostatic plasticity at the Drosophila neuromuscular synapse requires continuous IP3-directed signaling
Maintenance of homeostatic plasticity at the Drosophila neuromuscular synapse requires continuous IP3-directed signaling
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DOI：
10.7554/elife.39643
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发表时间：
2019-06-10
期刊：
影响因子：
7.7
通讯作者：
Frank, C. Andrew
中科院分区：
文献类型：
--
作者：
James, Thomas D.;Zwiefelhofer, Danielle J.;Frank, C. Andrew
突触和回路依靠神经可塑性来调整输出并满足生理需求。稳态突触可塑性的形式通过对抗不稳定的扰动来赋予突触稳定性。果蝇幼虫神经肌肉接头（NMJ）是一种具有稳态可塑性的模型突触。在NMJ，稳态系统检测受损的突触后对神经递质的敏感性，并激活逆行信号，通过调节神经递质的释放来恢复突触功能。这一过程已被分为时间上不同的阶段，诱导和维护。一个流行的假设是，一个共同的机制管理这两个阶段。在这里，我们表明这两个阶段是可分离的。结合遗传学、药理学和电生理学，我们发现由PLC β、三磷酸肌醇（IP3）、IP3受体和Ryanodine受体组成的信号系统仅用于维持稳态可塑性。我们还发现，NMJ是能够诱导稳态信号，即使当其持续的维护过程是absent.Editorial说明：这篇文章已经通过了编辑过程中，作者决定如何回应同行评议过程中提出的问题。审核编辑的评估是所有问题都已得到解决（见决定函）。
Synapses and circuits rely on neuroplasticity to adjust output and meet physiological needs. Forms of homeostatic synaptic plasticity impart stability at synapses by countering destabilizing perturbations. The Drosophila melanogaster larval neuromuscular junction (NMJ) is a model synapse with robust expression of homeostatic plasticity. At the NMJ, a homeostatic system detects impaired postsynaptic sensitivity to neurotransmitter and activates a retrograde signal that restores synaptic function by adjusting neurotransmitter release. This process has been separated into temporally distinct phases, induction and maintenance. One prevailing hypothesis is that a shared mechanism governs both phases. Here, we show the two phases are separable. Combining genetics, pharmacology, and electrophysiology, we find that a signaling system consisting of PLC beta, inositol triphosphate (IP3), IP3 receptors, and Ryanodine receptors is required only for the maintenance of homeostatic plasticity. We also find that the NMJ is capable of inducing homeostatic signaling even when its sustained maintenance process is absent.Editorial note: This article has been through an editorial process in which the authors decide how to respond to the issues raised during peer review. The Reviewing Editor's assessment is that all the issues have been addressed (see decision letter).