A Presynaptic Glutamate Receptor Subunit Confers Robustness to Neurotransmission and Homeostatic Potentiation
A Presynaptic Glutamate Receptor Subunit Confers Robustness to Neurotransmission and Homeostatic Potentiation
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DOI：
10.1016/j.celrep.2017.06.003
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发表时间：
2017-06-27
期刊：
影响因子：
8.8
通讯作者：
Dickman, Dion K.
中科院分区：
文献类型：
--
作者：
Kiragasi, Beril;Wondolowski, Joyce;Dickman, Dion K.
稳态信号系统被认为与其他形式的可塑性相互作用，以确保灵活而稳定的神经传递水平。除了介导神经传递本身之外，神经递质受体在此过程中的作用尚不清楚。通过正向遗传筛选，我们发现果蝇红藻氨酸型离子型谷氨酸受体亚基 DKaiR1D 是突触强度逆行、稳态增强所必需的。 DKaiR1D 在突触前运动神经元中是必需的，位于活动区附近，并赋予基线突触传递的钙敏感性稳健性。 DKaiR1D 的急性药理学阻断会破坏稳态可塑性，表明该受体是该过程表达所必需的，与发育作用不同。最后，我们证明 DKaiR1D 的钙渗透性对于基线突触传递是必要的，但对于稳态信号传导不是必需的。我们认为 DKaiR1D 是一种谷氨酸自身受体，可通过活性区特异性提高突触强度和可塑性的鲁棒性。
Homeostatic signaling systems are thought to interface with other forms of plasticity to ensure flexible yet stable levels of neurotransmission. The role of neurotransmitter receptors in this process, beyond mediating neurotransmission itself, is not known. Through a forward genetic screen, we have identified the Drosophila kainate-type ionotropic glutamate receptor subunit DKaiR1D to be required for the retrograde, homeostatic potentiation of synaptic strength. DKaiR1D is necessary in presynaptic motor neurons, localized near active zones, and confers robustness to the calciumsensitivity of baseline synaptic transmission. Acute pharmacological blockade of DKaiR1D disrupts homeostatic plasticity, indicating that this receptor is required for the expression of this process, distinct from developmental roles. Finally, we demonstrate that calcium permeability through DKaiR1D is necessary for baseline synaptic transmission, but not for homeostatic signaling. We propose that DKaiR1D is a glutamate autoreceptor that promotes robustness to synaptic strength and plasticity with active zone specificity.