Kiragasi Beril, Wondolowski Joyce, Li Yan, Dickman Dion K
Department of Neurobiology, University of Southern California, Los Angeles, CA 90089, USA; USC Neuroscience Graduate Program, University of Southern California, Los Angeles, CA 90089, USA.
Department of Neurobiology, University of Southern California, Los Angeles, CA 90089, USA.
Cell Rep. 2017 Jun 27;19(13):2694-2706. doi: 10.1016/j.celrep.2017.06.003.
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 calcium sensitivity 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.
稳态信号系统被认为与其他形式的可塑性相互作用，以确保神经传递水平灵活而稳定。神经递质受体在这一过程中的作用，除了介导神经传递本身之外，尚不清楚。通过正向遗传学筛选，我们发现果蝇海人酸型离子型谷氨酸受体亚基DKaiR1D是突触强度逆行性稳态增强所必需的。DKaiR1D在突触前运动神经元中是必需的，定位于活性区附近，并赋予基线突触传递钙敏感性以稳健性。急性药理学阻断DKaiR1D会破坏稳态可塑性，表明该受体是这一过程表达所必需的，与发育作用不同。最后，我们证明通过DKaiR1D的钙通透性对于基线突触传递是必需的，但对于稳态信号则不是。我们提出DKaiR1D是一种谷氨酸自身受体，可促进突触强度和可塑性的稳健性，并具有活性区特异性。
