Department of Physiology and Pharmacology, Sapienza University of Rome, Rome, Italy.
Neurophysiology and Neuropharmacology Inflammaging Unit, IRCCS Neuromed, Mediterranean Neurological Institute, Pozzilli, IS, Italy.
Glia. 2022 Jan;70(1):173-195. doi: 10.1002/glia.24101. Epub 2021 Oct 18.
Microglia cells are active players in regulating synaptic development and plasticity in the brain. However, how they influence the normal functioning of synapses is largely unknown. In this study, we characterized the effects of pharmacological microglia depletion, achieved by administration of PLX5622, on hippocampal CA3-CA1 synapses of adult wild type mice. Following microglial depletion, we observed a reduction of spontaneous and evoked glutamatergic activity associated with a decrease of dendritic spine density. We also observed the appearance of immature synaptic features and higher levels of plasticity. Microglia depleted mice showed a deficit in the acquisition of the Novel Object Recognition task. These events were accompanied by hippocampal astrogliosis, although in the absence ofneuroinflammatory condition. PLX-induced synaptic changes were absent in Cx3cr1 mice, highlighting the role of CX3CL1/CX3CR1 axis in microglia control of synaptic functioning. Remarkably, microglia repopulation after PLX5622 withdrawal was associated with the recovery of hippocampal synapses and learning functions. Altogether, these data demonstrate that microglia contribute to normal synaptic functioning in the adult brain and that their removal induces reversible changes in organization and activity of glutamatergic synapses.
小胶质细胞是调节大脑中突触发育和可塑性的活跃参与者。然而，它们如何影响突触的正常功能在很大程度上是未知的。在这项研究中，我们描述了通过给予 PLX5622 实现药理学小胶质细胞耗竭对成年野生型小鼠海马 CA3-CA1 突触的影响。在小胶质细胞耗竭后，我们观察到与树突棘密度降低相关的自发和诱发谷氨酸能活性的减少。我们还观察到不成熟突触特征的出现和更高水平的可塑性。小胶质细胞耗竭的小鼠在新物体识别任务的获得中表现出缺陷。这些事件伴随着海马星形胶质细胞增生，尽管没有神经炎症的情况。在 Cx3cr1 小鼠中，PLX 诱导的突触变化不存在，突出了 CX3CL1/CX3CR1 轴在小胶质细胞控制突触功能中的作用。值得注意的是，PLX5622 撤回后小胶质细胞的再定植与海马突触和学习功能的恢复有关。总的来说，这些数据表明小胶质细胞有助于成年大脑中正常的突触功能，并且它们的去除会引起谷氨酸能突触的组织和活性的可逆变化。
