Department of Pharmacology and Department of Pharmacy of the Second Affiliated Hospital, Key Laboratory of Medical Neurobiology of The Ministry of Health of China, School of Basic Medical Sciences, Zhejiang University School of Medicine, Hangzhou, 310058, China.
Department of Rehabilitation Medicine, Huzhou Central Hospital, Affiliated Huzhou Hospital, Zhejiang University School of Medicine, Huzhou, 313000, China.
Cell Mol Life Sci. 2024 Mar 4;81(1):116. doi: 10.1007/s00018-023-05111-0.
Microglia regulate synaptic function in various ways, including the microglial displacement of the surrounding GABAergic synapses, which provides important neuroprotection from certain diseases. However, the physiological role and underlying mechanisms of microglial synaptic displacement remain unclear. In this study, we observed that microglia exhibited heterogeneity during the displacement of GABAergic synapses surrounding neuronal soma in different cortical regions under physiological conditions. Through three-dimensional reconstruction, in vitro co-culture, two-photon calcium imaging, and local field potentials recording, we found that IL-1β negatively modulated microglial synaptic displacement to coordinate regional heterogeneity in the motor cortex, which impacted the homeostasis of the neural network and improved motor learning ability. We used the Cre-Loxp system and found that IL-1R1 on glutamatergic neurons, rather than that on microglia or GABAergic neurons, mediated the negative effect of IL-1β on synaptic displacement. This study demonstrates that IL-1β is critical for the regional heterogeneity of synaptic displacement by coordinating different actions of neurons and microglia via IL-1R1, which impacts both neural network homeostasis and motor learning ability. It provides a theoretical basis for elucidating the physiological role and mechanism of microglial displacement of GABAergic synapses.
小胶质细胞通过多种方式调节突触功能，包括小胶质细胞对周围 GABA 能突触的移位，这为某些疾病提供了重要的神经保护作用。然而，小胶质细胞突触移位的生理作用和潜在机制仍不清楚。在这项研究中，我们观察到在生理条件下，不同皮质区域神经元胞体周围 GABA 能突触的移位过程中小胶质细胞表现出异质性。通过三维重建、体外共培养、双光子钙成像和局部场电位记录，我们发现 IL-1β 负调控小胶质细胞的突触移位，以协调运动皮层的区域异质性，从而影响神经网络的内稳态并改善运动学习能力。我们使用 Cre-Loxp 系统发现，谷氨酸能神经元上的 IL-1R1，而不是小胶质细胞或 GABA 能神经元上的 IL-1R1，介导了 IL-1β 对突触移位的负向作用。这项研究表明，IL-1β 通过 IL-1R1 协调神经元和小胶质细胞的不同作用，对于突触移位的区域异质性至关重要，这既影响神经网络的内稳态，又影响运动学习能力。它为阐明 GABA 能突触小胶质细胞移位的生理作用和机制提供了理论依据。
