Nature neurosci—胶质细胞研究重磅突破：小脑胶质细胞的吞噬作用决定小鼠运动学习能力

中文摘要

突触修剪是学习和记忆神经环路重塑的一个基本过程。越来越多的证据表明，胶质细胞通过突触吞噬参与了神经环路的塑造。然而，神经胶质细胞参与突触修剪是否在记忆形成中起作用仍不清楚。使用新开发的吞噬报告转基因小鼠和三维超微结构表征，研究人员发现小脑Bergmann胶质细胞（BG）的突触吞噬在小鼠小脑依赖性运动学习中经常发生。他们观察到BG突触前和突触后“啃食”的增加，以及学习后树突棘体积的减少。用膜联蛋白V阻断胶质细胞的吞咽作用抑制了树突棘体积的减少和运动学习的提高。这些结果表明，在运动学习过程中，BG通过突触吞噬，有助于重塑成熟的小脑皮层环路。

英文摘要

Synaptic pruning is a fundamental process of neuronal circuit refinement in learning and memory. Accumulating evidence suggests that glia participates in sculpting the neuronal circuits through synapse engulfment. However, whether glial involvement in synaptic pruning has a role in memory formation remains elusive. Using newly developed phagocytosis reporter mice and three-dimensional ultrastructural characterization, we found that synaptic engulfment by cerebellar Bergmann glia (BG) frequently occurred upon cerebellum-dependent motor learning in mice. We observed increases in pre- and postsynaptic nibbling by BG along with a reduction in spine volume after learning. Pharmacological blockade of engulfment with Annexin V inhibited both the spine volume reduction and overnight improvement of motor adaptation. These results indicate that BG contribute to the refinement of the mature cerebellar cortical circuit through synaptic engulfment during motor learning.

参考文献：Synaptic pruning through glial synapse engulfment upon motor learning.Nat Neurosci. 2022 Nov;25(11):1458-1469. doi: 10.1038/s41593-022-01184-5. Epub 2022 Nov 1.

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