BACKGROUND Microglia play a key role in neuronal circuit and synaptic maturation in the developing brain. In the healthy adult, however, their role is less clear: microglial hyperactivation in adults can be detrimental to memory due to excessive synaptic pruning, yet learning and memory can also be impaired in the absence of these cells. In this study, we therefore aimed to determine how microglia contribute to short-term memory in healthy adults. METHODS To this end, we developed a Cx3cr1-Dtr transgenic Wistar rat with a diphtheria toxin receptor (Dtr) gene inserted into the fractalkine receptor (Cx3cr1) promoter, expressed on microglia and monocytes. This model allows acute microglial and monocyte ablation upon application of diphtheria toxin, enabling us to directly assess microglia's role in memory. RESULTS Here, we show that short-term memory in the novel object and place recognition tasks is entirely unaffected by acute microglial ablation. However, when microglia repopulate the brain after depletion, learning and memory performance in these tasks is improved. This transitory memory enhancement is associated with an ameboid morphology in the newly repopulated microglial cells and increased astrocyte density that are linked with a higher density of mature hippocampal synaptic spines and differences in pre- and post-synaptic markers. CONCLUSIONS These data indicate that glia play a complex role in the healthy adult animal in supporting appropriate learning and memory and that subtle changes to the function of these cells may strategically enhance memory.

中文翻译：

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胶质重塑增强了Wistar大鼠的短期记忆表现。

背景小胶质细胞在发育中的大脑的神经元回路和突触成熟中起关键作用。然而，在健康的成年人中，它们的作用尚不清楚：由于过度的突触修剪，成年人中的小胶质细胞过度活化会损害记忆，但是在缺乏这些细胞的情况下，学习和记忆也会受到损害。因此，在这项研究中，我们旨在确定小胶质细胞如何促进健康成年人的短期记忆。方法为此，我们开发了一只Cx3cr1-Dtr转基因Wistar大鼠，其白喉毒素受体（Dtr）基因插入了分链蛋白受体（Cx3cr1）启动子中，在小胶质细胞和单核细胞上表达。该模型允许在应用白喉毒素后进行急性小胶质细胞和单核细胞消融，使我们能够直接评估小胶质细胞在记忆中的作用。结果在这里，我们显示，在新型对象和位置识别任务中的短期记忆完全不受急性小胶质细胞消融的影响。但是，当小胶质细胞耗竭后重新进入大脑后，这些任务中的学习和记忆能力就会得到改善。这种短暂的记忆增强与新近重新分布的小神经胶质细胞中的变形虫形态和星形胶质细胞密度增加有关，而星形胶质细胞密度与成熟海马突触棘突的较高密度以及突触前和突触后标记的差异有关。结论这些数据表明，神经胶质细胞在健康的成年动物中，在支持适当的学习和记忆方面起着复杂的作用，这些细胞功能的细微变化可能会从战略上增强记忆力。