Graduate School of Medical Sciences, Kyushu University, 812-8582, Fukuoka, Japan.
Graduate School of Medical Sciences, Kyushu University, 812-8582, Fukuoka, Japan
eNeuro. 2023 Nov 10;10(11). doi: 10.1523/ENEURO.0323-23.2023. Print 2023 Nov.
During early development, neurons in the brain often form excess synaptic connections. Later, they strengthen some connections while eliminating others to build functional neuronal circuits. In the olfactory bulb, a mitral cell initially extends multiple dendrites to multiple glomeruli but eventually forms a single primary dendrite through the activity-dependent dendrite pruning process. Recent studies have reported that microglia facilitate synapse pruning during the circuit remodeling in some systems. It has remained unclear whether microglia are involved in the activity-dependent dendrite pruning in the developing brains. Here, we examined whether microglia are required for the developmental dendrite pruning of mitral cells in mice. To deplete microglia in the fetal brain, we treated mice with a colony-stimulating factor 1 receptor (CSF1R) inhibitor, PLX5622, from pregnancy. Microglia were reduced by >90% in mice treated with PLX5622. However, dendrite pruning of mitral cells was not significantly affected. Moreover, we found no significant differences in the number, density, and size of excitatory synapses formed in mitral cell dendrites. We also found no evidence for the role of microglia in the activity-dependent dendrite remodeling of layer 4 (L4) neurons in the barrel cortex. In contrast, the density of excitatory synapses (dendritic spines) in granule cells in the olfactory bulb was significantly increased in mice treated with PLX5622 at postnatal day (P) 6, suggesting a role for the regulation of dendritic spines. Our results indicate that microglia do not play a critical role in activity-dependent dendrite pruning at the neurite level during early postnatal development in mice.
在大脑早期发育过程中，神经元经常形成过多的突触连接。后来，它们通过活动依赖性的树突修剪过程，增强一些连接，同时消除其他连接，以建立功能性神经元回路。在嗅球中，一个僧帽细胞最初会向多个肾小球延伸多个树突，但最终通过活动依赖性的树突修剪过程形成一个单一的主树突。最近的研究报告称，在某些系统的回路重塑过程中，小胶质细胞促进突触修剪。目前尚不清楚小胶质细胞是否参与了发育中大脑的活动依赖性树突修剪。在这里，我们研究了小胶质细胞是否参与了小鼠僧帽细胞的发育性树突修剪。为了耗尽胎儿大脑中的小胶质细胞，我们用集落刺激因子 1 受体（CSF1R）抑制剂 PLX5622 处理怀孕的小鼠。PLX5622 处理的小鼠中小胶质细胞减少了 >90%。然而，僧帽细胞的树突修剪并没有受到显著影响。此外，我们发现僧帽细胞树突上形成的兴奋性突触的数量、密度和大小没有显著差异。我们也没有发现小胶质细胞在桶状皮层 L4 神经元的活动依赖性树突重塑中的作用证据。相比之下，在 PLX5622 处理的小鼠中，嗅球颗粒细胞中的兴奋性突触（树突棘）密度在出生后第 6 天显著增加，表明小胶质细胞在树突棘调节中起作用。我们的结果表明，小胶质细胞在小鼠出生后早期发育过程中的神经突起水平的活动依赖性树突修剪中没有发挥关键作用。
