Maturation of the microglial population varies across mesolimbic nuclei

다국어 초록 (Multilingual Abstract)

Microglia play critical roles during CNS development and undergo dramatic changes in tissue distribution, morphology, and gene expression as they transition from embryonic to neonatal to adult microglial phenotypes. Despite the magnitude of these phenotypic shifts, little is known about the time course and dynamics of these transitions and whether they vary across brain regions. Here, we define the time course of microglial maturation in key regions of the basal ganglia in mice, where significant regional differences in microglial phenotype are present in adults. We found that microglial density peaks in the ventral tegmental area (VTA) and nucleus accumbens (NAc) during the third postnatal week, driven by a burst of microglial proliferation. Microglial abundance is then refined to adult levels through a combination of tissue expansion and microglial programmed cell death. This overproduction and refinement of microglia was significantly more pronounced in the NAc than in the VTA and was accompanied by a sharp peak in NAc microglial lysosome abundance in the third postnatal week. Collectively, these data identify a key developmental window when elevated microglial density in discrete basal ganglia nuclei may support circuit refinement and could increase susceptibility to inflammatory insults.
This study maps the time course and dynamics of microglial maturation in two mesolimbic nuclei, the ventral tegmental area (VTA) and the nucleus accumbens (NAc). We show that microglia are overproduced during the 2nd‐3rd postnatal week in mice and refined to adult levels through programmed cell death. This microglial overproduction was significantly larger in the NAc, revealing regional differences in microglial maturation that may impact circuit development and local vulnerability to damage.