Review Article

Fractalkine Signaling and Microglia Functions in the Developing Brain

Figure 2

Fractalkine/CX3CR1 signaling modulates synaptic pruning by microglia during postnatal development. (a) Microglial cells remove presynaptic elements by synaptic pruning at P5 in the retinogeniculate system. (a1) Low magnification electronic microscopy of microglia. Asterisks denote the nucleus and the cytoplasm is pseudocolored green. Scale bar = 1 μm. (a2) Magnified regions of (a1) (white box) demonstrating membrane-bound elements engulfed by microglia. Arrows designate elements containing presynaptic machinery (40 nm vesicles). The arrowhead designates engulfed material resembling juxtaposed postsynaptic elements. Scale bar = 100 nm. Adapted from [53]. (b) A transient increase in dendritic spine density was observed in CX3CR1 deficient (KO/KO) mice when compared with WT (+/+) littermates during the second postnatal week ( < 0.0001). This transient increase in dendritic spines number could result of a transient deficit of synaptic pruning. (c) Quantification of microglia nuclei in the CA1 stratum radiatum from the hippocampus revealed a transient decrease in microglia density in CX3CR1 deficient mice at P8, P15, and P28 compared with control littermates < 0.005). This decrease in microglia number in KO mice suggests a transient delayed microglia recruitment which can explain the transient deficit of synaptic pruning. ((b) and (c)) Adapted from [47].