Synaptic pruning of murine adult-born neurons by microglia depends on phosphatidylserine

Mechanisms for synaptic pruning of adult-born neurons remain unknown. In this study, Kurematsu et al. demonstrate that phosphatidylserine is involved in microglial spine pruning and functional maturation of adult-born neurons in the olfactory bulb and hippocampus. New neurons, continuously added in the adult olfactory bulb (OB) and hippocampus, are involved in information processing in neural circuits. Here, we show that synaptic pruning of adult-born neurons by microglia depends on phosphatidylserine (PS), whose exposure on dendritic spines is inversely correlated with their input activity. To study the role of PS in spine pruning by microglia in vivo, we developed an inducible transgenic mouse line, in which the exposed PS is masked by a dominant-negative form of milk fat globule-EGF-factor 8 (MFG-E8), MFG-E8(D89E). In this transgenic mouse, the spine pruning of adult-born neurons by microglia is impaired in the OB and hippocampus. Furthermore, the electrophysiological properties of these adult-born neurons are altered in MFG-E8(D89E) mice. These data suggest that PS is involved in the microglial spine pruning and the functional maturation of adult-born neurons. The MFG-E8(D89E)-based genetic approach shown in this study has broad applications for understanding the biology of PS-mediated phagocytosis in vivo.

Automated summary

This study demonstrates the involvement of phosphatidylserine (PS) in the synaptic pruning and functional maturation of adult-born neurons in the olfactory bulb and hippocampus. Using an inducible transgenic mouse model, the researchers found that impaired microglial spine pruning and altered electrophysiological properties of adult-born neurons occurred when PS exposure was masked by a dominant-negative form of milk fat globule-EGF-factor 8 (MFG-E8). These findings highlight the significance of PS in microglial pruning and the maturation of adult-born neurons.