Synaptic pruning of murine adult-born neurons by microglia depends on phosphatidylserine
Chihiro Kurematsu, Masato Sawada, Masaki Ohmuraya, Motoki Tanaka, Kazuya Kuboyama, Takashi Ogino, Mami Matsumoto, Hisashi Oishi, Hiroyuki Inada, Yuri Ishido, Yukina Sakakibara, Huy Bang Nguyen, Truc Quynh Thai, Shinichi Kohsaka, Nobuhiko Ohno, Maki Yamada, Masato Asai, Masahiro Sokabe, Junichi Nabekura, Kenichi Asano, Masato Tanaka, Kazunobu Sawamoto
Abstract
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-E8D89E. 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-E8D89E mice. These data suggest that PS is involved in the microglial spine pruning and the functional maturation of adult-born neurons. The MFG-E8D89E-based genetic approach shown in this study has broad applications for understanding the biology of PS-mediated phagocytosis in vivo.