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.
Synaptic pruning of murine adult-born neurons by microglia depends on phosphatidylserine
Disclosures: The authors declare no competing interests exist.
- Award Id(s): 21gm1210007
- Award Id(s): 26250019,26640046,15H01217,15H01384,17H01392,17H05750,17H05512,19H04757,19H04785,18KK0213,20H05700,26830014,18K14823,21K06395,16H06280
- Award Id(s): 217,227,209,222,19-222,19-234,20-226,20-247,21-224,21-243
- Views Icon Views
- Share Icon Share
- Search Site
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 K. Yamada, Masato Asai, Masahiro Sokabe, Junichi Nabekura, Kenichi Asano, Masato Tanaka, Kazunobu Sawamoto; Synaptic pruning of murine adult-born neurons by microglia depends on phosphatidylserine. J Exp Med 4 April 2022; 219 (4): e20202304. doi: https://doi.org/10.1084/jem.20202304
Download citation file: