Synaptic Pruning of Murine Adult-born Neurons by Microglia Depends on Phosphatidylserine

Overview

Journal J Exp Med

Specialties Allergy & Immunology
General Medicine

Date 2022 Mar 17

PMID 35297954

Authors

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

Affiliations

Soon will be listed here.

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.

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