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Updated: Sep 30, 2025
Isolation of Cortical Microglia with Preserved Immunophenotype and Functionality From Murine Neonates
Published on: January 30, 2014
Synaptic pruning of murine adult-born neurons by microglia depends on phosphatidylserine
Chihiro Kurematsu1, Masato Sawada1,2, Masaki Ohmuraya3
1Department of Developmental and Regenerative Neurobiology, Institute of Brain Science, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
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.
Insights
Microglia prune synapses on new neurons via phosphatidylserine (PS) exposure. Masking PS in adult mice impairs this pruning, affecting neuronal function and maturation in the olfactory bulb and hippocampus.
Area of Science:
- Neuroscience
- Cell Biology
- Immunology
Background:
- Adult neurogenesis occurs in the olfactory bulb (OB) and hippocampus, contributing to neural circuit function.
- Microglia are key immune cells in the brain involved in synaptic pruning.
- Phosphatidylserine (PS) exposure on cellular structures signals for phagocytosis.
Purpose of the Study:
- To investigate the role of phosphatidylserine (PS) in microglial-mediated synaptic pruning of adult-born neurons in vivo.
- To develop a genetic tool to manipulate PS exposure and study its effects on neuronal development.
Main Methods:
- Development of an inducible transgenic mouse line expressing a dominant-negative form of MFG-E8 (MFG-E8D89E) to mask exposed PS.
- In vivo assessment of microglial spine pruning in the OB and hippocampus of MFG-E8D89E mice.
- Electrophysiological recordings to evaluate the properties of adult-born neurons.
Main Results:
- Masking PS with MFG-E8D89E significantly impaired microglial spine pruning of adult-born neurons in both the OB and hippocampus.
- Adult-born neurons in MFG-E8D89E mice exhibited altered electrophysiological properties.
- PS exposure is identified as a crucial signal for microglial-mediated synaptic pruning.
Conclusions:
- Phosphatidylserine (PS) plays a critical role in microglial spine pruning of adult-born neurons.
- PS-mediated pruning is essential for the functional maturation of adult-born neurons.
- The MFG-E8D89E mouse model provides a valuable tool for studying PS-mediated phagocytosis in vivo.
