Dark Microglia Are Abundant in Normal Postnatal Development, where they Remodel Synapses via Phagocytosis and Trogocytosis, and Are Dependent on TREM2
Haley A. VecchiarelliiD, Kanchan BishtiD, Kaushik P. SharmaiD, Sammy Weiser NovakiD, Marianela Evelyn TraettaiD, Monica Emili Garcia‐SeguraiD, Marie‐Kim St‐PierreiD, Julie C. SavageiD, Cory M. WillisiD, Katherine PicardiD, Maude Bordeleau, Nathalie VernouxiD, Mohammadparsa KhakpouriD, Rishika Garg, Sophia M. LoeweniD, Colin J. MurrayiD, Yelena Y. GrinbergiD, Joel V. FaustinoiD, Torin HalvorsoniD, Victor Z. LauiD, Stefano PluchinoiD, Zinaida S. VexleriD, Monica J. CarsoniD, Uri ManoriD, Luca Peruzzotti‐JamettiiD, Marie‐Ève TremblayiD
Abstract
This study examined dark microglia--a state linked to central nervous system pathology and neurodegeneration--during postnatal development in the mouse ventral hippocampus, finding that dark microglia interact with blood vessels and synapses and perform trogocytosis of pre-synaptic axon terminals. Furthermore, we found that dark microglia in development notably expressed C-type lectin domain family 7 member A (CLEC7a), lipoprotein lipase (LPL) and triggering receptor expressed on myeloid cells 2 (TREM2) and required TREM2, differently from other microglia, suggesting a link between their role in remodeling during development and central nervous system pathology. Together, these results point towards a previously under-appreciated role for dark microglia in synaptic pruning and plasticity during normal postnatal development.
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