RT Journal Article
SR Electronic
T1 Microglia complement signaling promotes neuronal elimination and normal brain functional connectivity
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2021.03.31.437118
DO 10.1101/2021.03.31.437118
A1 Senthilkumar Deivasigamani
A1 Mariya Timotey Miteva
A1 Silvia Natale
A1 Daniel Gutierrez-Barragan
A1 Bernadette Basilico
A1 Silvia Di Angelantonio
A1 Constantin Pape
A1 Giulia Bolasco
A1 Alberto Galbusera
A1 Alessandro Gozzi
A1 Davide Ragozzino
A1 Cornelius T. Gross
YR 2021
UL http://biorxiv.org/content/early/2021/04/02/2021.03.31.437118.abstract
AB Complement signaling is thought to serve as an opsonization signal to promote the phagocytosis of synapses by microglia. However, while its role in synaptic remodeling has been demonstrated in the retino-thalamic system, it remains unclear whether complement signaling mediates synaptic pruning in the brain more generally. Here we show that mice lacking the complement 3 receptor (C3r), the major microglia complement receptor, fail to show a deficit in either synaptic pruning or axon elimination in the developing mouse cortex. Instead, mice lacking C3r show a deficit in the perinatal elimination of neurons, both in the retina as well as in the cortex, a deficit that is associated with increased cortical thickness and enhanced functional connectivity in these regions in adulthood. These data demonstrate a preferential role for complement in promoting neuronal elimination in the developing brain and argue for a reconsideration of the role of complement in synaptic pruning.Competing Interest StatementThe authors have declared no competing interest.