PT - JOURNAL ARTICLE AU - Eric W. Salter AU - Gang Lei AU - Sun-Lim Choi AU - Liam T. Ralph AU - Lijia Zhang AU - Fuzi Jin AU - Ashish Kadia AU - Junhui Wang AU - John Georgiou AU - Graham L. Collingridge TI - Complement C3-dependent glutamatergic synapse elimination in the developing hippocampus is region- and synapse-specific AID - 10.1101/2020.05.20.106930 DP - 2020 Jan 01 TA - bioRxiv PG - 2020.05.20.106930 4099 - http://biorxiv.org/content/early/2020/05/22/2020.05.20.106930.short 4100 - http://biorxiv.org/content/early/2020/05/22/2020.05.20.106930.full AB - The complement cascade is an innate immune pathway that, in addition to host defense against pathogens, actively maintains tissue homeostasis. Complement is necessary for synaptic pruning during development and drives aberrant synapse loss in a number of neurodegenerative disorders that affect the hippocampus. However, the physiological function of complement in hippocampal synapse development is unknown. To address this, we investigated C3−/− mice at P16-18. We found that VGLUT2+ synapses were increased in the CA1 stratum lacunosum moleculare (SLM) and dentate gyrus molecular layer (DGML) of C3−/− mice compared to wildtype. Conversely, VGLUT1+ synapses, inhibitory synapses and myelin were not affected in the CA1 stratum radiatum (SR), SLM or DGML of C3−/− mice. Finally, we found that there was a decrease in microglial phagocytic activity only in VGLUT2+ regions and this correlated with the amount of VGLUT2+ synapses. Our study elucidates a role of the complement cascade in regulating hippocampus synapse number with exceptional specificity for VGLUT2-containing synapses during development.Competing Interest StatementThe authors have declared no competing interest.