GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE327nnn/GSE327095/primaryOK200OtherMus musculusOtherhttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE327095GEOGSEfalseC1q and immunoglobulins mediate activity-dependent synapse loss in the adult brain.C1q, the initiator of the classical complement cascade, mediates synaptic elimination during development and disease, yet the triggers for C1q deposition on synapses in the adult brain remain unclear. Using in vivo chemogenetics, we demonstrate that neuronal hyperactivity acts as a trigger for region-specific C1q deposition and synapse loss in the adult hippocampus of wild-type mice; importantly, C1qa deficiency abolishes this activity-dependent synapse remodeling. Conversely, suppressing perforant pathway hyperactivity in a mouse model of Alzheimer’s disease lowers local Aβ levels, reduces C1q deposition, and partially rescues synapse loss. Further, using spatial transcriptomics, live cell tracking, super-resolution microscopy and other molecular and cellular tools, we report a surprising role for B lymphocyte lineage antibody-secreting cells in the activity-dependent C1q deposition and synapse loss in the non-diseased adult hippocampus. Overall, our work suggests a functional link between neuronal hyperactivity and C1q-mediated synapse loss in the adult brain and introduces immunoglobulins as players in this process.2026/04/10GSE327095GSM9648224GSM964822524247327095Mus musculus