TY - JOUR TI - Phagocyte-mediated synapse removal in cortical neuroinflammation is promoted by local calcium accumulation AU - Jafari, Mehrnoosh AU - Schumacher, Adrian-Minh AU - Snaidero, Nicolas AU - Ullrich Gavilanes, Emily M. AU - Neziraj, Tradite AU - Kocsis-Jutka, Virág AU - Engels, Daniel AU - Jürgens, Tanja AU - Wagner, Ingrid AU - Weidinger, Juan Daniel Flórez AU - Schmidt, Stephanie S. AU - Beltrán, Eduardo AU - Hagan, Nellwyn AU - Woodworth, Lisa AU - Ofengeim, Dimitry AU - Gans, Joseph AU - Wolf, Fred AU - Kreutzfeldt, Mario AU - Portugues, Ruben AU - Merkler, Doron AU - Misgeld, Thomas AU - Kerschensteiner, Martin T2 - Nature Neuroscience AB - Cortical pathology contributes to chronic cognitive impairment of patients suffering from the neuroinflammatory disease multiple sclerosis (MS). How such gray matter inflammation affects neuronal structure and function is not well understood. In the present study, we use functional and structural in vivo imaging in a mouse model of cortical MS to demonstrate that bouts of cortical inflammation disrupt cortical circuit activity coincident with a widespread, but transient, loss of dendritic spines. Spines destined for removal show local calcium accumulations and are subsequently removed by invading macrophages or activated microglia. Targeting phagocyte activation with a new antagonist of the colony-stimulating factor 1 receptor prevents cortical synapse loss. Overall, our study identifies synapse loss as a key pathological feature of inflammatory gray matter lesions that is amenable to immunomodulatory therapy. DA - 2021/01/25/ PY - 2021 DO - 10.1038/s41593-020-00780-7 DP - www.nature.com SP - 1 EP - 13 LA - en SN - 1546-1726 UR - https://www.nature.com/articles/s41593-020-00780-7 Y2 - 2021/01/25/21:19:15 ER -