CSF-1 controls cerebellar microglia and is required for motor function and social interaction

• Published in: The Journal of experimental medicine Vol. 216; no. 10; pp. 2265 - 2281
• Main Authors: Kana, Veronika, Desland, Fiona A, Casanova-Acebes, Maria, Ayata, Pinar, Badimon, Ana, Nabel, Elisa, Yamamuro, Kazuhiko, Sneeboer, Marjolein, Tan, I-Li, Flanigan, Meghan E, Rose, Samuel A, Chang, Christie, Leader, Andrew, Le Bourhis, Hortense, Sweet, Eric S, Tung, Navpreet, Wroblewska, Aleksandra, Lavin, Yonit, See, Peter, Baccarini, Alessia, Ginhoux, Florent, Chitu, Violeta, Stanley, E Richard, Russo, Scott J, Yue, Zhenyu, Brown, Brian D, Joyner, Alexandra L, De Witte, Lotje D, Morishita, Hirofumi, Schaefer, Anne, Merad, Miriam
• Format: Journal Article
• Language: English
• Published: United States Rockefeller University Press 07.10.2019
• Subjects: Animals; Behavior, Animal - physiology; Humans; Macrophage Colony-Stimulating Factor - genetics; Macrophage Colony-Stimulating Factor - metabolism; Mice; Mice, Transgenic; Microglia - metabolism; Motor Activity - physiology; Purkinje Cells - cytology; Purkinje Cells - metabolism; Receptor, Macrophage Colony-Stimulating Factor - genetics; Receptor, Macrophage Colony-Stimulating Factor - metabolism; Signal Transduction - physiology; Social Behavior
• ISSN: 1540-9538; 0022-1007; 1540-9538
• DOI: 10.1084/jem.20182037

Microglia, the brain resident macrophages, critically shape forebrain neuronal circuits. However, their precise function in the cerebellum is unknown. Here we show that human and mouse cerebellar microglia express a unique molecular program distinct from forebrain microglia. Cerebellar microglial identity was driven by the CSF-1R ligand CSF-1, independently of the alternate CSF-1R ligand, IL-34. Accordingly, CSF-1 depletion from Nestin cells led to severe depletion and transcriptional alterations of cerebellar microglia, while microglia in the forebrain remained intact. Strikingly, CSF-1 deficiency and alteration of cerebellar microglia were associated with reduced Purkinje cells, altered neuronal function, and defects in motor learning and social novelty interactions. These findings reveal a novel CSF-1-CSF-1R signaling-mediated mechanism that contributes to motor function and social behavior.