Microglia play a key role in shaping the formation and refinement of the excitatory network of the brain. However, less is known about whether and how they organize the development of distinct inhibitory networks. We find that microglia are essential for the proper development of somatostatin-positive (SST+) cell synapses during the second postnatal week. We further identify a pair of molecules that act antagonistically to one another in the organization of SST+ cell axonal elaboration. Whereas CX3CL1 acts to suppress axonal growth and complexity, CXCL12 promotes it. Assessing the functional importance of microglia in the development of cortical activity, we find that a whisker stimulation paradigm that drives SST+ cell activation leads to reduced cortical spiking in brains depleted of microglia. Collectively, our data demonstrate an important role of microglia in regulating the development of SST+ cell output early in life.
Bibliographical noteKAUST Repository Item: Exported on 2022-09-14
Acknowledgements: We are grateful to Gord Fishell for his precious feedback and for his valuable comments on previous versions of this manuscript. We would also like to thank all members of the Karayannis laboratory for stimulating discussions. Imaging was performed with equipment maintained by the Center for Microscopy and Image Analysis, University of Zurich. L.G. was supported by the Forschungskredit of the University of Zurich, grant no. FK-20-029. E.F. was supported by the Charles A. King Trust Postdoctoral Research Fellowship Program, Bank of America, N.A., Co-Trustees. L.A.I. was supported by FY19 Hearst Fellowship. Research in the M.G. lab was supported by the European Research Council under the European Union’s Horizon 2020 Research and Innovation Program (ERC, 819229) and the Swiss National Science Foundation (SNSF, BSSGI0_155832). Research in the T.K. lab was supported by grants from the European Research Council (ERC, 679175) and the Swiss National Science Foundation (SNSF, 31003A_170037).
ASJC Scopus subject areas
- General Biochemistry, Genetics and Molecular Biology