Microglia contribute to the postnatal development of cortical somatostatin-positive inhibitory cells and to whisker-evoked cortical activity

Lorenzo Gesuita; Anna Cavaccini; Ali Özgür Argunsah; Emilia Favuzzi; Leena Ali Ibrahim; Tevye Jason Stachniak; Martina De Gennaro; Sebastian Utz; Melanie Greter; Theofanis Karayannis

doi:10.1016/j.celrep.2022.111209

Microglia contribute to the postnatal development of cortical somatostatin-positive inhibitory cells and to whisker-evoked cortical activity

Lorenzo Gesuita, Anna Cavaccini, Ali Özgür Argunsah, Emilia Favuzzi, Leena Ali Ibrahim, Tevye Jason Stachniak, Martina De Gennaro, Sebastian Utz, Melanie Greter, Theofanis Karayannis

Research output: Contribution to journal › Article › peer-review

11 Scopus citations

Abstract

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.

Original language	English (US)
Pages (from-to)	111209
Journal	Cell Reports
Volume	40
Issue number	7
DOIs	https://doi.org/10.1016/j.celrep.2022.111209
State	Published - Aug 16 2022

Bibliographical note

KAUST 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

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10.1016/j.celrep.2022.111209

https://repository.kaust.edu.sa/bitstream/10754/680432/1/1-s2.0-S2211124722010269-main.pdf

Cite this

Gesuita, L., Cavaccini, A., Argunsah, A. Ö., Favuzzi, E., Ibrahim, L. A., Stachniak, T. J., De Gennaro, M., Utz, S., Greter, M., & Karayannis, T. (2022). Microglia contribute to the postnatal development of cortical somatostatin-positive inhibitory cells and to whisker-evoked cortical activity. Cell Reports, 40(7), 111209. https://doi.org/10.1016/j.celrep.2022.111209

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title = "Microglia contribute to the postnatal development of cortical somatostatin-positive inhibitory cells and to whisker-evoked cortical activity",

abstract = "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.",

author = "Lorenzo Gesuita and Anna Cavaccini and Argunsah, {Ali {\"O}zg{\"u}r} and Emilia Favuzzi and Ibrahim, {Leena Ali} and Stachniak, {Tevye Jason} and {De Gennaro}, Martina and Sebastian Utz and Melanie Greter and Theofanis Karayannis",

note = "KAUST 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{\textquoteright}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).",

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AU - Argunsah, Ali Özgür

AU - Favuzzi, Emilia

AU - Ibrahim, Leena Ali

AU - Stachniak, Tevye Jason

AU - De Gennaro, Martina

AU - Utz, Sebastian

AU - Greter, Melanie

AU - Karayannis, Theofanis

N1 - KAUST 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).

PY - 2022/8/16

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N2 - 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.

AB - 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.

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SN - 2211-1247

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JO - Cell Reports

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ER -

Microglia contribute to the postnatal development of cortical somatostatin-positive inhibitory cells and to whisker-evoked cortical activity

Abstract

Bibliographical note

ASJC Scopus subject areas

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