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

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-positi...

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Published in:Cell reports (Cambridge) 2022-08, Vol.40 (7), p.111209-111209, Article 111209
Main Authors: Gesuita, Lorenzo, Cavaccini, Anna, Argunsah, Ali Özgür, Favuzzi, Emilia, Ibrahim, Leena Ali, Stachniak, Tevye Jason, De Gennaro, Martina, Utz, Sebastian, Greter, Melanie, Karayannis, Theofanis
Format: Article
Language:English
Subjects:
cerebral cortex
development
inhibitory synapses
interneurons
microglia
somatostatin
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Summary: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. [Display omitted] •Microglia depletion leads to an increase of SST+ cell synapses during development•Microglia control SST+ cell axonal development through CX3CL1 and CXCL12•Microglia depletion reduces sensory-driven cortical activation early postnatally Gesuita et al. demonstrate that microglia contribute to cortical somatostatin-positive (SST+) inhibitory cell development. Early postnatal microglia depletion increases SST+ synapse density and reduces sensory-driven activation of the barrel cortex. Moreover, the chemokines CX3CL1 and CXCL12 control SST+ cell axonal development through microglia-dependent mechanisms.
ISSN:2211-1247
2211-1247
DOI:10.1016/j.celrep.2022.111209