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Microglia are dispensable for experience-dependent refinement of mouse visual circuitry

Abstract

To test the hypothesized crucial role of microglia in the developmental refinement of neural circuitry, we depleted microglia from mice of both sexes with PLX5622 and examined the experience-dependent maturation of visual circuitry and function. We assessed retinal function, receptive field tuning of visual cortex neurons, acuity and experience-dependent plasticity. None of these measurements detectibly differed in the absence of microglia, challenging the role of microglia in sculpting neural circuits.

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Fig. 1: Visual signaling in retina of mice without microglia.
Fig. 2: Retinogeniculate segregation in LGN, neuronal tuning properties in V1 and acuity of mice without microglia.
Fig. 3: OD plasticity of mice without microglia.

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Data availability

The deposited data listed in the Methods table were deposited to Mendeley data at https://data.mendeley.com/datasets/4x96trx9tv/1.

Code availability

No new code was generated by this study.

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Acknowledgements

This work was supported by a Karl Kirchgessner award (to B.G.B.), a grant from the E. Matilda Ziegler Foundation for the Blind (to S.W.M. and B.G.B.), grants from the NIH (EY035138, to A.W.M.; EY028188, to B.G.B.) and a Jewish Heritage Fund for Excellence Research Enhancement Grant (A.W.M.). The funders had no role in study design, data collection and analysis, decision to publish or preparation of the paper.

Author information

Authors and Affiliations

Authors

Contributions

B.G.B., A.W.M. and T.C.B. conceptualized and designed the study. T.C.B., E.C.C., C.A.A., D.K.O., S.W.M., B.G.B. and A.W.M. performed experiments and analyzed the data. T.C.B., B.G.B. and A.W.M. wrote the paper.

Corresponding author

Correspondence to Aaron W. McGee.

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The authors declare no competing interests.

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Nature Neuroscience thanks Michael Stryker and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

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Extended data

Extended Data Fig. 1 Timeline of PLX treatment and representative coronal images of control and PLX-treated brains.

(a) The PLX treatment was initiated at P14. Experiments to examine the refinement of visual circuitry and plasticity began after P24 as indicated. (b) Representative images of coronal sections of brains from control mice and PLX-treated mice at P18, P21, P28 stained with antibodies directed at Iba-1.

Supplementary information

Reporting Summary

Supplementary Video 1

Calcium imaging of V1 in control mouse at neuronal resolution. Images were collected at 15.5 fps. Images are presented at 100 fps (~7× speed). The video is downsampled to 480p.

Supplementary Video 2

Calcium imaging of V1 in PLX-treated mouse at neuronal resolution. Images were collected at 15.5 fps. Images are presented at 100 fps (~7× speed). The video is downsampled to 480p.

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Brown, T.C., Crouse, E.C., Attaway, C.A. et al. Microglia are dispensable for experience-dependent refinement of mouse visual circuitry. Nat Neurosci 27, 1462–1467 (2024). https://doi.org/10.1038/s41593-024-01706-3

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