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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Neural Circuits | doi: 10.3389/fncir.2019.00055

Microglia Regulate Pruning of Specialized Synapses in the Auditory Brainstem

  • 1Department of Neurobiology and Behavior, University of California, Irvine, United States
  • 2Vollum Institute, Oregon Health & Science University, United States
  • 3Garvan Institute of Medical Research, Australia
  • 4St Vincent's Clinical School, Faculty of Medicine, University of New South Wales, Australia
  • 5University of California, Irvine, United States

The assembly of uniquely organized sound localization circuits in the brainstem requires precise developmental mechanisms. Glial cells have been shown to shape synaptic connections in the retinogeniculate system during development, but their contributions to specialized auditory synapses have not been identified. Here we investigated the role of microglia in auditory brainstem circuit assembly, focusing on the formation and pruning of the calyx of Held in the medial nucleus of the trapezoid body (MNTB). Microglia were pharmacologically depleted in mice early in development using subcutaneous injections of an inhibitor of colony stimulating factor 1 receptor, which is essential for microglia survival. Brainstems were examined prior to and just after hearing onset, at postnatal days (P) 8 and P13, respectively. We found that at P13 there were significantly more polyinnervated MNTB neurons when microglia were depleted, consistent with a defect in pruning. Expression of glial fibrillary acidic protein (GFAP), a mature astrocyte marker that normally appears in the MNTB late in development, was significantly decreased in microglia-depleted mice at P13, suggesting a delay in astrocyte maturation. Our results demonstrate that monoinnervation of MNTB neurons by the calyx of Held is significantly disrupted or delayed in the absence of microglia. This finding may reflect a direct role for microglia in synaptic pruning. A secondary role for microglia may be in the maturation of astrocytes in MNTB. These findings highlight the significant function of glia in pruning during calyx of Held development.

Keywords: Microglia, calyx of held, MNTB, pruning, CSF1R inhibitors, depletion

Received: 17 May 2019; Accepted: 30 Jul 2019.

Copyright: © 2019 Milinkeviciute, Henningfield, Muniak, Chokr, Green and Cramer. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Prof. Karina S. Cramer, Department of Neurobiology and Behavior, University of California, Irvine, Irvine, 92697, California, United States, cramerk@uci.edu