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Author Notes:

Correspondence and requests for materials should be addressed to B.D.T. (email: trappb@ccf.org).

B.D.T. conceived and supervised the project. Z.C., W.J., J.T.G. and B.D.T. designed the study.

Z.C., W.J., W.H., Z.C.G. and R.D. performed the experiments.

Z.C., W.J., G.J.K., H.-J.P., J.T.G., W.H., J.C., R.D. and B.D.T. analysed the data. Z.C., W.J., J.T.G. and B.D.T. wrote the manuscript.

We thank Dr Christopher L. Nelson for scientific discussion and editing assistance; Dr Dolores Hambardzumyan for advice; Drs Olga Nicole Kokiko-Cochran and Yu-Shang Lee for assisting with fluid percussion injury; and Dr Amir Avishai, Mrs Nan Avishai, Ms Jennifer Powers, Ms Emily Benson, Mr Ken Farabaugh and Ms Chinonyelum Erokwu for technical support.

Subjects:

Research Funding:

This investigation is supported by the Bakken Heart and Brain Institute and the Nancy Davis Foundation. Z.C. is supported by a fellowship from the American Epilepsy Foundation and received a scholarship from the Multiple Sclerosis Society of Canada. W.J. received a postdoctoral fellowship from the National Multiple Sclerosis Society (FG1711-A-1).

Keywords:

  • Science & Technology
  • Multidisciplinary Sciences
  • Science & Technology - Other Topics
  • CEREBELLAR GRANULE CELLS
  • NMDA RECEPTOR
  • IN-VIVO
  • ACTIVATION
  • CNS
  • TERMINALS
  • DEATH
  • LIPOPOLYSACCHARIDE
  • INFLAMMATION
  • EXPRESSION

Microglial displacement of inhibitory synapses provides neuroprotection in the adult brain

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Journal Title:

Nature Communications

Volume:

Volume 5, Number 1

Publisher:

, Pages 4486-4486

Type of Work:

Article | Final Publisher PDF

Abstract:

Microglia actively survey the brain microenvironment and play essential roles in sculpting synaptic connections during brain development. While microglial functions in the adult brain are less clear, activated microglia can closely appose neuronal cell bodies and displace axosomatic presynaptic terminals. Microglia-mediated stripping of presynaptic terminals is considered neuroprotective, but the cellular and molecular mechanisms are poorly defined. Using 3D electron microscopy, we demonstrate that activated microglia displace inhibitory presynaptic terminals from cortical neurons in adult mice. Electrophysiological recordings further establish that the reduction in inhibitory GABAergic synapses increased synchronized firing of cortical neurons in γ-frequency band. Increased neuronal activity results in the calcium-mediated activation of CaM kinase IV, phosphorylation of CREB, increased expression of antiapoptotic and neurotrophic molecules and reduced apoptosis of cortical neurons following injury. These results indicate that activated microglia can protect the adult brain by migrating to inhibitory synapses and displacing them from cortical neurons.

Copyright information:

© 2014 Macmillan Publishers Limited. All rights reserved.

This is an Open Access work distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/).
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