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bioRxiv · 10.1101/2020.06.13.149906

Microglial activation results in neuron-type-specific increase in mPFC GABAergic transmission and abnormal behavior in mice

Yang, L.·Tang, B.·Jiang, J.·Wang, L.·Misrani, A.·Huo, Q.·Han, Y.·Long, C.
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Abstract

Neuroinflammation and synaptic dysfunction are two early symptoms of most neurological diseases. However, the mechanisms underlying microglia-associated neuroinflammation in the regulation of synaptic activity remain obscure. We report here that acute neuroinflammation induced by a single-dose proinflammatory cytokine inducer, lipopolysaccharide (LPS), results in enhanced inhibitory postsynaptic currents (IPSCs) of glutamatergic neurons, upregulated levels of GABAAR subunits, glutamine synthetase (GS) and vGAT, and downregulated BDNF and pTrkB levels, due to enhanced activation of microglia in the medial prefrontal cortex (mPFC). Blockage of microglial activation by minocycline ameliorated LPS-induced aberrant mIPSCs and associated aberrant protein expression and behavior. Exogenous application of BDNF prior to LPS challenge also ameliorated LPS-induced abnormal mIPSCs. Thus, this study elucidates a critical role for microglia in the neurobiology of GABAergic synaptic dysfunction induced by neuroinflammation, revealing a novel GABAergic signaling pathway that might be targeted therapeutically to treat neuroinflammation-induced abnormal synaptic activity and associated aberrant behavior.

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Yang, L., Tang, B., Jiang, J., Wang, L., Misrani, A., Huo, Q., Han, Y., Long, C.. 2020-06-14. Microglial activation results in neuron-type-specific increase in mPFC GABAergic transmission and abnormal behavior in mice. https://doi.org/10.1101/2020.06.13.149906

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