RT Journal Article SR Electronic T1 Microglial activation results in neuron-type-specific increase in mPFC GABAergic transmission and abnormal behavior in mice JF bioRxiv FD Cold Spring Harbor Laboratory SP 2020.06.13.149906 DO 10.1101/2020.06.13.149906 A1 Binliang Tang A1 Jinxiang Jiang A1 Lei Wang A1 Afzal Misrani A1 Qingwei Huo A1 Yuanyuan Han A1 Cheng Long A1 Li Yang YR 2020 UL http://biorxiv.org/content/early/2020/06/14/2020.06.13.149906.abstract AB 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.Competing Interest StatementThe authors have declared no competing interest.