TY - JOUR T1 - Microglia-triggered hyperexcitability in the cerebellum depresses animal behaviors JF - bioRxiv DO - 10.1101/353730 SP - 353730 AU - Masamichi Yamamoto AU - Minsoo Kim AU - Hirohiko Imai AU - Gen Ohtsuki Y1 - 2018/01/01 UR - http://biorxiv.org/content/early/2018/06/22/353730.abstract N2 - Clinical studies have suggested that cerebellar dysfunction is involved in various psychiatric disorders, including autism spectrum disorders, dyslexia, and depressive disorders. However, the physiological aspect is less-advanced. Here, we comprehensively investigated the immune-triggered excitability plasticity in the cerebellum. Activated microglia (MG) via exposure to bacterial endotoxin lipopolysaccharide or heat-killed Gram-negative bacteria induced a potentiation of the excitability of Purkinje neurons, which was suppressed by MG-activity inhibitor and MG-depletion. An inflammatory cytokine, tumor necrosis factor-α (TNF-α) released from MG triggered this plasticity. While our new two-photon FRET ATP-imaging showed an increase in ATP concentration following endotoxin exposure, both TNF-α and ATP secretion facilitated synaptic transmission. Inflammation in the cerebellar anterior vermis in vivo immobilized animals, and reduced sociability. Such abulia-like behavioral impairments were reverted by TNF-α-inhibition and MG-depletion. Resting-state functional MRI revealed overconnectivity between the inflamed cerebellum and prefrontal neocortical regions, which may underlie the psychomotor depressiveness in animals. ER -