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bioRxiv · 10.1101/353730

Microglia-triggered hyperexcitability in the cerebellum depresses animal behaviors

Yamamoto, M.·Kim, M.·Imai, H.·Ohtsuki, G.
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Abstract

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- (TNF-) 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- 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--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.

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Yamamoto, M., Kim, M., Imai, H., Ohtsuki, G.. 2018-06-22. Microglia-triggered hyperexcitability in the cerebellum depresses animal behaviors. https://doi.org/10.1101/353730

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