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Title: Microglia-Triggered Plasticity of Intrinsic Excitability Modulates Psychomotor Behaviors in Acute Cerebellar Inflammation
Authors: Yamamoto, Masamichi
Kim, Minsoo
Imai, Hirohiko
Itakura, Yamato
Ohtsuki, Gen
Author's alias: 山本, 正道
キム, ミンス
今井, 宏彦
板倉, 大和
大槻, 元
Keywords: Purkinje cells
intrinsic plasticity
dendritic excitability
synaptic currents
inflammatory cytokines
functional connectivity
psychomotor behaviors
Issue Date: 10-Sep-2019
Publisher: Elsevier BV
Journal title: Cell Reports
Volume: 28
Issue: 11
Start page: 2923
End page: 2938.e8
Abstract: Cerebellar dysfunction relates to various psychiatric disorders, including autism spectrum and depressive disorders. However, the physiological aspect is less advanced. Here, we investigate the immune-triggered hyperexcitability in the cerebellum on a wider scope. Activated microglia via exposure to bacterial endotoxin lipopolysaccharide or heat-killed Gram-negative bacteria induce a potentiation of the intrinsic excitability in Purkinje neurons, which is suppressed by microglia-activity inhibitor and microglia depletion. An inflammatory cytokine, tumor necrosis factor alpha (TNF-α), released from microglia via toll-like receptor 4, triggers this plasticity. Our two-photon FRET ATP imaging shows an increase in ATP concentration following endotoxin exposure. Both TNF-α and ATP secretion facilitate synaptic transmission. Region-specific inflammation in the cerebellum in vivo shows depression- and autistic-like behaviors. Furthermore, both TNF-α inhibition and microglia depletion revert such behavioral abnormality. Resting-state functional MRI reveals overconnectivity between the inflamed cerebellum and the prefrontal neocortical regions. Thus, immune activity in the cerebellum induces neuronal hyperexcitability and disruption of psychomotor behaviors in animals.
Description: 小脳炎症時の神経活動の過興奮によって鬱様症状が起こる仕組みを解明. 京都大学プレスリリース. 2019-09-11.
An overactive cerebellum causes issues across the brain. 京都大学プレスリリース. 2019-09-12.
Rights: © 2019 The Author(s). This is an open access article under the CC BY-NC-ND license (
DOI(Published Version): 10.1016/j.celrep.2019.07.078
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