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Abstract

社会からの隔絶が不安を招く神経メカニズム、マウスで発見 : 引きこもりからの社会復帰へ向けた神経科学からのアプローチ. 京都大学プレスリリース. 2016-11-24.

Here, we show neuronal inactivation-induced presynaptic remodeling and involvement of the mammalian homolog of Diaphanous (mDia) and Rho-associated coiled-coil-containing kinase (ROCK), Rho-regulated modulators of actin and myosin, in this process. We find that social isolation induces inactivation of nucleus accumbens (NAc) neurons associated with elevated anxiety-like behavior, and that mDia in NAc neurons is essential in this process. Upon inactivation of cultured neurons, mDia induces circumferential actin filaments around the edge of the synaptic cleft, which contract the presynaptic terminals in a ROCK-dependent manner. Social isolation induces similar mDia-dependent presynaptic contraction at GABAergic synapses from NAc neurons in the ventral tegmental area (VTA) associated with reduced synaptic efficacy. Optogenetic stimulation of NAc neurons rescues the anxiety phenotype, and injection of a specific ROCK inhibitor, Y-27632, into the VTA reverses both presynaptic contraction and the behavioral phenotype. mDia-ROCK signaling thus mediates actin-dependent presynaptic remodeling in inactivated NAc neurons, which underlies synaptic plasticity in emotional behavioral responses.

Journal

  • Cell Reports

    Cell Reports 17(9), 2405-2417, 2016-11-22

    Elsevier B.V.

Codes

  • NII Article ID (NAID)
    120005954512
  • Text Lang
    ENG
  • Article Type
    journal article
  • ISSN
    2211-1247
  • Data Source
    IR 
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