mDia and ROCK Mediate Actin-Dependent Presynaptic Remodeling Regulating Synaptic Efficacy and Anxiety
抄録
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.
収録刊行物
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- Cell Reports
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Cell Reports 17 (9), 2405-2417, 2016-11
Cell Press
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詳細情報 詳細情報について
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- CRID
- 1050282677602893312
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- NII論文ID
- 120005868496
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- HANDLE
- 2241/00145138
- 2433/217361
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- ISSN
- 22111247
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- 本文言語コード
- en
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- 資料種別
- journal article
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- データソース種別
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