2024-03-28T23:33:39Z
https://tsukuba.repo.nii.ac.jp/oai
oai:tsukuba.repo.nii.ac.jp:00040189
2023-07-12T06:22:57Z
2770:2579
2770:2581
3:62:5298:5294
mDia and ROCK Mediate Actin-Dependent Presynaptic Remodeling Regulating Synaptic Efficacy and Anxiety
Deguchi, Yuichi
Harada, Masaya
Shinohara, Ryota
ラザルス, ミハエル
ラザルス, ミハエル
LAZARUS, Michael
Cherasse, Yoan
裏出 , 良博
Urade, Yoshihiro
Yamada, Daisuke
Sekiguchi, Masayuki
Watanabe, Dai
Furuyashiki, Tomoyuki
Narumiya, Shuh
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 article
Cell Press
2016-11
application/pdf
Cell Reports
9
17
2405
2417
2211-1247
https://tsukuba.repo.nii.ac.jp/record/40189/files/CR_17-9.pdf
eng
27880913
https://doi.org/10.1016/j.celrep.2016.10.088
(c) 2016 The Authors
This is an open access article under the CC BY-NC-ND license ( http://creativecommons.org /licenses/by-nc-nd/4.0/ ).
open access