@article{a0e865d4ba714dcabc9726ff5cd53b3e,
title = "Spine pruning drives antipsychotic-sensitive locomotion via circuit control of striatal dopamine",
abstract = "Psychiatric and neurodevelopmental disorders may arise from anomalies in long-range neuronal connectivity downstream of pathologies in dendritic spines. However, the mechanisms that may link spine pathology to circuit abnormalities relevant to atypical behavior remain unknown. Using a mouse model to conditionally disrupt a critical regulator of the dendritic spine cytoskeleton, the actin-related protein 2/3 complex (Arp2/3), we report here a molecular mechanism that unexpectedly reveals the inter-relationship of progressive spine pruning, elevated frontal cortical excitation of pyramidal neurons and striatal hyperdopaminergia in a cortical-to-midbrain circuit abnormality. The main symptomatic manifestations of this circuit abnormality are psychomotor agitation and stereotypical behaviors, which are relieved by antipsychotics. Moreover, this antipsychotic-responsive locomotion can be mimicked in wild-type mice by optogenetic activation of this circuit. Collectively these results reveal molecular and neural-circuit mechanisms, illustrating how diverse pathologies may converge to drive behaviors relevant to psychiatric disorders.",
author = "Kim, {Il Hwan} and Rossi, {Mark A.} and Aryal, {Dipendra K.} and Bence Racz and Namsoo Kim and Akiyoshi Uezu and Wang Fan and Wetsel, {William C.} and Weinberg, {Richard J.} and Henry Yin and Soderling, {Scott H.}",
note = "Funding Information: We thank M. Caron, B. Hogan and C. Eroglu for critical reading and comments. We also thank K. Kobayashi (Fukushima Medical University, Japan) for providing the FuGB2 viral vector, K. Sakurai (Duke University) for providing the hSyn-Cre lentiviral vector, and R. Rodriguiz and E. Spence for behavioral technical support. This work was supported by the following grants: US National Institutes of Health (NIH) MH103374 and NS059957 (S.H.S.), NIH NS077986 (F.W.), AA021074 (H.Y.), NS039444 (R.J.W.) and MH082441 (W.C.W.). M.R. is supported by a US National Research Foundation fellowship and B.R. is supported by the J{\'a}nos B{\'o}lyai Research Fellowship from the Hungarian Academy of Sciences, by the Hungarian Scientific Research Fund (OTKA, grant K83830) and by the Szent Istv{\'a}n University, Faculty of Veterinary Science (Research Faculty Grant 2014). Some of the experiments were conducted with equipment/software purchased with a North Carolina Biotechnology Center grant (W.C.W.). Publisher Copyright: {\textcopyright} 2015 Nature America, Inc.",
year = "2015",
month = jun,
day = "28",
doi = "10.1038/nn.4015",
language = "English (US)",
volume = "18",
pages = "883--891",
journal = "Nature Neuroscience",
issn = "1097-6256",
publisher = "Nature Publishing Group",
number = "6",
}