Spine pruning drives antipsychotic-sensitive locomotion via circuit control of striatal dopamine

Il Hwan Kim, Mark A. Rossi, Dipendra K. Aryal, Bence Racz, Namsoo Kim, Akiyoshi Uezu, Wang Fan, William C. Wetsel, Richard J. Weinberg, Henry Yin, Scott H. Soderling

Research output: Contribution to journalArticle

51 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)883-891
Number of pages9
JournalNature Neuroscience
Volume18
Issue number6
DOIs
StatePublished - Jun 28 2015

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Corpus Striatum
Locomotion
Antipsychotic Agents
Dopamine
Dendritic Spines
Spine
Pathology
Psychiatry
Optogenetics
Actin-Related Protein 2-3 Complex
Psychomotor Agitation
Pyramidal Cells
Mesencephalon
Cytoskeleton
Drive

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)

Cite this

Kim, I. H., Rossi, M. A., Aryal, D. K., Racz, B., Kim, N., Uezu, A., ... Soderling, S. H. (2015). Spine pruning drives antipsychotic-sensitive locomotion via circuit control of striatal dopamine. Nature Neuroscience, 18(6), 883-891. https://doi.org/10.1038/nn.4015

Spine pruning drives antipsychotic-sensitive locomotion via circuit control of striatal dopamine. / Kim, Il Hwan; Rossi, Mark A.; Aryal, Dipendra K.; Racz, Bence; Kim, Namsoo; Uezu, Akiyoshi; Fan, Wang; Wetsel, William C.; Weinberg, Richard J.; Yin, Henry; Soderling, Scott H.

In: Nature Neuroscience, Vol. 18, No. 6, 28.06.2015, p. 883-891.

Research output: Contribution to journalArticle

Kim, IH, Rossi, MA, Aryal, DK, Racz, B, Kim, N, Uezu, A, Fan, W, Wetsel, WC, Weinberg, RJ, Yin, H & Soderling, SH 2015, 'Spine pruning drives antipsychotic-sensitive locomotion via circuit control of striatal dopamine', Nature Neuroscience, vol. 18, no. 6, pp. 883-891. https://doi.org/10.1038/nn.4015
Kim, Il Hwan ; Rossi, Mark A. ; Aryal, Dipendra K. ; Racz, Bence ; Kim, Namsoo ; Uezu, Akiyoshi ; Fan, Wang ; Wetsel, William C. ; Weinberg, Richard J. ; Yin, Henry ; Soderling, Scott H. / Spine pruning drives antipsychotic-sensitive locomotion via circuit control of striatal dopamine. In: Nature Neuroscience. 2015 ; Vol. 18, No. 6. pp. 883-891.
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