Disruption of Arp2/3 results in asymmetric structural plasticity of dendritic spines and progressive synaptic and behavioral abnormalities

Il Hwan Kim, Bence Racz, Hong Wang, Lauren Burianek, Richard Weinberg, Ryohei Yasuda, William C. Wetsel, Scott H. Soderling

Research output: Contribution to journalArticle

82 Citations (Scopus)

Abstract

Despite evidence for a strong genetic contribution to several major psychiatric disorders, individual candidate genes account for only a small fraction of these disorders, leading to the suggestion that multigenetic pathways may be involved. Several known genetic risk factors for psychiatric disease are related to the regulation of actin polymerization, which plays a key role in synaptic plasticity. To gain insight into and test the possible pathogenetic role of this pathway, we designed a conditional knock-out of the Arp2/3 complex, a conserved final output for actin signaling pathways that orchestrates de novo actin polymerization. Here we report that postnatal loss of the Arp2/3 subunit ArpC3 in forebrain excitatory neurons leads to an asymmetric structural plasticity of dendritic spines, followed by a progressive loss of spine synapses. This progression of synaptic deficits corresponds with an evolution of distinct cognitive, psychomotor, and social disturbances as the mice age. Together, these results point to the dysfunction of actin signaling, specifically that which converges to regulate Arp2/3, as an important cellular pathway that may contribute to the etiology of complex psychiatric disorders.

Original languageEnglish (US)
Pages (from-to)6081-6092
Number of pages12
JournalJournal of Neuroscience
Volume33
Issue number14
DOIs
StatePublished - Apr 3 2013

Fingerprint

Dendritic Spines
Actins
Psychiatry
Polymerization
Actin-Related Protein 2-3 Complex
Neuronal Plasticity
Prosencephalon
Synapses
Spine
Neurons
Genes

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)

Cite this

Disruption of Arp2/3 results in asymmetric structural plasticity of dendritic spines and progressive synaptic and behavioral abnormalities. / Kim, Il Hwan; Racz, Bence; Wang, Hong; Burianek, Lauren; Weinberg, Richard; Yasuda, Ryohei; Wetsel, William C.; Soderling, Scott H.

In: Journal of Neuroscience, Vol. 33, No. 14, 03.04.2013, p. 6081-6092.

Research output: Contribution to journalArticle

Kim, Il Hwan ; Racz, Bence ; Wang, Hong ; Burianek, Lauren ; Weinberg, Richard ; Yasuda, Ryohei ; Wetsel, William C. ; Soderling, Scott H. / Disruption of Arp2/3 results in asymmetric structural plasticity of dendritic spines and progressive synaptic and behavioral abnormalities. In: Journal of Neuroscience. 2013 ; Vol. 33, No. 14. pp. 6081-6092.
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