RT Journal Article SR Electronic T1 Disruption of Arp2/3 Results in Asymmetric Structural Plasticity of Dendritic Spines and Progressive Synaptic and Behavioral Abnormalities JF The Journal of Neuroscience JO J. Neurosci. FD Society for Neuroscience SP 6081 OP 6092 DO 10.1523/JNEUROSCI.0035-13.2013 VO 33 IS 14 A1 Kim, Il Hwan A1 Racz, Bence A1 Wang, Hong A1 Burianek, Lauren A1 Weinberg, Richard A1 Yasuda, Ryohei A1 Wetsel, William C. A1 Soderling, Scott H. YR 2013 UL http://www.jneurosci.org/content/33/14/6081.abstract AB 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.