| First Author | Han M | Year | 2017 |
| Journal | Behav Brain Res | Volume | 321 |
| Pages | 176-184 | PubMed ID | 28063882 |
| Mgi Jnum | J:248702 | Mgi Id | MGI:5921298 |
| Doi | 10.1016/j.bbr.2016.12.042 | Citation | Han M, et al. (2017) Mice lacking GRIP1/2 show increased social interactions and enhanced phosphorylation at GluA2-S880. Behav Brain Res 321:176-184 |
| abstractText | Glutamate receptor interacting proteins 1 and 2 (GRIP1/2) play an important role in regulating synaptic trafficking of AMPA receptor 2/3 (GluA2/3) and synaptic strength. Gain-of-function GRIP1 mutations are implicated in social behavioral deficits in autism. To study mechanisms of Grip1/2-mediated AMPA signaling in the regulation of social behaviors, we performed social behavioral testing on neuron-specific Grip1/2-double knockout (DKO) and wild type (WT) mice that are matched for age, sex, and strain background. We determined the expression profile of key signaling proteins in AMPAR, mGluR, mTOR, and GABA pathways in frontal cortex, striatum, and cerebellum of DKO mice. Compared to WT mice, DKO mice show increased sociability in a modified three-chamber social behavioral test [mean+/-sem for interaction time in seconds; WT: 44.0+/-5.0; n=10; DKO: 81.0+/-9.0; n=9; two factor repeated measures ANOVA: F(1,37)=14.45; p<0.01 and planned t-test; p<0.01] and in a dyadic male-male social interaction test (mean+/-sem for total time in seconds: sniffing, WT-WT, 18.9+/-1.1; WT-DKO, 42.5+/-2.1; t-test: p<0.001; following, WT-WT, 7.7+/-0.72; WT-DKO,14.4+/-1.8; t-test: p<0.001). Immunoblot studies identified an increase in phosphorylation at GluA2-Serine 880 (GluA2-pS880) in frontal cortex (mean+/-sem; WT: 0.69+/-0.06, n=5; DKO: 0.96+/-0.06, n=6; t-test; p<0.05) and reduced GABAbeta3 expression in striatum (mean+/-sem; WT: 1.16+/-0.04, n=4; DKO: 0.95+/-0.06, n=4; t-test; p<0.05) in DKO mice. GluA2-S880 phosphorylation is known to regulate GluA2synaptic recycling, AMPA signaling strength and plasticity. GABAbeta3 has been implicated in the etiology and pathogenesis in autism. These data support an important role of Grip1/2-mediated AMPA signaling in regulating social behaviors and disturbance of glutamate- and GABA-signaling in specialized brain regions in autism-related social behavioral deficits. |
