| First Author | Hines RM | Year | 2013 |
| Journal | Proc Natl Acad Sci U S A | Volume | 110 |
| Issue | 41 | Pages | 16628-33 |
| PubMed ID | 24043839 | Mgi Jnum | J:202327 |
| Mgi Id | MGI:5518491 | Doi | 10.1073/pnas.1308706110 |
| Citation | Hines RM, et al. (2013) Disrupting the clustering of GABAA receptor alpha2 subunits in the frontal cortex leads to reduced gamma-power and cognitive deficits. Proc Natl Acad Sci U S A 110(41):16628-33 |
| abstractText | In schizophrenia, cognitive dysfunction is highly predictive of poor patient outcomes and is not responsive to current medications. Postmortem studies have suggested that cognitive deficits in schizophrenia are correlated with modifications in the number and size of inhibitory synapses. To test if these modifications lead to cognitive deficits, we have created a dominant-negative virus [adeno-associated (AAV)-DN1] that disrupts the clustering of gamma-aminobutyric acid type A receptors (GABAARs) at postsynaptic inhibitory specializations. When injected into the frontal cortex of mice, AAV-DN1 impairs GABAAR alpha2 subunit and GABA transporter 1 (GAT-1) clustering, but increases GABAAR alpha1 subunit clustering on the perisomatic region, with no influence on axon-initial segment clustering. Mice expressing AAV-DN1 have prepulse inhibition deficits and impairments in working memory. Significantly, these behavioral deficits are paralleled by a reduction in electroencephalography gamma-power. Collectively, our study provides functional evidence revealing that GABAergic synapses in the prefrontal cortex directly contribute to cognition and gamma-power. |
