| First Author | Saggu S | Year | 2013 |
| Journal | Schizophr Res | Volume | 146 |
| Issue | 1-3 | Pages | 254-63 |
| PubMed ID | 23473812 | Mgi Jnum | J:197997 |
| Mgi Id | MGI:5495073 | Doi | 10.1016/j.schres.2013.01.037 |
| Citation | Saggu S, et al. (2013) Potential molecular mechanisms for decreased synaptic glutamate release in dysbindin-1 mutant mice. Schizophr Res 146(1-3):254-63 |
| abstractText | Behavioral genetic studies of humans have associated variation in the DTNBP1 gene with schizophrenia and its cognitive deficit phenotypes. The protein encoded by DTNBP1, dysbindin-1, is expressed in forebrain neurons where it interacts with proteins mediating vesicular trafficking and exocytosis. It has been shown that loss of dysbindin-1 results in a decrease in glutamate release in the prefrontal cortex; however the mechanisms underlying this decrease are not fully understood. In order to investigate this question, we evaluated dysbindin-1 null mutant mice, using electrophysiological recordings of prefrontal cortical neurons, imaging studies of vesicles, calcium dynamics and Western blot measures of synaptic proteins and Ca(2+) channels. Dysbindin-1 null mice showed a decrease in the ready releasable pool of synaptic vesicles, decreases in quantal size, decreases in the probability of release and deficits in the rate of endo- and exocytosis compared with wild-type controls. Moreover, the dysbindin-1 null mice show decreases in the [Ca(2+)]i,expression of L- and N-type Ca(2+)channels and several proteins involved in synaptic vesicle trafficking and priming. Our results provide new insights into the mechanisms of action of dysbindin-1. |
