Potential molecular mechanisms for decreased synaptic glutamate release in dysbindin-1 mutant mice

SCHIZOPHRENIA RESEARCH

卷:146

Article

Saggu, Shalini¹  Cannon, Tyrone D.^2,3  Jentsch, J. David⁴  Lavin, Antonieta¹ 

[1] Med Univ S Carolina, Dept Neurosci, Charleston, SC 29425 USA

[2] Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA 90024 USA

[3] Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA

[4] Univ Calif Los Angeles, Dept Human Genet, Los Angeles, CA USA

关键词: Prefrontal cortex;    Calcium;    Dysbindin;    Synapsin;    Synaptotagmin;    Synaptic vesicles;   

DOI  :  10.1016/j.schres.2013.01.037

来源: Elsevier

【 摘 要 】

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 Ca2+ 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 [Ca2+](i), expression of L-and N-type Ca2+ channels and several proteins involved in synaptic vesicle trafficking and priming. Our results provide new insights into the mechanisms of action of dysbindin-1. (C) 2013 Elsevier B.V. All rights reserved.

【 授权许可】

Free