Abstract
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.
Original language | English (US) |
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Pages (from-to) | 254-263 |
Number of pages | 10 |
Journal | Schizophrenia Research |
Volume | 146 |
Issue number | 1-3 |
DOIs | |
State | Published - May 2013 |
Externally published | Yes |
Keywords
- Calcium
- Dysbindin
- Prefrontal cortex
- Synapsin
- Synaptic vesicles
- Synaptotagmin
ASJC Scopus subject areas
- Psychiatry and Mental health
- Biological Psychiatry