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

Shalini Saggu, Tyrone D. Cannon, J. David Jentsch, Antonieta Lavin

Research output: Contribution to journalArticlepeer-review

23 Scopus citations


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 languageEnglish (US)
Pages (from-to)254-263
Number of pages10
JournalSchizophrenia Research
Issue number1-3
StatePublished - May 2013
Externally publishedYes


  • Calcium
  • Dysbindin
  • Prefrontal cortex
  • Synapsin
  • Synaptic vesicles
  • Synaptotagmin

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Biological Psychiatry


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