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Although only 30\u201340% of carriers of the mutation show overt motor symptoms, most experience enhanced excitability of the central nervous system. The cellular mechanism responsible for this change in excitability is not well understood. Here we show the effects of the \u0394<jats:italic>E<\/jats:italic>\u2010torsinA mutation on miniature neurotransmitter release from neurons. Neurotransmitter release was characterized in cultured hippocampal neurons obtained from wild\u2010type, heterozygous, and homozygous \u0394<jats:italic>E<\/jats:italic>\u2010torsinA knock\u2010in mice using two approaches. In the first approach, patch\u2010clamp electrophysiology was used to record glutamate\u2010mediated miniature excitatory postsynaptic currents (mEPSCs) in the presence of the Na<jats:sup>+<\/jats:sup> channel blocker tetrodotoxin (TTX) and absence of GABA<jats:sub>A<\/jats:sub> receptor antagonists. The intervals between mEPSC events were significantly shorter in neurons obtained from the mutant mice than in those obtained from wild\u2010type mice. In the second approach, the miniature exocytosis of synaptic vesicles was detected by imaging the unstimulated release of FM dye from the nerve terminals in the presence of TTX. Cumulative FM dye release was higher in neurons obtained from the mutant mice than in those obtained from wild\u2010type mice. The number of glutamatergic nerve terminals was also assessed, and we found that this number was unchanged in heterozygous relative to wild\u2010type neurons, but slightly increased in homozygous neurons. Notably, in both heterozygous and homozygous neurons, the unitary synaptic charge during each mEPSC event was unchanged. Overall, our results suggest more frequent miniature glutamate release in neurons with \u0394E\u2010torsinA mutations. This change may be one of the underlying mechanisms by which the excitability of the central nervous system is enhanced in the context of DYT1 dystonia. Moreover, qualitative differences between heterozygous and homozygous neurons with respect to certain synaptic properties indicate that the abnormalities observed in homozygotes may reflect more than a simple gene dosage effect. Synapse 66:807\u2013822, 2012. \u00a9 2012 Wiley Periodicals, Inc.<\/jats:p>","DOI":"10.1002\/syn.21571","type":"journal-article","created":{"date-parts":[[2012,5,15]],"date-time":"2012-05-15T13:58:41Z","timestamp":1337090321000},"page":"807-822","source":"Crossref","is-referenced-by-count":28,"title":["Miniature release events of glutamate from hippocampal neurons are influenced by the dystonia\u2010associated protein torsinA"],"prefix":"10.1002","volume":"66","author":[{"given":"Yasuhiro","family":"Kakazu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin\u2010Young","family":"Koh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sadahiro","family":"Iwabuchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pedro","family":"Gonzalez\u2010Alegre","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"N. 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