期刊
EMBO REPORTS
卷 14, 期 7, 页码 645-651出版社
WILEY
DOI: 10.1038/embor.2013.75
关键词
SNAP-25; short-term plasticity; glutamatergic transmission
资金
- European Union Seventh Framework Programme [HEALTH-F2-2009-241498]
- Italian Ministry of Health [RF-2009-1545998]
- PRIN
- Telethon [GGP12115]
- Giovanni Armenise-Harvard Foundation: Career Development Award
- European Research Council (ERC) under the European Community's 7th Framework Programme (FP7)/ERC [200808]
- Italian Ministry of Research and Education program 'FIRB giovani' [RBFR10ZBYZ]
SNAP-25 is a key component of the synaptic-vesicle fusion machinery, involved in several psychiatric diseases including schizophrenia and ADHD. SNAP-25 protein expression is lower in different brain areas of schizophrenic patients and in ADHD mouse models. How the reduced expression of SNAP-25 alters the properties of synaptic transmission, leading to a pathological phenotype, is unknown. We show that, unexpectedly, halved SNAP-25 levels at 13-14 DIV not only fail to impair synaptic transmission but instead enhance evoked glutamatergic neurotransmission. This effect is possibly dependent on presynaptic voltage-gated calcium channel activity and is not accompanied by changes in spontaneous quantal events or in the pool of readily releasable synaptic vesicles. Notably, synapses of 13-14 DIV neurons with reduced SNAP-25 expression show paired-pulse depression as opposed to paired-pulse facilitation occurring in their wild-type counterparts. This phenotype disappears with synapse maturation. As alterations in short-term plasticity represent a new mechanism contributing to cognitive impairments in intellectual disabilities, our data provide mechanistic clues for neuronal circuit alterations in psychiatric diseases characterized by reduced expression of SNAP-25.
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