Reduced SNAP-25 alters short-term plasticity at developing glutamatergic synapses

Flavia Antonucci, Irene Corradini, Raffaella Morini, Giuliana Fossati, Elisabetta Menna, Davide Pozzi, Simone Pacioni, Claudia Verderio, Alberto Bacci, Michela Matteoli

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)645-651
Number of pages7
JournalEMBO Reports
Volume14
Issue number7
DOIs
Publication statusPublished - Jun 2013

Keywords

  • glutamatergic transmission
  • short-term plasticity
  • SNAP-25

ASJC Scopus subject areas

  • Genetics
  • Molecular Biology
  • Biochemistry

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