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

EMBO reports 2013 Jul

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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.

Citation

Flavia Antonucci, Irene Corradini, Raffaella Morini, Giuliana Fossati, Elisabetta Menna, Davide Pozzi, Simone Pacioni, Claudia Verderio, Alberto Bacci, Michela Matteoli. Reduced SNAP-25 alters short-term plasticity at developing glutamatergic synapses. EMBO reports. 2013 Jul;14(7):645-51