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.
Reduced SNAP-25 alters short-term plasticity at developing glutamatergic synapses / F. Antonucci, I. Corradini, R. Morini, G. Fossati, E. Menna, D. Pozzi, S. Pacioni, C. Verderio, A. Bacci, M. Matteoli. - In: EMBO REPORTS. - ISSN 1469-221X. - 14:7(2013), pp. 645-651.
|Titolo:||Reduced SNAP-25 alters short-term plasticity at developing glutamatergic synapses|
ANTONUCCI, FLAVIA (Primo)
CORRADINI, IRENE (Secondo)
BACCI, ALBERTO LUIGI (Penultimo)
MATTEOLI, MICHELA (Ultimo)
|Parole Chiave:||glutamatergic transmission; short-term plasticity; SNAP-25|
|Settore Scientifico Disciplinare:||Settore BIO/14 - Farmacologia|
|Data di pubblicazione:||2013|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1038/embor.2013.75|
|Appare nelle tipologie:||01 - Articolo su periodico|