TY - JOUR
T1 - Reduced SNAP-25 alters short-term plasticity at developing glutamatergic synapses
AU - Antonucci, Flavia
AU - Corradini, Irene
AU - Morini, Raffaella
AU - Fossati, Giuliana
AU - Menna, Elisabetta
AU - Pozzi, Davide
AU - Pacioni, Simone
AU - Verderio, Claudia
AU - Bacci, Alberto
AU - Matteoli, Michela
PY - 2013/6
Y1 - 2013/6
N2 - 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.
AB - 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.
KW - glutamatergic transmission
KW - short-term plasticity
KW - SNAP-25
UR - http://www.scopus.com/inward/record.url?scp=84879686362&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84879686362&partnerID=8YFLogxK
U2 - 10.1038/embor.2013.75
DO - 10.1038/embor.2013.75
M3 - Article
C2 - 23732542
AN - SCOPUS:84879686362
VL - 14
SP - 645
EP - 651
JO - EMBO Reports
JF - EMBO Reports
SN - 1469-221X
IS - 7
ER -