title: Reduced SNAP-25 alters short-term plasticity at developing glutamatergic synapses.
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.
authors.affiliation: Department of Biotechnology and Translational Medicine, University of Milan, Via Vanvitelli 32, 20129 Milano, Italy.
authors.forename: Flavia
authors.initials: F
authors.lastname: Antonucci
authors.forename: Irene
authors.initials: I
authors.lastname: Corradini
authors.forename: Raffaella
authors.initials: R
authors.lastname: Morini
authors.forename: Giuliana
authors.initials: G
authors.lastname: Fossati
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Menna
authors.forename: Davide
authors.initials: D
authors.lastname: Pozzi
authors.forename: Simone
authors.initials: S
authors.lastname: Pacioni
authors.forename: Claudia
authors.initials: C
authors.lastname: Verderio
authors.forename: Alberto
authors.initials: A
authors.lastname: Bacci
authors.forename: Michela
authors.initials: M
authors.lastname: Matteoli
mesh_terms: D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000235:genetics / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D020868:Gene Silencing; D018698:Glutamic Acid / Q000378:metabolism* / Q000494:pharmacology; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects; D006801:Humans; D051379:Mice; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology*; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D061251:Primary Cell Culture; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D051381:Rats; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*; D013572:Synaptic Vesicles / Q000187:drug effects / Q000502:physiology; D050825:Synaptosomal-Associated Protein 25 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism / Q000494:pharmacology
chemical_list: D015220:Calcium Channels; D034741:RNA, Small Interfering; C494209:Snap25 protein, mouse; C494210:Snap25 protein, rat; D050825:Synaptosomal-Associated Protein 25; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; D002118:Calcium