Reduced SNAP‐25 alters short‐term plasticity at developing glutamatergic synapses |
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Authors: | Flavia Antonucci Irene Corradini Raffaella Morini Giuliana Fossati Elisabetta Menna Davide Pozzi Simone Pacioni Claudia Verderio Alberto Bacci Michela Matteoli |
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Institution: | 1. Department of Biotechnology and Translational Medicine, University of Milan, , 20129 Milano;2. CNR Institute of Neuroscience, , 20129 Milano;3. Fondazione Filarete viale Ortles 22/4, , 20139 Milano;4. Istituto Clinico Humanitas, IRCCS, , Rozzano, 20089 Milano;5. Fondazione IRCCS Don Gnocchi, , 20162 Milano;6. European Brain Research Institute (EBRI), , Roma, Italy;7. Centre National de la Recherche Scientifique, Unité Mixte de Recherche 7225, Institut du Cerveau et de la Moelle épinière (ICM), , 75013 Paris, France |
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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. |
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Keywords: | SNAP‐25 short‐term plasticity glutamatergic transmission |
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