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: Flavia Antonucci, Irene Corradini, Raffaella Morini, Giuliana Fossati, Elisabetta Menna, Davide Pozzi, Simone Pacioni, Claudia Verderio, Alberto Bacci, Michela Matteoli
• Journal: EMBO reports (EMBO Rep) Vol. 14 Issue 7 Pg. 645-51 (Jul 2013) ISSN: 1469-3178 [Electronic] England
• PMID: 23732542 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Calcium Channels
• RNA, Small Interfering
• Snap25 protein, mouse
• Snap25 protein, rat
• Synaptosomal-Associated Protein 25
• Glutamic Acid
• gamma-Aminobutyric Acid
• Calcium

Topics

• Action Potentials (drug effects, physiology)
• Animals
• Calcium (metabolism)
• Calcium Channels (genetics, metabolism)
• Gene Expression Regulation, Developmental
• Gene Silencing
• Glutamic Acid (metabolism, pharmacology)
• Hippocampus (cytology, drug effects)
• Humans
• Mice
• Neuronal Plasticity (drug effects, physiology)
• Neurons (cytology, drug effects, physiology)
• Primary Cell Culture
• RNA, Small Interfering (genetics, metabolism)
• Rats
• Synaptic Transmission (drug effects, physiology)
• Synaptic Vesicles (drug effects, physiology)
• Synaptosomal-Associated Protein 25 (antagonists & inhibitors, genetics, metabolism)
• gamma-Aminobutyric Acid (metabolism, pharmacology)