Open AccessAbnormal neurotransmission in mice lacking synaptic vesicle protein 2A (SV2A)
Author(s) -
Kelly M. Crowder,
Jane M. Gunther,
Theresa A. Jones,
Brian D. Hale,
Hai Zhuan Zhang,
Michael R. Peterson,
Richard H. Scheller,
Charles Chavkin,
Sandra M. Bajjalieh
Publication year - 1999
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.96.26.15268
Subject(s) - neurotransmission , synaptic vesicle , exocytosis , biology , synaptic fatigue , munc 18 , synapsin , synapse , synaptic augmentation , neuroscience , inhibitory postsynaptic potential , neurotransmitter , hippocampus , secretion , endocrinology , vesicle , central nervous system , biochemistry , receptor , membrane
Synaptic vesicle protein 2 (SV2) is a membrane glycoprotein common to all synaptic and endocrine vesicles. Unlike many proteins involved in synaptic exocytosis, SV2 has no homolog in yeast, indicating that it performs a function unique to secretion in higher eukaryotes. Although the structure and protein interactions of SV2 suggest multiple possible functions, its role in synaptic events remains unknown. To explore the function of SV2 in anin vivo context, we generated mice that do not express the primary SV2 isoform, SV2A, by using targeted gene disruption. Animals homozygous for the SV2A gene disruption appear normal at birth. However, they fail to grow, experience severe seizures, and die within 3 weeks, suggesting multiple neural and endocrine deficits. Electrophysiological studies of spontaneous inhibitory neurotransmission in the CA3 region of the hippocampus revealed that loss of SV2A leads to a reduction in action potential-dependent γ-aminobutyric acid (GABA)ergic neurotransmission. In contrast, action potential-independent neurotransmission was normal. Analyses of synapse ultrastructure suggest that altered neurotransmission is not caused by changes in synapse density or morphology. These findings demonstrate that SV2A is an essential protein and implicate it in the control of exocytosis.