RT Journal Article
SR Electronic
T1 Presynaptic G-Protein-Coupled Receptors Regulate Synaptic Cleft Glutamate via Transient Vesicle Fusion
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 5857
OP 5868
DO 10.1523/JNEUROSCI.1160-07.2007
VO 27
IS 22
A1 Eric J. Schwartz
A1 Trillium Blackmer
A1 Tatyana Gerachshenko
A1 Simon Alford
YR 2007
UL http://www.jneurosci.org/content/27/22/5857.abstract
AB When synaptic vesicles fuse with the plasma membrane, they may completely collapse or fuse transiently. Transiently fusing vesicles remain structurally intact and therefore have been proposed to represent a form of rapid vesicle recycling. However, the impact of a transient synaptic vesicle fusion event on neurotransmitter release, and therefore on synaptic transmission, has yet to be determined. Recently, the molecular mechanism by which a serotonergic presynaptic G-protein-coupled receptor (GPCR) regulates synaptic vesicle fusion and inhibits synaptic transmission was identified. By making paired electrophysiological recordings in the presence and absence of low-affinity antagonists, we now demonstrate that activation of this presynaptic GPCR lowers the peak synaptic cleft glutamate concentration independently of the probability of vesicle fusion. Furthermore, this change in cleft glutamate concentration differentially inhibits synaptic NMDA and AMPA receptor-mediated currents. We conclude that a presynaptic GPCR regulates the profile of glutamate in the synaptic cleft through altering the mechanism of vesicle fusion leading to qualitative as well as quantitative changes in neural signaling.