Vesicular Glutamate Transporter Expression Level Affects Synaptic Vesicle Release Probability at Hippocampal Synapses in Culture

The vesicular glutamate transporter (VGLUT) plays an essential role in synaptic transmission by filling vesicles with glutamate. At mammalian synapses, VGLUT expression level determines the amount of glutamate packaged into vesicles, and the specific paralog of VGLUT expressed affects the release probability. In this study, we investigate whether there is a link between the number of VGLUTs on vesicles and release probability. We used a combination of electrophysiology and imaging techniques in cultured mouse hippocampal neurons where the VGLUT expression level has been severely altered. We found that vesicles with drastically reduced VGLUT expression were released with a lower probability. This deficit in release could only be rescued by a functional transporter, suggesting that the transport function, and not the molecular interactions, of the protein affects vesicle release. Based on these data, we propose a novel means of presynaptic vesicle release regulation-the intravesicular glutamate fill state of the vesicle.