TY - JOUR T1 - Synaptic and Vesicular Coexistence of VGLUT and VGAT in Selected Excitatory and Inhibitory Synapses JF - The Journal of Neuroscience JO - J. Neurosci. SP - 7634 LP - 7645 DO - 10.1523/JNEUROSCI.0141-10.2010 VL - 30 IS - 22 AU - Johannes-Friedrich Zander AU - Agnieszka Münster-Wandowski AU - Irene Brunk AU - Ingrid Pahner AU - Gisela Gómez-Lira AU - Uwe Heinemann AU - Rafael Gutiérrez AU - Gregor Laube AU - Gudrun Ahnert-Hilger Y1 - 2010/06/02 UR - http://www.jneurosci.org/content/30/22/7634.abstract N2 - The segregation between vesicular glutamate and GABA storage and release forms the molecular foundation between excitatory and inhibitory neurons and guarantees the precise function of neuronal networks. Using immunoisolation of synaptic vesicles, we now show that VGLUT2 and VGAT, and also VGLUT1 and VGLUT2, coexist in a sizeable pool of vesicles. VGAT immunoisolates transport glutamate in addition to GABA. Furthermore, VGLUT activity enhances uptake of GABA and monoamines. Postembedding immunogold double labeling revealed that VGLUT1, VGLUT2, and VGAT coexist in mossy fiber terminals of the hippocampal CA3 area. Similarly, cerebellar mossy fiber terminals harbor VGLUT1, VGLUT2, and VGAT, while parallel and climbing fiber terminals exclusively contain VGLUT1 or VGLUT2, respectively. VGLUT2 was also observed in cerebellar GABAergic basket cells terminals. We conclude that the synaptic coexistence of vesicular glutamate and GABA transporters allows for corelease of both glutamate and GABA from selected nerve terminals, which may prevent systemic overexcitability by downregulating synaptic activity. Furthermore, our data suggest that VGLUT enhances transmitter storage in nonglutamatergic neurons. Thus, synaptic and vesicular coexistence of VGLUT and VGAT is more widespread than previously anticipated, putatively influencing fine-tuning and control of synaptic plasticity. ER -