article published yes Timothy S Balmer author Carolina Borges Merjane author 4305C450-F248-11E8-B48F-1D18A9856A870000-0003-0005-401X Laurence O Trussell author PeJo department Synapses of glutamatergic mossy fibers (MFs) onto cerebellar unipolar brush cells (UBCs) generate slow excitatory (ON) or inhibitory (OFF) postsynaptic responses dependent on the complement of glutamate receptors expressed on the UBC’s large dendritic brush. Using mouse brain slice recording and computational modeling of synaptic transmission, we found that substantial glutamate is maintained in the UBC synaptic cleft, sufficient to modify spontaneous firing in OFF UBCs and tonically desensitize AMPARs of ON UBCs. The source of this ambient glutamate was spontaneous, spike-independent exocytosis from the MF terminal, and its level was dependent on activity of glutamate transporters EAAT1–2. Increasing levels of ambient glutamate shifted the polarity of evoked synaptic responses in ON UBCs and altered the phase of responses to in vivo-like synaptic activity. Unlike classical fast synapses, receptors at the UBC synapse are virtually always exposed to a significant level of glutamate, which varies in a graded manner during transmission. https://research-explorer.ista.ac.at/download/15273/15307/2021_eLife_Balmer.pdf application/pdfno eLife Sciences Publications2021 eng General Immunology and MicrobiologyGeneral BiochemistryGenetics and Molecular BiologyGeneral MedicineGeneral Neuroscience 2050-084X 3361603610.7554/elife.63819 10 Balmer, T. S., Borges Merjane, C., &#38; Trussell, L. O. (2021). Incomplete removal of extracellular glutamate controls synaptic transmission and integration at a cerebellar synapse. <i>ELife</i>. eLife Sciences Publications. <a href="https://doi.org/10.7554/elife.63819">https://doi.org/10.7554/elife.63819</a> Balmer, Timothy S, Carolina Borges Merjane, and Laurence O Trussell. “Incomplete Removal of Extracellular Glutamate Controls Synaptic Transmission and Integration at a Cerebellar Synapse.” <i>ELife</i>. eLife Sciences Publications, 2021. <a href="https://doi.org/10.7554/elife.63819">https://doi.org/10.7554/elife.63819</a>. T.S. Balmer, C. Borges Merjane, L.O. Trussell, ELife 10 (2021). Balmer TS, Borges Merjane C, Trussell LO. 2021. Incomplete removal of extracellular glutamate controls synaptic transmission and integration at a cerebellar synapse. eLife. 10, e63819. Balmer TS, Borges Merjane C, Trussell LO. Incomplete removal of extracellular glutamate controls synaptic transmission and integration at a cerebellar synapse. <i>eLife</i>. 2021;10. doi:<a href="https://doi.org/10.7554/elife.63819">10.7554/elife.63819</a> Balmer, Timothy S., et al. “Incomplete Removal of Extracellular Glutamate Controls Synaptic Transmission and Integration at a Cerebellar Synapse.” <i>ELife</i>, vol. 10, e63819, eLife Sciences Publications, 2021, doi:<a href="https://doi.org/10.7554/elife.63819">10.7554/elife.63819</a>. T. S. Balmer, C. Borges Merjane, and L. O. Trussell, “Incomplete removal of extracellular glutamate controls synaptic transmission and integration at a cerebellar synapse,” <i>eLife</i>, vol. 10. eLife Sciences Publications, 2021. 152732024-04-03T07:58:11Z2024-04-09T11:15:01Z