TY - JOUR TI - Incomplete removal of extracellular glutamate controls synaptic transmission and integration at a cerebellar synapse AU - Balmer, Timothy S AU - Borges-Merjane, Carolina AU - Trussell, Laurence O A2 - Toth, Katalin A2 - Huguenard, John R A2 - Marty, Alain VL - 10 PY - 2021 DA - 2021/02/22 SP - e63819 C1 - eLife 2021;10:e63819 DO - 10.7554/eLife.63819 UR - https://doi.org/10.7554/eLife.63819 AB - 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. KW - glutamate receptors KW - mossy fiber KW - vestibular KW - desensitization KW - cerebellum JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -