Incomplete removal of extracellular glutamate controls synaptic transmission and integration at a cerebellar synapse

Timothy S. Balmer, Carolina Borges-Merjane, Laurence O. Trussell

Research output: Contribution to journalArticlepeer-review

Abstract

Synapses of glutamatergic mossy fibers 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 mossy fiber 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.

Original languageEnglish (US)
Article numbere63819
Pages (from-to)1-62
Number of pages62
JournaleLife
Volume10
DOIs
StatePublished - Feb 2021
Externally publishedYes

ASJC Scopus subject areas

  • Neuroscience(all)
  • Immunology and Microbiology(all)
  • Biochemistry, Genetics and Molecular Biology(all)

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