Early detonation by sprouted mossy fibers enables aberrant dentate network activity

William D. Hendricks, Gary L. Westbrook, Eric Schnell

Research output: Contribution to journalArticle

Abstract

In temporal lobe epilepsy, sprouting of hippocampal mossy fiber axons onto dentate granule cell dendrites creates a recurrent excitatory network. However, unlike mossy fibers projecting to CA3, sprouted mossy fiber synapses depress upon repetitive activation. Thus, despite their proximal location, relatively large presynaptic terminals, and ability to excite target neurons, the impact of sprouted mossy fiber synapses on hippocampal hyperexcitability is unclear. We find that despite their short-term depression, single episodes of sprouted mossy fiber activation in hippocampal slices initiated bursts of recurrent polysynaptic excitation. Consistent with a contribution to network hyperexcitability, optogenetic activation of sprouted mossy fibers reliably triggered action potential firing in postsynaptic dentate granule cells after single light pulses. This pattern resulted in a shift in network recruitment dynamics to an “early detonation” mode and an increased probability of release compared with mossy fiber synapses in CA3. A lack of tonic adenosine-mediated inhibition contributed to the higher probability of glutamate release, thus facilitating reverberant circuit activity.

Original languageEnglish (US)
Pages (from-to)10994-10999
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume166
Issue number22
DOIs
StatePublished - May 28 2019

Keywords

  • Adenosine
  • Epilepsy
  • Mossy fiber
  • Sprouting

ASJC Scopus subject areas

  • General

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