Short-Term Depression of Sprouted Mossy Fiber Synapses from Adult-Born Granule Cells

The Journal of Neuroscience : the Official Journal of the Society for Neuroscience
William D HendricksEric Schnell

Abstract

Epileptic seizures potently modulate hippocampal adult neurogenesis, and adult-born dentate granule cells contribute to the pathologic retrograde sprouting of mossy fiber axons, both hallmarks of temporal lobe epilepsy. The characteristics of these sprouted synapses, however, have been largely unexplored, and the specific contribution of adult-born granule cells to functional mossy fiber sprouting is unknown, primarily due to technical barriers in isolating sprouted mossy fiber synapses for analysis. Here, we used DcxCreERT2 transgenic mice to permanently pulse-label age-defined cohorts of granule cells born either before or after pilocarpine-induced status epilepticus (SE). Using optogenetics, we demonstrate that adult-born granule cells born before SE form functional recurrent monosynaptic excitatory connections with other granule cells. Surprisingly, however, although healthy mossy fiber synapses in CA3 are well characterized "detonator" synapses that potently drive postsynaptic cell firing through their profound frequency-dependent facilitation, sprouted mossy fiber synapses from adult-born cells exhibited profound frequency-dependent depression, despite possessing some of the morphological hallmarks of mossy fiber terminal...Continue Reading

Citations

May 16, 2019·Proceedings of the National Academy of Sciences of the United States of America·William D HendricksEric Schnell
Dec 12, 2019·F1000Research·Cristina V DieniLinda Overstreet-Wadiche
Jan 6, 2018·Npj Regenerative Medicine·Sofia Grade, Magdalena Götz
Dec 18, 2018·Frontiers in Neurology·Clarissa F CavarsanLuciene Covolan
Sep 29, 2019·Epilepsy Currents·Mark Beenhakker, Matthew Ritger
Nov 25, 2019·Epilepsy & Behavior : E&B·Victor Rodrigues SantosOlagide Wagner de Castro

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