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Early detonation by sprouted mossy fibers enables aberrant dentate network activity.
- Source :
-
Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2019 May 28; Vol. 116 (22), pp. 10994-10999. Date of Electronic Publication: 2019 May 13. - Publication Year :
- 2019
-
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.<br />Competing Interests: The authors declare no conflict of interest.
- Subjects :
- Adenosine metabolism
Adenosine pharmacology
Animals
CA3 Region, Hippocampal physiopathology
Disease Models, Animal
Male
Mice
Mice, Transgenic
Optogenetics
Synapses metabolism
Dentate Gyrus physiopathology
Epilepsy physiopathology
Mossy Fibers, Hippocampal drug effects
Mossy Fibers, Hippocampal metabolism
Mossy Fibers, Hippocampal physiopathology
Subjects
Details
- Language :
- English
- ISSN :
- 1091-6490
- Volume :
- 116
- Issue :
- 22
- Database :
- MEDLINE
- Journal :
- Proceedings of the National Academy of Sciences of the United States of America
- Publication Type :
- Academic Journal
- Accession number :
- 31085654
- Full Text :
- https://doi.org/10.1073/pnas.1821227116