Breakdown of spatial coding and interneuron synchronization in epileptic mice

Temporal lobe epilepsy causes severe cognitive deficits, but the circuit mechanisms remain unknown. Interneuron death and reorganization during epileptogenesis may disrupt the synchrony of hippocampal inhibition. To test this, we simultaneously recorded from the CA1 and dentate gyrus in pilocarpine-...

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Vydáno v:Nature neuroscience Ročník 23; číslo 2; s. 229 - 238
Hlavní autoři: Shuman, Tristan, Aharoni, Daniel, Cai, Denise J, Lee, Christopher R, Chavlis, Spyridon, Page-Harley, Lucia, Vetere, Lauren M, Feng, Yu, Yang, Chen Yi, Mollinedo-Gajate, Irene, Chen, Lingxuan, Pennington, Zachary T, Taxidis, Jiannis, Flores, Sergio E, Cheng, Kevin, Javaherian, Milad, Kaba, Christina C, Rao, Naina, La-Vu, Mimi, Pandi, Ioanna, Shtrahman, Matthew, Bakhurin, Konstantin I, Masmanidis, Sotiris C, Khakh, Baljit S, Poirazi, Panayiota, Silva, Alcino J, Golshani, Peyman
Médium: Journal Article
Jazyk:angličtina
Vydáno: United States Nature Publishing Group 01.02.2020
Témata:
Animals
CA1 Region, Hippocampal - physiopathology
Cell interactions
Circuits
Coding
Cognitive ability
Data processing
Dentate gyrus
Dentate Gyrus - physiopathology
Epilepsy
Epilepsy, Temporal Lobe - physiopathology
Hippocampus
Information processing
Interneurons
Interneurons - physiology
Male
Mice
Mice, Inbred C57BL
Neural Pathways - physiopathology
Pilocarpine
Seizures
Synchronism
Synchronization
Temporal lobe
ISSN:1097-6256, 1546-1726, 1546-1726
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Shrnutí:Temporal lobe epilepsy causes severe cognitive deficits, but the circuit mechanisms remain unknown. Interneuron death and reorganization during epileptogenesis may disrupt the synchrony of hippocampal inhibition. To test this, we simultaneously recorded from the CA1 and dentate gyrus in pilocarpine-treated epileptic mice with silicon probes during head-fixed virtual navigation. We found desynchronized interneuron firing between the CA1 and dentate gyrus in epileptic mice. Since hippocampal interneurons control information processing, we tested whether CA1 spatial coding was altered in this desynchronized circuit, using a novel wire-free miniscope. We found that CA1 place cells in epileptic mice were unstable and completely remapped across a week. This spatial instability emerged around 6 weeks after status epilepticus, well after the onset of chronic seizures and interneuron death. Finally, CA1 network modeling showed that desynchronized inputs can impair the precision and stability of CA1 place cells. Together, these results demonstrate that temporally precise intrahippocampal communication is critical for spatial processing.
Bibliografie:ObjectType-Article-1
SourceType-Scholarly Journals-1
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ISSN:1097-6256
1546-1726
1546-1726
DOI:10.1038/s41593-019-0559-0