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Publication : Breakdown of spatial coding and interneuron synchronization in epileptic mice.

First Author  Shuman T Year  2020
Journal  Nat Neurosci Volume  23
Issue  2 Pages  229-238
PubMed ID  31907437 Mgi Jnum  J:291796
Mgi Id  MGI:6405533 Doi  10.1038/s41593-019-0559-0
Citation  Shuman T, et al. (2020) Breakdown of spatial coding and interneuron synchronization in epileptic mice. Nat Neurosci 23(2):229-238
abstractText  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.
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