Breakdown of spatial coding and interneuron synchronization in epileptic mice

Nat Neurosci. 2020 Feb;23(2):229-238. doi: 10.1038/s41593-019-0559-0. Epub 2020 Jan 6.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • CA1 Region, Hippocampal / physiopathology*
  • Dentate Gyrus / physiopathology*
  • Epilepsy, Temporal Lobe / physiopathology*
  • Interneurons / physiology*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Neural Pathways / physiopathology*