Psychology

Dentate gyrus

Status epilepticus

Neuroscience

Epilepsy

Biology

Epileptogenesis

Inhibitory postsynaptic potential

Hippocampus

Hippocampal formation

Interneuron

Nature Neuroscience

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. Shuman et al. report that epileptic mice harbor desynchronized hippocampal interneuron activity and unstable spatial representations, revealing that precise intrahippocampal synchronization is critical for spatial coding.

Breakdown of spatial coding and interneuron synchronization in epileptic mice