This work was led by the amazing @susieyufeng.bsky.social but was a huge team effort across the Shuman and Cai Labs!

All of the data is available online and we hope other labs will be able to utilize it to answer other questions about epileptic circuits in MEC and hippocampus.

Altogether, this work suggest that the induction of epilepsy drives a progressive disease state with circuit dysfunction that accumulates and shifts from the hippocampus to medial entorhinal cortex as cognitive impairment progresses.

In particular, the MEC cell type that was most impaired were "Trough-locked" cells in layer 3, which were recently characterized as predictive grid cells (doi.org/10.1126/scie...). Their dysfunction suggests this cell type may be uniquely vulnerable in epilepsy and contribute to memory deficits.

By 8 weeks after pilocarpine, the synchronization within MEC and between MEC and hippocampus became impaired. These deficits aligned with the onset of severe memory impairments, suggesting that changes in MEC may underlie progressive memory impairment in epilepsy.

To investigate the circuits that drive this progressive memory impairment we recorded HPC and MEC simultaneously as epileptic and control mice explored a virtual linear track. We found early changes in theta power, coherence, and interneuron phase locking only in hippocampus, while MEC was intact.

First we found that memory deficits after pilocarpine were progressive, with minor early deficits (within 3 weeks) and more severe deficits 8 weeks after pilocarpine. Yet there were no changes in seizures or cell death across these time points suggesting altered neural activity drives these effects.