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.

颞叶癫痫会导致严重的认知缺陷，但其回路机制仍不清楚。癫痫发生期间的中间神经元死亡和重组可能会破坏海马抑制的同步性。为了测试这一点，我们在头部固定虚拟导航期间用硅探针同时记录毛果芸香碱治疗的癫痫小鼠的 CA1 和齿状回。我们发现癫痫小鼠 CA1 和齿状回之间的中间神经元放电不同步。由于海马中间神经元控制信息处理，我们使用新型无线微型显微镜测试了 CA1 空间编码是否在这种去同步电路中被改变。我们发现癫痫小鼠的 CA1 位置细胞不稳定，并在一周内完全重新定位。这种空间不稳定性出现在癫痫持续状态后约 6 周，即慢性癫痫发作和中间神经元死亡之后很久。最后，CA1 网络建模表明，不同步的输入会损害 CA1 位置单元的精度和稳定性。总之，这些结果表明，时间精确的海马内通信对于空间处理至关重要。