Breakdown of spatial coding and interneuron synchronization in epileptic mice
Breakdown of spatial coding and interneuron synchronization in epileptic mice
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DOI：
10.1038/s41593-019-0559-0
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发表时间：
2020-01-06
影响因子：
25
通讯作者：
Golshani, Peyman
中科院分区：
文献类型：
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作者：
Shuman, Tristan;Aharoni, Daniel;Golshani, Peyman
颞叶癫痫导致严重的认知障碍，但其电路机制仍不清楚。癫痫发病过程中中间神经元的死亡和重组可能会破坏海马神经元抑制的同步性。为了验证这一点，我们在头部固定的虚拟导航过程中，用硅探针同时记录了匹罗卡品治疗的癫痫小鼠的CA1和齿状回。我们在癫痫小鼠的CA1和齿状回之间发现了去同步化的中间神经元放电。由于海马区中间神经元控制着信息处理，我们使用一种新型的无线微型示波器测试了CA1空间编码是否在这个去同步的电路中发生了改变。我们发现癫痫小鼠的CA1区细胞是不稳定的，并在一周内完全重新映射。这种空间不稳定性出现在癫痫持续状态后6周左右，也就是在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，不同步的输入会影响CA1放置单元的精度和稳定性。总之，这些结果表明，时间上精确的海马区内沟通对于空间处理至关重要。据报道，癫痫小鼠存在海马区中间神经元活动不同步和空间表征不稳定的现象，揭示了精确的海马区内同步对空间编码至关重要。
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.