Interdepartmental Program in Neuroscience, University of Utah, Salt Lake City, Utah.
Department of Biomedical Engineering, Boston University, Boston, Massachusetts.
Hippocampus. 2019 Dec;29(12):1178-1189. doi: 10.1002/hipo.23131. Epub 2019 Jul 13.
Numerous synaptic and intrinsic membrane mechanisms have been proposed for generating oscillatory activity in the hippocampus. Few studies, however, have directly measured synaptic conductances and membrane properties during oscillations. The time course and relative contribution of excitatory and inhibitory synaptic conductances, as well as the role of intrinsic membrane properties in amplifying synaptic inputs, remains unclear. To address this issue, we used an isolated whole hippocampal preparation that generates autonomous low-frequency oscillations near the theta range. Using 2-photon microscopy and expression of genetically encoded fluorophores, we obtained on-cell and whole-cell patch recordings of pyramidal cells and fast-firing interneurons in the distal subiculum. Pyramidal cell and interneuron spiking shared similar phase-locking to local field potential oscillations. In pyramidal cells, spiking resulted from a concomitant and balanced increase in excitatory and inhibitory synaptic currents. In contrast, interneuron spiking was driven almost exclusively by excitatory synaptic current. Thus, similar to tightly balanced networks underlying hippocampal gamma oscillations and ripples, balanced synaptic inputs in the whole hippocampal preparation drive highly phase-locked spiking at the peak of slower network oscillations.
已有大量的突触和膜内在机制被提出用于产生海马体中的振荡活动。然而,很少有研究直接测量在振荡过程中的突触电导和膜性质。兴奋性和抑制性突触电导的时间进程和相对贡献,以及内在膜性质在放大突触输入中的作用仍不清楚。为了解决这个问题,我们使用了一个能够在θ频段附近产生自主低频振荡的分离的全海马体准备。通过双光子显微镜和遗传编码荧光蛋白的表达,我们在远端下托区获得了锥体神经元和快速放电中间神经元的细胞膜片钳记录。锥体神经元和中间神经元的放电与局部场电位振荡具有相似的锁相。在锥体神经元中,放电是由兴奋性和抑制性突触电流的同时和平衡增加引起的。相比之下,中间神经元的放电几乎完全由兴奋性突触电流驱动。因此,类似于海马体γ振荡和涟漪的紧密平衡网络,全海马体准备中的平衡突触输入在较慢网络振荡的峰值处驱动高度锁相的放电。