h-Channels Contribute to Divergent Intrinsic Membrane Properties of Supragranular Pyramidal Neurons in Human versus Mouse Cerebral Cortex.
h-Channels Contribute to Divergent Intrinsic Membrane Properties of Supragranular Pyramidal Neurons in Human versus Mouse Cerebral Cortex.
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DOI：
10.1016/j.neuron.2018.10.012
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发表时间：
2018-12-05
期刊：
影响因子：
16.2
通讯作者：
Ting JT
中科院分区：
文献类型：
--
作者：
Kalmbach BE;Buchin A;Long B;Close J;Nandi A;Miller JA;Bakken TE;Hodge RD;Chong P;de Frates R;Dai K;Maltzer Z;Nicovich PR;Keene CD;Silbergeld DL;Gwinn RP;Cobbs C;Ko AL;Ojemann JG;Koch C;Anastassiou CA;Lein ES;Ting JT
基因表达研究表明，不同的离子通道表达有助于啮齿动物与人类神经元生理学的差异。我们测试了与小鼠相比，h通道是否对人类核上锥体神经元的生理特性有更显著的贡献。单细胞/细胞核RNA测序显示人类兴奋性神经元中普遍存在hcn1亚基表达，但小鼠核上层中没有。利用膜片钳记录，我们发现人类颞叶皮层核上锥体神经元的h通道相关膜特性比小鼠颞叶关联区核上锥体神经元强。这些差异的大小取决于皮质深度，在L3深部的锥体神经元中最大。此外，与小鼠相比，药物阻断h通道在人类神经元中产生了更大的膜特性变化。最后，利用生物物理模型，我们提供了h通道促进人类L3锥体神经元从树突到体细胞的θ频率转移的证据。因此，h通道有助于物种之间基本神经元特性的差异。h通道相关基因在人核上皮层的表达比小鼠更为突出。因此，h通道对人类核上锥体神经元生理的影响大于小鼠。这些差异产生了人类核上锥体神经元突触整合的根本差异。
Gene expression studies suggest that differential ion channel expression contributes to differences in rodent versus human neuronal physiology. We tested whether h-channels more prominently contribute to the physiological properties of human compared to mouse supragranular pyramidal neurons. Single cell/nucleus RNA sequencing revealed ubiquitous HCN1-subunit expression in excitatory neurons in human, but not mouse supragranular layers. Using patch-clamp recordings, we found stronger h-channel-related membrane properties in supragranular pyramidal neurons in human temporal cortex, compared to mouse supragranular pyramidal neurons in temporal association area. The magnitude of these differences depended upon cortical depth and was largest in pyramidal neurons in deep L3. Additionally, pharmacologically blocking h-channels produced a larger change in membrane properties in human compared to mouse neurons. Finally, using biophysical modeling, we provided evidence that h-channels promote the transfer of theta frequencies from dendriteto-soma in human L3 pyramidal neurons. Thus, h-channels contribute to between-species differences in a fundamental neuronal property. h-channel-related gene expression is more prominent in human than mouse supragranular cortex. Consequently, h-channels contribute to supragranular pyramidal neuron physiology more in human than mouse neocortex. These differences produce fundamental differences in synaptic integration in human supragranular pyramidal neurons.
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