Radaelli Cristina, Schmitz Matthew, Liu Xiao-Ping, Sawchuk Scott, Opitz-Araya Ximena, Hudson Mark, Taskin Naz, Bertagnolli Darren, Goldy Jeff, Ko Andrew L, Grannan Benjamin L, Hauptman Jason S, Patel Anoop P, Cobbs Charles, Smith Kimberly A, Spain William J, Lein Ed S, Bakken Trygve, Dembrow Nikolai C, Ting Jonathan T, Kalmbach Brian E
Allen Institute for Brain Science, Seattle, WA 98109, USA.
Department of Neurobiology and Biophysics, University of Washington, Seattle, WA 98195, USA.
bioRxiv. 2025 Aug 23:2025.08.22.671856. doi: 10.1101/2025.08.22.671856.
The physiological properties of human and rodent neurons differ, yet the extent to which these differences reflect human specializations is often unclear. Compared with their rodent counterparts, human supragranular pyramidal neurons possess enriched HCN-channel-dependent intrinsic membrane properties and a related sensitivity to synaptic inputs containing delta/theta band frequencies. We tested whether other primate species possess enriched HCN-channel dependent membrane properties. We found ubiquitous subunit gene expression in supragranular glutamatergic neurons across New World Monkeys, Old-World Monkeys, and great apes in single nucleus RNA-sequencing datasets. Using Patch-seq recordings from acute and cultured brain slices, we found robust HCN-dependent physiological properties in supragranular pyramidal neurons in a species of New-World monkey () and two species of Old-World Monkey (). In both human and macaque neocortex, HCN-related intrinsic properties increased in magnitude with increasing laminar depth, especially in one transcriptomic cell type. Within this type, HCN dependent properties were more pronounced in macaque than human neurons. These findings indicate that HCN-governed membrane properties and sensitivity to delta/theta band frequencies are roughly conserved in supragranular pyramidal neurons across at least 36 million years of primate evolution.
人类和啮齿动物神经元的生理特性有所不同，但这些差异在多大程度上反映了人类的特殊性往往并不明确。与啮齿动物的对应神经元相比，人类颗粒上层锥体神经元具有丰富的依赖于HCN通道的内在膜特性，以及对包含δ/θ频段频率的突触输入的相关敏感性。我们测试了其他灵长类物种是否具有丰富的依赖于HCN通道的膜特性。我们在单核RNA测序数据集中发现，在新大陆猴、旧大陆猴和大猩猩的颗粒上层谷氨酸能神经元中普遍存在亚基基因表达。通过对急性和培养脑片进行膜片钳-测序记录，我们在一种新大陆猴（ ）和两种旧大陆猴（ ）的颗粒上层锥体神经元中发现了强大的依赖于HCN的生理特性。在人类和猕猴新皮层中，与HCN相关的内在特性随着层深增加而增强，尤其是在一种转录组细胞类型中。在这种类型中，猕猴神经元的HCN依赖性特性比人类神经元更明显。这些发现表明，在至少3600万年的灵长类进化过程中，颗粒上层锥体神经元中由HCN调控的膜特性以及对δ/θ频段频率的敏感性大致保守。
