Chameh Homeira Moradi, Falby Madeleine, Movahed Mandana, Arbabi Keon, Rich Scott, Zhang Liang, Lefebvre Jérémie, Tripathy Shreejoy J, De Pittà Maurizio, Valiante Taufik A
Division of Clinical and Computational Neuroscience, Krembil Brain Institute, University Health Network (UHN), Toronto, ON, Canada.
Institute of Medical Science, University of Toronto, Toronto, ON, Canada.
Front Synaptic Neurosci. 2023 Oct 4;15:1250834. doi: 10.3389/fnsyn.2023.1250834. eCollection 2023.
Electrophysiological characterization of live human tissue from epilepsy patients has been performed for many decades. Although initially these studies sought to understand the biophysical and synaptic changes associated with human epilepsy, recently, it has become the mainstay for exploring the distinctive biophysical and synaptic features of human cell-types. Both epochs of these human cellular electrophysiological explorations have faced criticism. Early studies revealed that cortical pyramidal neurons obtained from individuals with epilepsy appeared to function "normally" in comparison to neurons from non-epilepsy controls or neurons from other species and thus there was little to gain from the study of human neurons from epilepsy patients. On the other hand, contemporary studies are often questioned for the "normalcy" of the recorded neurons since they are derived from epilepsy patients. In this review, we discuss our current understanding of the distinct biophysical features of human cortical neurons and glia obtained from tissue removed from patients with epilepsy and tumors. We then explore the concept of within cell-type diversity and its loss (i.e., "neural homogenization"). We introduce neural homogenization to help reconcile the epileptogenicity of seemingly "normal" human cortical cells and circuits. We propose that there should be continued efforts to study cortical tissue from epilepsy patients in the quest to understand what makes human cell-types "human".
对癫痫患者的活体人体组织进行电生理特性分析已经开展了数十年。尽管最初这些研究旨在了解与人类癫痫相关的生物物理和突触变化，但最近，它已成为探索人类细胞类型独特生物物理和突触特征的主要手段。这些人体细胞电生理探索的两个阶段都面临批评。早期研究表明，与非癫痫对照个体的神经元或其他物种的神经元相比，从癫痫患者获取的皮质锥体神经元似乎“正常”运作，因此研究癫痫患者的人类神经元收获甚微。另一方面，当代研究常常因其记录的神经元来自癫痫患者而对其“正常性”受到质疑。在这篇综述中，我们讨论了我们目前对从癫痫患者和肿瘤患者切除的组织中获得的人类皮质神经元和神经胶质独特生物物理特征的理解。然后我们探讨了细胞类型内多样性及其丧失（即“神经同质化”）的概念。我们引入神经同质化以帮助调和看似“正常”的人类皮质细胞和回路的致痫性。我们建议应继续努力研究癫痫患者的皮质组织，以寻求理解是什么使人类细胞类型具有“人性”。
