Large-scale neurophysiology and single-cell profiling in human neuroscience

• 成果类型: Review
• 署名作者: Lee, Anthony T.; Chang, Edward F.; Paredes, Mercedes F.; Nowakowski, Tomasz J.
• 署名单位: University of California System; University of California San Francisco; University of California System; University of California San Francisco; University of California System; University of California San Francisco; University of California System; University of California San Francisco; University of California System; University of California San Francisco; University of California System; University of California San Francisco
• 刊物名称: Nature
• ISSN/ISSBN: 0028-4941
• DOI: 10.1038/s41586-024-07405-0
• 发表日期: 2024-06-20
• 页码: 587-595
• 关键词: spinal muscular-atrophy; de-novo mutations; prefrontal cortex; neural ensembles; gene-expression; open-label; brain; schizophrenia; spectrum; therapy

摘要

Advances in large-scale single-unit human neurophysiology, single-cell RNA sequencing, spatial transcriptomics and long-term ex vivo tissue culture of surgically resected human brain tissue have provided an unprecedented opportunity to study human neuroscience. In this Perspective, we describe the development of these paradigms, including Neuropixels and recent brain-cell atlas efforts, and discuss how their convergence will further investigations into the cellular underpinnings of network-level activity in the human brain. Specifically, we introduce a workflow in which functionally mapped samples of human brain tissue resected during awake brain surgery can be cultured ex vivo for multi-modal cellular and functional profiling. We then explore how advances in human neuroscience will affect clinical practice, and conclude by discussing societal and ethical implications to consider. Potential findings from the field of human neuroscience will be vast, ranging from insights into human neurodiversity and evolution to providing cell-type-specific access to study and manipulate diseased circuits in pathology. This Perspective aims to provide a unifying framework for the field of human neuroscience as we welcome an exciting era for understanding the functional cytoarchitecture of the human brain. This Perspective considers the implications of advances in human physiology, single-cell and spatial transcriptomics and long-term culture of resected human brain tissue for the study of network-level activity in human neuroscience.