美国艾伦脑科学研究所Ed S. Lein等研究人员合作揭示人类和小鼠新皮层第一层中间神经元库的形态电和转录组差异。2023年10月13日出版的《科学》杂志发表了这项成果。

研究人员表示，新皮层1层（L1）是锥体神经元树突和反馈轴突之间的会聚点，其中局部抑制信号可以深刻地影响皮层的处理过程。人类新皮层的演化扩展以具有广泛L1分支的独特锥体神经元为标志，但L1中间神经元是否具有类似的多样性尚不清楚。

利用来自人类神经外科组织的Patch-seq记录，研究人员鉴定了它们的转录组亚类与小鼠L1同源物，以及不同的亚型和小鼠L1不匹配的类型。亚类和亚型比较显示，人类L1的转录组学差异更大，并且在不同于小鼠L1变异的维度上与强形态电变异性相关。伴随着更大的层厚和其他细胞结构的变化，这些发现表明L1在演化中已经分化，反映了调节扩大的人类新皮层回路的需求。

附：英文原文

Title: Morphoelectric and transcriptomic divergence of the layer 1 interneuron repertoire in human versus mouse neocortex

Author: Thomas Chartrand, Rachel Dalley, Jennie Close, Natalia A. Goriounova, Brian R. Lee, Rusty Mann, Jeremy A. Miller, Gabor Molnar, Alice Mukora, Lauren Alfiler, Katherine Baker, Trygve E. Bakken, Jim Berg, Darren Bertagnolli, Thomas Braun, Krissy Brouner, Tamara Casper, Eva Adrienn Csajbok, Nick Dee, Tom Egdorf, Rachel Enstrom, Anna A. Galakhova, Amanda Gary, Emily Gelfand, Jeff Goldy, Kristen Hadley, Tim S. Heistek, DiJon Hill, Nik Jorstad, Lisa Kim, Agnes Katalin Kocsis, Lauren Kruse, Michael Kunst, Gabriela Leon, Brian Long, Matthew Mallory, Medea McGraw, Delissa McMillen, Erica J. Melief, Norbert Mihut, Lindsay Ng, Julie Nyhus, Gáspár Oláh, Attila Ozsvár, Victoria Omstead, Zoltan Peterfi, Alice Pom, Lydia Potekhina, Ramkumar Rajanbabu, Marton Rozsa, Augustin Ruiz, Joanna Sandle, Susan M. Sunkin, Ildiko Szots, Michael Tieu, Martin Toth, Jessica Trinh, Sara Vargas, David Vumbaco, Grace Williams, Julia Wilson, Zizhen Yao, Pal Barzo, Charles Cobbs, Richard G. Ellenbogen, Luke Esposito, Manuel Ferreira, Nathan W. Gouwens, Benjamin Grannan, Ryder P. Gwinn, Jason S. Hauptman, Tim Jarsky, C. Dirk Keene, Andrew L. Ko, Christof Koch, Jeffrey G. Ojemann, Anoop Patel, Jacob Ruzevick, Daniel L. Silbergeld, Kimberly Smith, Staci A. Sorensen, Bosiljka Tasic, Jonathan T. Ting, Jack Waters, Christiaan P.J. de Kock, Huib D. Mansvelder, Gabor Tamas, Hongkui Zeng, Brian Kalmbach, Ed S. Lein

Issue&Volume: 2023-10-13

Abstract: Neocortical layer 1 (L1) is a site of convergence between pyramidal-neuron dendrites and feedback axons where local inhibitory signaling can profoundly shape cortical processing. Evolutionary expansion of human neocortex is marked by distinctive pyramidal neurons with extensive L1 branching, but whether L1 interneurons are similarly diverse is underexplored. Using Patch-seq recordings from human neurosurgical tissue, we identified four transcriptomic subclasses with mouse L1 homologs, along with distinct subtypes and types unmatched in mouse L1. Subclass and subtype comparisons showed stronger transcriptomic differences in human L1 and were correlated with strong morphoelectric variability along dimensions distinct from mouse L1 variability. Accompanied by greater layer thickness and other cytoarchitecture changes, these findings suggest that L1 has diverged in evolution, reflecting the demands of regulating the expanded human neocortical circuit.

DOI: adf0805

Source: https://www.science.org/doi/10.1126/science.adf0805

期刊信息

Science：《科学》，创刊于1880年。隶属于美国科学促进会，最新IF：63.714

官方网址：https://www.sciencemag.org/

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