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异种移植的人皮质神经元揭示了种间特异性发育和功能整合到小鼠视觉回路中。

Xenotransplanted Human Cortical Neurons Reveal Species-Specific Development and Functional Integration into Mouse Visual Circuits.

机构信息

VIB-KU Leuven Center for Brain & Disease Research, 3000 Leuven, Belgium; Department of Neurosciences and Leuven Brain Institute, KU Leuven, 3000 Leuven, Belgium; Institut de Recherches en Biologie Humaine et Moléculaire (IRIBHM) and ULB Neuroscience Institute (UNI), Université Libre de Bruxelles (ULB), 1070 Brussels, Belgium.

VIB-KU Leuven Center for Brain & Disease Research, 3000 Leuven, Belgium; Department of Neurosciences and Leuven Brain Institute, KU Leuven, 3000 Leuven, Belgium; Neuro-Electronics Research Flanders, Kapeldreef 75, 3001 Leuven, Belgium.

出版信息

Neuron. 2019 Dec 4;104(5):972-986.e6. doi: 10.1016/j.neuron.2019.10.002. Epub 2019 Nov 21.

DOI:
10.1016/j.neuron.2019.10.002
PMID:31761708
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6899440/
Abstract

How neural circuits develop in the human brain has remained almost impossible to study at the neuronal level. Here, we investigate human cortical neuron development, plasticity, and function using a mouse/human chimera model in which xenotransplanted human cortical pyramidal neurons integrate as single cells into the mouse cortex. Combined neuronal tracing, electrophysiology, and in vivo structural and functional imaging of the transplanted cells reveal a coordinated developmental roadmap recapitulating key milestones of human cortical neuron development. The human neurons display a prolonged developmental timeline, indicating the neuron-intrinsic retention of juvenile properties as an important component of human brain neoteny. Following maturation, human neurons in the visual cortex display tuned, decorrelated responses to visual stimuli, like mouse neurons, demonstrating their capacity for physiological synaptic integration in host cortical circuits. These findings provide new insights into human neuronal development and open novel avenues for the study of human neuronal function and disease. VIDEO ABSTRACT.

摘要

人类大脑中的神经回路如何发育，在神经元水平上几乎难以研究。在这里，我们使用一种鼠/人嵌合体模型来研究人类皮层神经元的发育、可塑性和功能，在该模型中，异种移植的人类皮层锥体神经元作为单个细胞整合到小鼠皮层中。对移植细胞的联合神经元示踪、电生理学以及在体结构和功能成像揭示了一个协调的发育路线图，该路线图重现了人类皮层神经元发育的关键里程碑。人类神经元表现出延长的发育时间表，这表明神经元内在保留了幼年特性，这是人类大脑新皮质形成的一个重要组成部分。成熟后，视觉皮层中的人类神经元对视觉刺激表现出调谐、去相关的反应，就像小鼠神经元一样，证明了它们在宿主皮层回路中进行生理突触整合的能力。这些发现为人类神经元发育提供了新的见解，并为研究人类神经元功能和疾病开辟了新的途径。视频摘要。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c932/6899440/58564ced2088/gr7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c932/6899440/5b4d9d5a3f5f/fx1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c932/6899440/f9872e19d3b3/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c932/6899440/243e8868f9b2/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c932/6899440/05a9ec192f72/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c932/6899440/91de206faedf/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c932/6899440/b1b2b8e8252e/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c932/6899440/f5348d534e2d/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c932/6899440/58564ced2088/gr7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c932/6899440/5b4d9d5a3f5f/fx1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c932/6899440/f9872e19d3b3/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c932/6899440/243e8868f9b2/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c932/6899440/05a9ec192f72/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c932/6899440/91de206faedf/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c932/6899440/b1b2b8e8252e/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c932/6899440/f5348d534e2d/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c932/6899440/58564ced2088/gr7.jpg

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