Linaro, Daniele;
Vermaercke, Ben;
Iwata, Ryohei;
Ramaswamy, Arjun;
Libé-Philippot, Baptiste;
Boubakar, Leila;
Davis, Brittany A;
... Vanderhaeghen, Pierre; + view all
(2019)
Xenotransplanted Human Cortical Neurons Reveal Species-Specific Development and Functional Integration into Mouse Visual Circuits.
Neuron
, 104
(5)
972-986.e6.
10.1016/j.neuron.2019.10.002.
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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.
| Type: | Article |
|---|---|
| Title: | Xenotransplanted Human Cortical Neurons Reveal Species-Specific Development and Functional Integration into Mouse Visual Circuits |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1016/j.neuron.2019.10.002 |
| Language: | English |
| Additional information: | Copyright © 2019 The Author(s). Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
| Keywords: | brain developmentcortical neurontransplantationpluripotent stem cellhuman brain evolutionvisual cortexsynapse formationmultiphoton imaginggcamp6dendritic spine |
| UCL classification: | UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10150759 |
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