Format

Send to

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

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

Author information

1
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.
2
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.
3
Department of Neurosciences and Leuven Brain Institute, KU Leuven, 3000 Leuven, Belgium; Neuro-Electronics Research Flanders, Kapeldreef 75, 3001 Leuven, Belgium; imec, 3001 Leuven, Belgium.
4
Institut de Recherches en Biologie Humaine et Moléculaire (IRIBHM) and ULB Neuroscience Institute (UNI), Université Libre de Bruxelles (ULB), 1070 Brussels, Belgium.
5
VIB-KU Leuven Center for Brain & Disease Research, 3000 Leuven, Belgium.
6
VIB-KU Leuven Center for Brain & Disease Research, 3000 Leuven, Belgium; Department of Neurosciences and Leuven Brain Institute, KU Leuven, 3000 Leuven, Belgium.
7
Institut de Recherches en Biologie Humaine et Moléculaire (IRIBHM) and ULB Neuroscience Institute (UNI), Université Libre de Bruxelles (ULB), 1070 Brussels, Belgium; Laboratoire de Physiologie et Pharmacologie and ULB Neuroscience Institute (UNI), Université Libre de Bruxelles (ULB), 1070 Brussels, Belgium.
8
Max von Pettenkofer-Institute and Gene Center, Ludwig-Maximilians-Universität Munchen, 81377 Munich, Germany.
9
Neuro-Electronics Research Flanders, Kapeldreef 75, 3001 Leuven, Belgium; imec, 3001 Leuven, Belgium; Department of Biology and Leuven Brain Institute, KU Leuven, 3000 Leuven, Belgium; VIB, 3000 Leuven, Belgium. Electronic address: vincent.bonin@nerf.be.
10
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, 3000 Leuven, Belgium; Welbio, Université Libre de Bruxelles (ULB), 1070 Brussels, Belgium. Electronic address: pierre.vanderhaeghen@kuleuven.vib.be.

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.

KEYWORDS:

brain development; cortical neuron; dendritic spine; gcamp6; human brain evolution; multiphoton imaging; pluripotent stem cell; synapse formation; transplantation; visual cortex

PMID:
31761708
DOI:
10.1016/j.neuron.2019.10.002
Free full text

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center