Xenotransplanted Human Cortical Neurons Reveal Species-Specific Development and Functional Integration into Mouse Visual Circuits.
brain development
cortical neuron
dendritic spine
gcamp6
human brain evolution
multiphoton imaging
pluripotent stem cell
synapse formation
transplantation
visual cortex
Journal
Neuron
ISSN: 1097-4199
Titre abrégé: Neuron
Pays: United States
ID NLM: 8809320
Informations de publication
Date de publication:
04 12 2019
04 12 2019
Historique:
received:
02
05
2019
revised:
12
08
2019
accepted:
30
09
2019
pubmed:
26
11
2019
medline:
24
3
2020
entrez:
26
11
2019
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 31761708
pii: S0896-6273(19)30850-5
doi: 10.1016/j.neuron.2019.10.002
pmc: PMC6899440
pii:
doi:
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
972-986.e6Informations de copyright
Copyright © 2019 The Author(s). Published by Elsevier Inc. All rights reserved.
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