Multimodal monitoring of human cortical organoids implanted in mice reveal functional connection with visual cortex.


Journal

Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555

Informations de publication

Date de publication:
26 12 2022
Historique:
received: 04 09 2021
accepted: 09 12 2022
entrez: 26 12 2022
pubmed: 27 12 2022
medline: 29 12 2022
Statut: epublish

Résumé

Human cortical organoids, three-dimensional neuronal cultures, are emerging as powerful tools to study brain development and dysfunction. However, whether organoids can functionally connect to a sensory network in vivo has yet to be demonstrated. Here, we combine transparent microelectrode arrays and two-photon imaging for longitudinal, multimodal monitoring of human cortical organoids transplanted into the retrosplenial cortex of adult mice. Two-photon imaging shows vascularization of the transplanted organoid. Visual stimuli evoke electrophysiological responses in the organoid, matching the responses from the surrounding cortex. Increases in multi-unit activity (MUA) and gamma power and phase locking of stimulus-evoked MUA with slow oscillations indicate functional integration between the organoid and the host brain. Immunostaining confirms the presence of human-mouse synapses. Implantation of transparent microelectrodes with organoids serves as a versatile in vivo platform for comprehensive evaluation of the development, maturation, and functional integration of human neuronal networks within the mouse brain.

Identifiants

pubmed: 36572698
doi: 10.1038/s41467-022-35536-3
pii: 10.1038/s41467-022-35536-3
pmc: PMC9792589
doi:

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, U.S. Gov't, Non-P.H.S. Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

7945

Subventions

Organisme : NINDS NIH HHS
ID : U19 NS123717
Pays : United States
Organisme : NIBIB NIH HHS
ID : R21 EB026180
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH109885
Pays : United States
Organisme : NEI NIH HHS
ID : R21 EY029466
Pays : United States
Organisme : NIGMS NIH HHS
ID : T32 GM007198
Pays : United States
Organisme : NIBIB NIH HHS
ID : DP2 EB030992
Pays : United States

Informations de copyright

© 2022. The Author(s).

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Auteurs

Madison N Wilson (MN)

Department of Electrical and Computer Engineering, University of California San Diego, La Jolla, CA, USA.

Martin Thunemann (M)

Department of Biomedical Engineering, Boston University, Boston, MA, USA.

Xin Liu (X)

Department of Electrical and Computer Engineering, University of California San Diego, La Jolla, CA, USA.

Yichen Lu (Y)

Department of Electrical and Computer Engineering, University of California San Diego, La Jolla, CA, USA.

Francesca Puppo (F)

Department of Pediatrics, University of California San Diego, School of Medicine, La Jolla, CA, USA.

Jason W Adams (JW)

Department of Pediatrics, University of California San Diego, School of Medicine, La Jolla, CA, USA.
Department of Cellular and Molecular Medicine, University of California San Diego, School of Medicine, La Jolla, CA, USA.

Jeong-Hoon Kim (JH)

Department of Electrical and Computer Engineering, University of California San Diego, La Jolla, CA, USA.

Mehrdad Ramezani (M)

Department of Electrical and Computer Engineering, University of California San Diego, La Jolla, CA, USA.

Donald P Pizzo (DP)

Department of Pathology, University of California San Diego, La Jolla, CA, USA.

Srdjan Djurovic (S)

Department of Medical Genetics, Oslo University Hospital, Oslo, Norway.
NORMENT Center, Oslo, Norway.
Department of Clinical Science, University of Bergen, Bergen, Norway.
K. G. Jebsen Center for Neurodevelopmental Disorders, University of Oslo, Oslo, Norway.

Ole A Andreassen (OA)

NORMENT Center, Oslo, Norway.
K. G. Jebsen Center for Neurodevelopmental Disorders, University of Oslo, Oslo, Norway.
Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway.
Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
Oslo University Hospital, University of Oslo, Oslo, Norway.

Abed AlFatah Mansour (AA)

Laboratory of Genetics, The Salk Institute for Biological Studies, La Jolla, CA, USA.
Department of Medical Neurobiology, The Hebrew University of Jerusalem, Ein Kerem-Jerusalem, Israel.

Fred H Gage (FH)

Laboratory of Genetics, The Salk Institute for Biological Studies, La Jolla, CA, USA.

Alysson R Muotri (AR)

Department of Pediatrics, University of California San Diego, School of Medicine, La Jolla, CA, USA.
Department of Cellular and Molecular Medicine, University of California San Diego, School of Medicine, La Jolla, CA, USA.
Center for Academic Research and Training in Anthropogeny, University of California San Diego, La Jolla, CA, USA.
Archealization Center, University of California San Diego, La Jolla, CA, USA.
Kavli Institute for Brain and Mind, University of California San Diego, La Jolla, CA, USA.

Anna Devor (A)

Department of Biomedical Engineering, Boston University, Boston, MA, USA. adevor@bu.edu.
Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Harvard Medical School, Massachusetts General Hospital, Charlestown, MA, USA. adevor@bu.edu.

Duygu Kuzum (D)

Department of Electrical and Computer Engineering, University of California San Diego, La Jolla, CA, USA. dkuzum@eng.ucsd.edu.

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Classifications MeSH