Human stem cell-derived GABAergic neurons functionally integrate into human neuronal networks

Abstract Gamma-aminobutyric acid (GABA)-releasing interneurons modulate neuronal network activity in the brain by inhibiting other neurons. The alteration or absence of these cells disrupts the balance between excitatory and inhibitory processes, leading to neurological disorders such as epilepsy. I...

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Autores principales:	Ana Gonzalez-Ramos, Eliška Waloschková, Apostolos Mikroulis, Zaal Kokaia, Johan Bengzon, Marco Ledri, My Andersson, Merab Kokaia
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/a2e6959621cd4950a88ad99f5f68143b
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spelling	oai:doaj.org-article:a2e6959621cd4950a88ad99f5f68143b2021-11-14T12:21:13ZHuman stem cell-derived GABAergic neurons functionally integrate into human neuronal networks10.1038/s41598-021-01270-x2045-2322https://doaj.org/article/a2e6959621cd4950a88ad99f5f68143b2021-11-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-01270-xhttps://doaj.org/toc/2045-2322Abstract Gamma-aminobutyric acid (GABA)-releasing interneurons modulate neuronal network activity in the brain by inhibiting other neurons. The alteration or absence of these cells disrupts the balance between excitatory and inhibitory processes, leading to neurological disorders such as epilepsy. In this regard, cell-based therapy may be an alternative therapeutic approach. We generated light-sensitive human embryonic stem cell (hESC)-derived GABAergic interneurons (hdIN) and tested their functionality. After 35 days in vitro (DIV), hdINs showed electrophysiological properties and spontaneous synaptic currents comparable to mature neurons. In co-culture with human cortical neurons and after transplantation (AT) into human brain tissue resected from patients with drug-resistant epilepsy, light-activated channelrhodopsin-2 (ChR2) expressing hdINs induced postsynaptic currents in human neurons, strongly suggesting functional efferent synapse formation. These results provide a proof-of-concept that hESC-derived neurons can integrate and modulate the activity of a human host neuronal network. Therefore, this study supports the possibility of precise temporal control of network excitability by transplantation of light-sensitive interneurons.Ana Gonzalez-RamosEliška WaloschkováApostolos MikroulisZaal KokaiaJohan BengzonMarco LedriMy AnderssonMerab KokaiaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-16 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Ana Gonzalez-Ramos Eliška Waloschková Apostolos Mikroulis Zaal Kokaia Johan Bengzon Marco Ledri My Andersson Merab Kokaia Human stem cell-derived GABAergic neurons functionally integrate into human neuronal networks
description	Abstract Gamma-aminobutyric acid (GABA)-releasing interneurons modulate neuronal network activity in the brain by inhibiting other neurons. The alteration or absence of these cells disrupts the balance between excitatory and inhibitory processes, leading to neurological disorders such as epilepsy. In this regard, cell-based therapy may be an alternative therapeutic approach. We generated light-sensitive human embryonic stem cell (hESC)-derived GABAergic interneurons (hdIN) and tested their functionality. After 35 days in vitro (DIV), hdINs showed electrophysiological properties and spontaneous synaptic currents comparable to mature neurons. In co-culture with human cortical neurons and after transplantation (AT) into human brain tissue resected from patients with drug-resistant epilepsy, light-activated channelrhodopsin-2 (ChR2) expressing hdINs induced postsynaptic currents in human neurons, strongly suggesting functional efferent synapse formation. These results provide a proof-of-concept that hESC-derived neurons can integrate and modulate the activity of a human host neuronal network. Therefore, this study supports the possibility of precise temporal control of network excitability by transplantation of light-sensitive interneurons.
format	article
author	Ana Gonzalez-Ramos Eliška Waloschková Apostolos Mikroulis Zaal Kokaia Johan Bengzon Marco Ledri My Andersson Merab Kokaia
author_facet	Ana Gonzalez-Ramos Eliška Waloschková Apostolos Mikroulis Zaal Kokaia Johan Bengzon Marco Ledri My Andersson Merab Kokaia
author_sort	Ana Gonzalez-Ramos
title	Human stem cell-derived GABAergic neurons functionally integrate into human neuronal networks
title_short	Human stem cell-derived GABAergic neurons functionally integrate into human neuronal networks
title_full	Human stem cell-derived GABAergic neurons functionally integrate into human neuronal networks
title_fullStr	Human stem cell-derived GABAergic neurons functionally integrate into human neuronal networks
title_full_unstemmed	Human stem cell-derived GABAergic neurons functionally integrate into human neuronal networks
title_sort	human stem cell-derived gabaergic neurons functionally integrate into human neuronal networks
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/a2e6959621cd4950a88ad99f5f68143b
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Human stem cell-derived GABAergic neurons functionally integrate into human neuronal networks

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