Development of a platform to investigate long-term potentiation in human iPSC-derived neuronal networks.
Stem Cell Reports
; 17(9): 2141-2155, 2022 09 13.
Article
em En
| MEDLINE
| ID: mdl-35985330
ABSTRACT
Impairment of long-term potentiation (LTP) is a common feature of many pre-clinical models of neurological disorders; however, studies in humans are limited by the inaccessibility of the brain. Human induced pluripotent stem cells (hiPSCs) provide a unique opportunity to study LTP in disease-specific genetic backgrounds. Here we describe a multi-electrode array (MEA)-based assay to investigate chemically induced LTP (cLTP) across entire networks of hiPSC-derived midbrain dopaminergic (DA) and cortical neuronal populations that lasts for days, allowing studies of the late phases of LTP and enabling detection of associated molecular changes. We show that cLTP on midbrain DA neuronal networks is largely independent of the N-methyl-D-aspartate receptor (NMDAR) and partially dependent on brain-derived neurotrophic factor (BDNF). Finally, we describe activity-regulated gene expression induced by cLTP. This cLTP-MEA assay platform will enable phenotype discovery and higher-throughput analyses of synaptic plasticity on hiPSC-derived neurons.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Potenciação de Longa Duração
/
Células-Tronco Pluripotentes Induzidas
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Ano de publicação:
2022
Tipo de documento:
Article