Modeling Human Brain Circuitry Using Pluripotent Stem Cell Platforms

Neural circuits are the underlying functional units of the human brain that govern complex behavior and higher-order cognitive processes. Disruptions in neural circuit development have been implicated in the pathogenesis of multiple neurodevelopmental disorders such as autism spectrum disorder (ASD)...

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Main Authors: Annalisa M. Hartlaub, Craig A. McElroy, Nathalie L. Maitre, Mark E. Hester
Format: Article
Language:English
Published: Frontiers Media S.A. 2019-03-01
Series:Frontiers in Pediatrics
Subjects:
Online Access:https://www.frontiersin.org/article/10.3389/fped.2019.00057/full
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author Annalisa M. Hartlaub
Craig A. McElroy
Nathalie L. Maitre
Mark E. Hester
author_facet Annalisa M. Hartlaub
Craig A. McElroy
Nathalie L. Maitre
Mark E. Hester
author_sort Annalisa M. Hartlaub
collection DOAJ
description Neural circuits are the underlying functional units of the human brain that govern complex behavior and higher-order cognitive processes. Disruptions in neural circuit development have been implicated in the pathogenesis of multiple neurodevelopmental disorders such as autism spectrum disorder (ASD), attention deficit hyperactivity disorder (ADHD), and schizophrenia. Until recently, major efforts utilizing neurological disease modeling platforms based on human induced pluripotent stem cells (hiPSCs), investigated disease phenotypes primarily at the single cell level. However, recent advances in brain organoid systems, microfluidic devices, and advanced optical and electrical interfaces, now allow more complex hiPSC-based systems to model neuronal connectivity and investigate the specific brain circuitry implicated in neurodevelopmental disorders. Here we review emerging research advances in studying brain circuitry using in vitro and in vivo disease modeling platforms including microfluidic devices, enhanced functional recording interfaces, and brain organoid systems. Research efforts in these areas have already yielded critical insights into pathophysiological mechanisms and will continue to stimulate innovation in this promising area of translational research.
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spelling doaj.art-74e0f93ba205453ea6ca759f0f31cc262022-12-21T23:04:09ZengFrontiers Media S.A.Frontiers in Pediatrics2296-23602019-03-01710.3389/fped.2019.00057441422Modeling Human Brain Circuitry Using Pluripotent Stem Cell PlatformsAnnalisa M. Hartlaub0Craig A. McElroy1Nathalie L. Maitre2Mark E. Hester3Center for Perinatal Research, The Research Institute at Nationwide Children's Hospital, Columbus, OH, United StatesCollege of Pharmacy, The Ohio State University, Columbus, OH, United StatesCenter for Perinatal Research, The Research Institute at Nationwide Children's Hospital, Columbus, OH, United StatesCenter for Perinatal Research, The Research Institute at Nationwide Children's Hospital, Columbus, OH, United StatesNeural circuits are the underlying functional units of the human brain that govern complex behavior and higher-order cognitive processes. Disruptions in neural circuit development have been implicated in the pathogenesis of multiple neurodevelopmental disorders such as autism spectrum disorder (ASD), attention deficit hyperactivity disorder (ADHD), and schizophrenia. Until recently, major efforts utilizing neurological disease modeling platforms based on human induced pluripotent stem cells (hiPSCs), investigated disease phenotypes primarily at the single cell level. However, recent advances in brain organoid systems, microfluidic devices, and advanced optical and electrical interfaces, now allow more complex hiPSC-based systems to model neuronal connectivity and investigate the specific brain circuitry implicated in neurodevelopmental disorders. Here we review emerging research advances in studying brain circuitry using in vitro and in vivo disease modeling platforms including microfluidic devices, enhanced functional recording interfaces, and brain organoid systems. Research efforts in these areas have already yielded critical insights into pathophysiological mechanisms and will continue to stimulate innovation in this promising area of translational research.https://www.frontiersin.org/article/10.3389/fped.2019.00057/fullhuman induced pluripotent stem cell (hiPSC)cerebral organoidbrain organoidneurodevelopmentmicrofluidicneural circuit
spellingShingle Annalisa M. Hartlaub
Craig A. McElroy
Nathalie L. Maitre
Mark E. Hester
Modeling Human Brain Circuitry Using Pluripotent Stem Cell Platforms
Frontiers in Pediatrics
human induced pluripotent stem cell (hiPSC)
cerebral organoid
brain organoid
neurodevelopment
microfluidic
neural circuit
title Modeling Human Brain Circuitry Using Pluripotent Stem Cell Platforms
title_full Modeling Human Brain Circuitry Using Pluripotent Stem Cell Platforms
title_fullStr Modeling Human Brain Circuitry Using Pluripotent Stem Cell Platforms
title_full_unstemmed Modeling Human Brain Circuitry Using Pluripotent Stem Cell Platforms
title_short Modeling Human Brain Circuitry Using Pluripotent Stem Cell Platforms
title_sort modeling human brain circuitry using pluripotent stem cell platforms
topic human induced pluripotent stem cell (hiPSC)
cerebral organoid
brain organoid
neurodevelopment
microfluidic
neural circuit
url https://www.frontiersin.org/article/10.3389/fped.2019.00057/full
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