Reduced synaptic activity in neuronal networks derived from embryonic stem cells of murine Rett syndrome model
Neurodevelopmental diseases such as the Rett syndrome have received renewed attention, since the mechanisms involved may underlie a broad range of neuropsychiatric disorders such as schizophrenia and autism. In vertebrates early stages in the functional development of neurons and neuronal networks a...
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doaj-aa38c7f5a96f4cc8984e93c59bc27c6f2020-11-25T00:10:46ZengFrontiers Media S.A.Frontiers in Cellular Neuroscience1662-51022014-03-01810.3389/fncel.2014.0007978615Reduced synaptic activity in neuronal networks derived from embryonic stem cells of murine Rett syndrome modelLydia eBarth0Rosmarie eSütterlin1Markus eNenniger2Kaspar Emanuel Vogt3University of BaselUniversity of BaselUniversity of BaselUniversity of BaselNeurodevelopmental diseases such as the Rett syndrome have received renewed attention, since the mechanisms involved may underlie a broad range of neuropsychiatric disorders such as schizophrenia and autism. In vertebrates early stages in the functional development of neurons and neuronal networks are difficult to study. Embryonic stem cell-derived neurons provide an easily accessible tool to investigate neuronal differentiation and early network formation. We used in vitro cultures of neurons derived from murine embryonic stem cells missing the methyl-CpG-binding protein 2 (MECP2) gene (MeCP2-/y) and from wild type cells of the corresponding background. Cultures were assessed using whole-cell patch-clamp electrophysiology and immunofluorescence. We studied the functional maturation of developing neurons and the activity of the synaptic connections they formed. Neurons exhibited minor differences in the developmental patterns for their intrinsic parameters, such as resting membrane potential and excitability; with the MeCP2-/y cells showing a slightly accelerated development, with shorter action potential half-widths at early stages. There was no difference in the early phase of synapse development, but as the cultures matured, significant deficits became apparent, particularly for inhibitory synaptic activity. MeCP2-/y embryonic stem cell-derived neuronal cultures show clear developmental deficits that match phenotypes observed in slice preparations and thus provide a compelling tool to further investigate the mechanisms behind Rett syndrome pathophysiology.http://journal.frontiersin.org/Journal/10.3389/fncel.2014.00079/fullElectrophysiologyRett Syndromeexcitabilityneurodevelopmentsynaptic activitystem cell-derived neurons |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Lydia eBarth Rosmarie eSütterlin Markus eNenniger Kaspar Emanuel Vogt |
spellingShingle |
Lydia eBarth Rosmarie eSütterlin Markus eNenniger Kaspar Emanuel Vogt Reduced synaptic activity in neuronal networks derived from embryonic stem cells of murine Rett syndrome model Frontiers in Cellular Neuroscience Electrophysiology Rett Syndrome excitability neurodevelopment synaptic activity stem cell-derived neurons |
author_facet |
Lydia eBarth Rosmarie eSütterlin Markus eNenniger Kaspar Emanuel Vogt |
author_sort |
Lydia eBarth |
title |
Reduced synaptic activity in neuronal networks derived from embryonic stem cells of murine Rett syndrome model |
title_short |
Reduced synaptic activity in neuronal networks derived from embryonic stem cells of murine Rett syndrome model |
title_full |
Reduced synaptic activity in neuronal networks derived from embryonic stem cells of murine Rett syndrome model |
title_fullStr |
Reduced synaptic activity in neuronal networks derived from embryonic stem cells of murine Rett syndrome model |
title_full_unstemmed |
Reduced synaptic activity in neuronal networks derived from embryonic stem cells of murine Rett syndrome model |
title_sort |
reduced synaptic activity in neuronal networks derived from embryonic stem cells of murine rett syndrome model |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Cellular Neuroscience |
issn |
1662-5102 |
publishDate |
2014-03-01 |
description |
Neurodevelopmental diseases such as the Rett syndrome have received renewed attention, since the mechanisms involved may underlie a broad range of neuropsychiatric disorders such as schizophrenia and autism. In vertebrates early stages in the functional development of neurons and neuronal networks are difficult to study. Embryonic stem cell-derived neurons provide an easily accessible tool to investigate neuronal differentiation and early network formation. We used in vitro cultures of neurons derived from murine embryonic stem cells missing the methyl-CpG-binding protein 2 (MECP2) gene (MeCP2-/y) and from wild type cells of the corresponding background. Cultures were assessed using whole-cell patch-clamp electrophysiology and immunofluorescence. We studied the functional maturation of developing neurons and the activity of the synaptic connections they formed. Neurons exhibited minor differences in the developmental patterns for their intrinsic parameters, such as resting membrane potential and excitability; with the MeCP2-/y cells showing a slightly accelerated development, with shorter action potential half-widths at early stages. There was no difference in the early phase of synapse development, but as the cultures matured, significant deficits became apparent, particularly for inhibitory synaptic activity. MeCP2-/y embryonic stem cell-derived neuronal cultures show clear developmental deficits that match phenotypes observed in slice preparations and thus provide a compelling tool to further investigate the mechanisms behind Rett syndrome pathophysiology. |
topic |
Electrophysiology Rett Syndrome excitability neurodevelopment synaptic activity stem cell-derived neurons |
url |
http://journal.frontiersin.org/Journal/10.3389/fncel.2014.00079/full |
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