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dc.contributor.author
Van Lier, Ben
dc.contributor.author
Hierlemann, Andreas
dc.contributor.author
Knoflach, Frédéric
dc.date.accessioned
2018-10-04T15:37:43Z
dc.date.available
2018-10-04T02:57:22Z
dc.date.available
2018-10-04T15:37:43Z
dc.date.issued
2018
dc.identifier.issn
2167-8359
dc.identifier.other
10.7717/peerj.5543
en_US
dc.identifier.uri
http://hdl.handle.net/20.500.11850/293165
dc.identifier.doi
10.3929/ethz-b-000293165
dc.description.abstract
Dysfunction of the N-methyl-d-aspartate receptor (NMDAR) is thought to play a role in the pathophysiology of neurodevelopmental diseases like schizophrenia. To study the effects of NMDAR dysfunction on synaptic transmission and network oscillations, we used hippocampal tissue of NMDAR subunit GluN2A knockout (KO) mice. Field excitatory postsynaptic potentials were recorded in acute hippocampal slices of adult animals. Synaptic transmission was impaired in GluN2A KO slices compared to wild-type (WT) slices. Further, to investigate whether NMDAR dysfunction would alter neurodevelopment in vitro, we used organotypic hippocampal slice cultures of WT and GluN2A KO mice. Immunostaining performed with cultures kept two, seven, 14, 25 days in vitro (DIV) revealed an increasing expression of parvalbumin (PV) over time. As a functional readout, oscillatory activity induced by the cholinergic agonist carbachol was recorded in cultures kept seven, 13, and 26 DIV using microelectrode arrays. Initial analysis focused on the occurrence of delta, theta, beta and gamma oscillations over genotype, DIV and hippocampal area (CA1, CA3, dentate gyrus (DG)). In a follow-up analysis, we studied the peak frequency and the peak power of each of the four oscillation bands per condition. The occurrence of gamma oscillations displayed an increase by DIV similar to the PV immunostaining. Unlike gamma occurrence, delta, theta, and beta occurrence did not change over time in culture. The peak frequency and peak power in the different bands of the oscillations were not different in slices of WT and GluN2A KO mice. However, the level of PV expression was lower in GluN2A KO compared to WT mice. Given the role of PV-containing fast-spiking basket cells in generation of oscillations and the decreased PV expression in subjects with schizophrenia, the study of gamma oscillations in organotypic hippocampal slices represents a potentially valuable tool for the characterization of novel therapeutic drugs.
en_US
dc.format
application/pdf
en_US
dc.language.iso
en
en_US
dc.publisher
PeerJ
en_US
dc.rights.uri
http://creativecommons.org/licenses/by/4.0/
dc.subject
Schizophrenia
en_US
dc.subject
Oscillation
en_US
dc.subject
Organotypic
en_US
dc.subject
Interneuron
en_US
dc.subject
GluN2A
en_US
dc.subject
Gamma
en_US
dc.subject
MEA
en_US
dc.subject
Hippocampus
en_US
dc.subject
NMDAR
en_US
dc.subject
Parvalbumin
en_US
dc.title
Parvalbumin expression and gamma oscillation occurrence increase over time in a neurodevelopmental model of NMDA receptor dysfunction
en_US
dc.type
Journal Article
dc.rights.license
Creative Commons Attribution 4.0 International
dc.date.published
2018-09-19
ethz.journal.title
PeerJ
ethz.journal.volume
6
en_US
ethz.journal.abbreviated
PeerJ
ethz.pages.start
e5543
en_US
ethz.size
22 p.
en_US
ethz.version.deposit
publishedVersion
en_US
ethz.identifier.wos
ethz.publication.place
London
en_US
ethz.publication.status
published
en_US
ethz.leitzahl
ETH Zürich::00002 - ETH Zürich::00012 - Lehre und Forschung::00007 - Departemente::02060 - Dep. Biosysteme / Dep. of Biosystems Science and Eng.::03684 - Hierlemann, Andreas / Hierlemann, Andreas
ethz.leitzahl.certified
ETH Zürich::00002 - ETH Zürich::00012 - Lehre und Forschung::00007 - Departemente::02060 - Dep. Biosysteme / Dep. of Biosystems Science and Eng.::03684 - Hierlemann, Andreas / Hierlemann, Andreas
ethz.date.deposited
2018-10-04T02:58:16Z
ethz.source
WOS
ethz.eth
yes
en_US
ethz.availability
Open access
en_US
ethz.rosetta.installDate
2018-10-04T15:37:58Z
ethz.rosetta.lastUpdated
2019-02-03T08:12:37Z
ethz.rosetta.versionExported
true
ethz.COinS
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