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dc.contributor.authorCharlesworth, Paul
dc.contributor.authorMorton, Andrew
dc.contributor.authorEglen, Stephen J
dc.contributor.authorKomiyama, Noboru H
dc.contributor.authorGrant, Seth G N
dc.date.accessioned2015-08-27T14:10:02Z
dc.date.available2015-08-27T14:10:02Z
dc.date.issued2015
dc.identifier.citationCharlesworth , P , Morton , A , Eglen , S J , Komiyama , N H & Grant , S G N 2015 , ' Canalization of genetic and pharmacological perturbations in developing primary neuronal activity patterns ' , Neuropharmacology , vol. In press . https://doi.org/10.1016/j.neuropharm.2015.07.027en
dc.identifier.issn0028-3908
dc.identifier.otherPURE: 207298168
dc.identifier.otherPURE UUID: c4ded30b-07ef-4441-84dd-11f592c56511
dc.identifier.otherPubMed: 26211975
dc.identifier.otherScopus: 84942365437
dc.identifier.urihttp://hdl.handle.net/10023/7339
dc.descriptionPC, AM, NHK and SGNG were supported by the Wellcome Trust Genes to Cognition programme and European Union programs (Project GENCODYS no. 241995, Project EUROSPIN no. 242498 and Project SYNSYS no. 242167) and SJE was supported by the CARMEN e-science project (www.carmen.org.uk) funded by the EPSRC (EP/E002331/1).en
dc.description.abstractThe function of the nervous system depends on the integrity of synapses and the patterning of electrical activity in brain circuits. The rapid advances in genome sequencing reveal a large number of mutations disrupting synaptic proteins, which potentially result in diseases known as synaptopathies. However, it is also evident that every normal individual carries hundreds of potentially damaging mutations. Although genetic studies in several organisms show that mutations can be masked during development by a process known as canalization, it is unknown if this occurs in the development of the electrical activity in the brain. Using longitudinal recordings of primary cultured neurons on multi-electrode arrays from mice carrying knockout mutations we report evidence of canalization in development of spontaneous activity patterns. Phenotypes in the activity patterns in young cultures from mice lacking the Gria1 subunit of the AMPA receptor were ameliorated as cultures matured. Similarly, the effects of chronic pharmacological NMDA receptor blockade diminished as cultures matured. Moreover, disturbances in activity patterns by simultaneous disruption of Gria1 and NMDA receptors were also canalized by three weeks in culture. Additional mutations and genetic variations also appeared to be canalized to varying degrees. These findings indicate that neuronal network canalization is a form of nervous system plasticity that provides resilience to developmental disruption.
dc.language.isoeng
dc.relation.ispartofNeuropharmacologyen
dc.rights© 2015 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).en
dc.subjectSynapseen
dc.subjectNeuronen
dc.subjectNetworken
dc.subjectMutationen
dc.subjectCanalizationen
dc.subjectRC0321 Neuroscience. Biological psychiatry. Neuropsychiatryen
dc.subjectNDASen
dc.subject.lccRC0321en
dc.titleCanalization of genetic and pharmacological perturbations in developing primary neuronal activity patternsen
dc.typeJournal articleen
dc.description.versionPublisher PDFen
dc.contributor.institutionUniversity of St Andrews.School of Physics and Astronomyen
dc.identifier.doihttps://doi.org/10.1016/j.neuropharm.2015.07.027
dc.description.statusPeer revieweden
dc.identifier.urlhttp://www.sciencedirect.com/science/article/pii/S0028390815300344#appd001en


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