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dc.contributor.authorMeftah, S
dc.contributor.authorCavallini, A
dc.contributor.authorMurray, TK
dc.contributor.authorJankowski, L
dc.contributor.authorBose, S
dc.contributor.authorAshby, MC
dc.contributor.authorBrown, JT
dc.contributor.authorWitton, J
dc.date.accessioned2024-05-10T10:51:43Z
dc.date.issued2024-04-15
dc.date.updated2024-05-09T10:22:34Z
dc.description.abstractSynapse loss is currently the best biological correlate of cognitive decline in Alzheimer’s disease and other tauopathies. Synapses seem to be highly vulnerable to tau-mediated disruption in neurodegenerative tauopathies. However, it is unclear how and when this leads to alterations in function related to the progression of tauopathy and neurodegeneration. We used the well-characterized rTg4510 mouse model of tauopathy at 5–6 months and 7–8 months of age, respectively, to study the functional impact of cortical synapse loss. The earlier age was used as a model of prodromal tauopathy, with the later age corresponding to more advanced tau pathology and presumed progression of neurodegeneration. Analysis of synaptic protein expression in the somatosensory cortex showed significant reductions in synaptic proteins and NMDA and AMPA receptor subunit expression in rTg4510 mice. Surprisingly, in vitro whole-cell patch clamp electrophysiology from putative pyramidal neurons in layer 2/3 of the somatosensory cortex suggested no functional alterations in layer 4 to layer 2/3 synaptic transmission at 5–6 months. From these same neurons, however, there were alterations in dendritic structure, with increased branching proximal to the soma in rTg4510 neurons. Therefore, in vivo whole-cell patch clamp recordings were utilized to investigate synaptic function and integration in putative pyramidal neurons in layer 2/3 of the somatosensory cortex. These recordings revealed a significant increase in the peak response to synaptically driven sensory stimulation-evoked activity and a loss of temporal fidelity of the evoked signal to the input stimulus in rTg4510 neurons. Together, these data suggest that loss of synapses, changes in receptor expression and dendritic restructuring may lead to alterations in synaptic integration at a network level. Understanding these compensatory processes could identify targets to help delay symptomatic onset of dementia.en_GB
dc.description.sponsorshipMedical Research Council (MRC)en_GB
dc.description.sponsorshipAlzheimer’s Research UKen_GB
dc.description.sponsorshipElizabeth Blackwell Institute, University of Bristolen_GB
dc.description.sponsorshipWellcome Trusten_GB
dc.format.extentfcae134-
dc.identifier.citationVol. 6 (3), article fcae134en_GB
dc.identifier.doihttps://doi.org/10.1093/braincomms/fcae134
dc.identifier.grantnumberMR/N0137941/1en_GB
dc.identifier.grantnumberARUK-PG2017B-7en_GB
dc.identifier.grantnumberARUK-RF2015-6en_GB
dc.identifier.grantnumber204813/Z/16/Zen_GB
dc.identifier.urihttp://hdl.handle.net/10871/135932
dc.identifierORCID: 0000-0001-5269-7661 (Brown, Jonathan T)
dc.identifierScopusID: 56169451300 (Brown, Jonathan T)
dc.identifierORCID: 0000-0001-9411-4022 (Witton, Jonathan)
dc.language.isoenen_GB
dc.publisherOxford University Press (OUP) / Guarantors of Brainen_GB
dc.rights© The Author(s) 2024. Published by Oxford University Press on behalf of the Guarantors of Brain. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.en_GB
dc.titleSynaptic alterations associated with disrupted sensory encoding in a mouse model of tauopathyen_GB
dc.typeArticleen_GB
dc.date.available2024-05-10T10:51:43Z
dc.identifier.issn2632-1297
dc.descriptionThis is the final version. Available on open access from Oxford University Press via the DOI in this recorden_GB
dc.descriptionData availability: The data and analysis code used for this study are available from the corresponding author, upon reasonable request.en_GB
dc.identifier.eissn2632-1297
dc.identifier.journalBrain Communicationsen_GB
dc.relation.ispartofBrain Communications
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/en_GB
dcterms.dateAccepted2024-04-11
rioxxterms.versionVoRen_GB
rioxxterms.licenseref.startdate2024-04-15
rioxxterms.typeJournal Article/Reviewen_GB
refterms.dateFCD2024-05-10T10:48:08Z
refterms.versionFCDVoR
refterms.dateFOA2024-05-10T10:51:44Z
refterms.panelAen_GB
refterms.dateFirstOnline2024-04-15


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© The Author(s) 2024. Published by Oxford University Press on behalf of the Guarantors of Brain. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
Except where otherwise noted, this item's licence is described as © The Author(s) 2024. Published by Oxford University Press on behalf of the Guarantors of Brain. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.