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dc.contributor.authorLiang, Bo
dc.contributor.authorThapa, Rashmi
dc.contributor.authorZhang, Gracie
dc.contributor.authorMoffitt, Casey
dc.contributor.authorZhang, Yan
dc.contributor.authorZhang, Lifeng
dc.contributor.authorJohnston, Amanda
dc.contributor.authorRuby, Hyrum P
dc.contributor.authorBarbera, Giovanni
dc.contributor.authorWong, Philip C
dc.contributor.authorZhang, Zhaojie
dc.contributor.authorChen, Rong
dc.contributor.authorLin, Da-Ting
dc.contributor.authorLi, Yun
dc.date.accessioned2022-06-21T14:30:03Z
dc.date.available2022-06-21T14:30:03Z
dc.date.issued2022-06-04
dc.identifier.urihttp://hdl.handle.net/10713/19216
dc.description.abstractMislocalization of TAR DNA binding protein 43 kDa (TARDBP, or TDP-43) is a principal pathological hallmark identified in cases of neurodegenerative disorders such as amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). As an RNA binding protein, TDP-43 serves in the nuclear compartment to repress non-conserved cryptic exons to ensure the normal transcriptome. Multiple lines of evidence from animal models and human studies support the view that loss of TDP-43 leads to neuron loss, independent of its cytosolic aggregation. However, the underlying pathogenic pathways driven by the loss-of-function mechanism are still poorly defined. We employed a genetic approach to determine the impact of TDP-43 loss in pyramidal neurons of the prefrontal cortex (PFC). Using a custom-built miniscope imaging system, we performed repetitive in vivo calcium imaging from freely behaving mice for up to 7 months. By comparing calcium activity in PFC pyramidal neurons between TDP-43 depleted and TDP-43 intact mice, we demonstrated remarkably increased numbers of pyramidal neurons exhibiting hyperactive calcium activity after short-term TDP-43 depletion, followed by rapid activity declines prior to neuron loss. Our results suggest aberrant neural activity driven by loss of TDP-43 as the pathogenic pathway at early stage in ALS and FTD.en_US
dc.description.urihttps://doi.org/10.1016/j.pneurobio.2022.102297en_US
dc.language.isoenen_US
dc.publisherElsevieren_US
dc.relation.ispartofProgress in Neurobiologyen_US
dc.rightsCopyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.en_US
dc.subjectAberrant neural activityen_US
dc.subjectHyperactivityen_US
dc.subjectHypoactivityen_US
dc.subjectIn vivo calcium imagingen_US
dc.subjectNeurodegenerative disordersen_US
dc.titleAberrant neural activity in prefrontal pyramidal neurons lacking TDP-43 precedes neuron loss.en_US
dc.typeArticleen_US
dc.identifier.doi10.1016/j.pneurobio.2022.102297
dc.identifier.pmid35667630
dc.source.journaltitleProgress in neurobiology
dc.source.volume215
dc.source.beginpage102297
dc.source.endpage
dc.source.countryEngland


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