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Sökning: onr:"swepub:oai:prod.swepub.kib.ki.se:146414015" > Ablation of p75NTR ...

LIBRIS Formathandbok  (Information om MARC21)
FältnamnIndikatorerMetadata
00003234naa a2200325 4500
001oai:prod.swepub.kib.ki.se:146414015
003SwePub
008240811s2021 | |||||||||||000 ||eng|
024a http://kipublications.ki.se/Default.aspx?queryparsed=id:1464140152 URI
024a https://doi.org/10.1038/s41398-021-01332-82 DOI
040 a (SwePub)ki
041 a engb eng
042 9 SwePub
072 7a ref2 swepub-contenttype
072 7a art2 swepub-publicationtype
100a Andrade-Talavera, Yu Karolinska Institutet4 aut
2451 0a Ablation of p75NTR signaling strengthens gamma-theta rhythm interaction and counteracts Aβ-induced degradation of neuronal dynamics in mouse hippocampus in vitro
264 c 2021-04-09
264 1b Springer Science and Business Media LLC,c 2021
520 a Gamma and theta brain rhythms play important roles in cognition and their interaction can affect gamma oscillation features. Hippocampal theta oscillations depend on cholinergic and GABAergic input from the medial septum-diagonal band of Broca. These projecting neurons undergo degeneration during aging and maintain high levels of neurotrophin receptor p75 (p75NTR). p75NTR mediates both apoptosis and survival and its expression is increased in Alzheimer’s disease (AD) patients. Here, we investigate the importance of p75NTR for the cholinergic input to the hippocampus. Performing extracellular recordings in brain slices from p75NTR knockout mice (p75−/−) in presence of the muscarinic agonist carbachol, we find that gamma oscillation power and rhythmicity are increased compared to wild-type (WT) mice. Furthermore, gamma activity is more phase-locked to the underlying theta rhythm, which renders a stronger coupling of both rhythms. On the cellular level, we find that fast-spiking interneurons (FSNs) fire more synchronized to a preferred gamma phase in p75−/− mice. The excitatory input onto FSN is more rhythmic displaying a higher similarity with the concomitant gamma rhythm. Notably, the ablation of p75NTR counteracts the Aβ-induced degradation of gamma oscillations and its nesting within the underlying theta rhythm. Our results show that the lack of p75NTR signaling could promote stronger cholinergic modulation of the hippocampal gamma rhythm, suggesting an involvement of p75NTR in the downregulation of cognition-relevant hippocampal network dynamics in pathologies. Moreover, functional data provided here suggest p75NTR as a suitable target in the search for efficacious treatments to counteract the loss of cognitive function observed in amyloid-driven pathologies such as AD.
700a Balleza-Tapia, H4 aut
700a Dolz-Gaiton, P4 aut
700a Chen, GFu Karolinska Institutet4 aut
700a Johansson, Ju Karolinska Institutet4 aut
700a Fisahn, Au Karolinska Institutet4 aut
710a Karolinska Institutet4 org
773t Translational psychiatryd : Springer Science and Business Media LLCg 11:1, s. 212-q 11:1<212-x 2158-3188
856u https://www.nature.com/articles/s41398-021-01332-8.pdf
8564 8u http://kipublications.ki.se/Default.aspx?queryparsed=id:146414015
8564 8u https://doi.org/10.1038/s41398-021-01332-8

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