Deficiency of the RIβ subunit of protein kinase A causes body tremor and impaired fear conditioning memory in rats

Abstract The RIβ subunit of cAMP-dependent protein kinase (PKA), encoded by Prkar1b, is a neuronal isoform of the type I regulatory subunit of PKA. Mice lacking the RIβ subunit exhibit normal long-term potentiation (LTP) in the Schaffer collateral pathway of the hippocampus and normal behavior in th...

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Autores principales: Hieu Hoang Trung, Toru Yoshihara, Akito Nakao, Katsumi Hayashida, Yoshiki Hirata, Koumei Shirasuna, Mitsuru Kuwamura, Yuki Nakagawa, Takehito Kaneko, Yasuo Mori, Masahide Asano, Takashi Kuramoto
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Publicado: Nature Portfolio 2021
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spelling oai:doaj.org-article:5803a07e6fba4723b14dc1cd62900d0b2021-12-02T10:49:29ZDeficiency of the RIβ subunit of protein kinase A causes body tremor and impaired fear conditioning memory in rats10.1038/s41598-021-81515-x2045-2322https://doaj.org/article/5803a07e6fba4723b14dc1cd62900d0b2021-01-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-81515-xhttps://doaj.org/toc/2045-2322Abstract The RIβ subunit of cAMP-dependent protein kinase (PKA), encoded by Prkar1b, is a neuronal isoform of the type I regulatory subunit of PKA. Mice lacking the RIβ subunit exhibit normal long-term potentiation (LTP) in the Schaffer collateral pathway of the hippocampus and normal behavior in the open-field and fear conditioning tests. Here, we combined genetic, electrophysiological, and behavioral approaches to demonstrate that the RIβ subunit was involved in body tremor, LTP in the Schaffer collateral pathway, and fear conditioning memory in rats. Genetic analysis of WTC-furue, a mutant strain with spontaneous tremors, revealed a deletion in the Prkar1b gene of the WTC-furue genome. Prkar1b-deficient rats created by the CRISPR/Cas9 system exhibited body tremor. Hippocampal slices from mutant rats showed deficient LTP in the Schaffer collateral–CA1 synapse. Mutant rats also exhibited decreased freezing time following contextual and cued fear conditioning, as well as increased exploratory behavior in the open field. These findings indicate the roles of the RIβ subunit in tremor pathogenesis and contextual and cued fear memory, and suggest that the hippocampal and amygdala roles of this subunit differ between mice and rats and that rats are therefore beneficial for exploring RIβ function.Hieu Hoang TrungToru YoshiharaAkito NakaoKatsumi HayashidaYoshiki HirataKoumei ShirasunaMitsuru KuwamuraYuki NakagawaTakehito KanekoYasuo MoriMasahide AsanoTakashi KuramotoNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-9 (2021)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Hieu Hoang Trung
Toru Yoshihara
Akito Nakao
Katsumi Hayashida
Yoshiki Hirata
Koumei Shirasuna
Mitsuru Kuwamura
Yuki Nakagawa
Takehito Kaneko
Yasuo Mori
Masahide Asano
Takashi Kuramoto
Deficiency of the RIβ subunit of protein kinase A causes body tremor and impaired fear conditioning memory in rats
description Abstract The RIβ subunit of cAMP-dependent protein kinase (PKA), encoded by Prkar1b, is a neuronal isoform of the type I regulatory subunit of PKA. Mice lacking the RIβ subunit exhibit normal long-term potentiation (LTP) in the Schaffer collateral pathway of the hippocampus and normal behavior in the open-field and fear conditioning tests. Here, we combined genetic, electrophysiological, and behavioral approaches to demonstrate that the RIβ subunit was involved in body tremor, LTP in the Schaffer collateral pathway, and fear conditioning memory in rats. Genetic analysis of WTC-furue, a mutant strain with spontaneous tremors, revealed a deletion in the Prkar1b gene of the WTC-furue genome. Prkar1b-deficient rats created by the CRISPR/Cas9 system exhibited body tremor. Hippocampal slices from mutant rats showed deficient LTP in the Schaffer collateral–CA1 synapse. Mutant rats also exhibited decreased freezing time following contextual and cued fear conditioning, as well as increased exploratory behavior in the open field. These findings indicate the roles of the RIβ subunit in tremor pathogenesis and contextual and cued fear memory, and suggest that the hippocampal and amygdala roles of this subunit differ between mice and rats and that rats are therefore beneficial for exploring RIβ function.
format article
author Hieu Hoang Trung
Toru Yoshihara
Akito Nakao
Katsumi Hayashida
Yoshiki Hirata
Koumei Shirasuna
Mitsuru Kuwamura
Yuki Nakagawa
Takehito Kaneko
Yasuo Mori
Masahide Asano
Takashi Kuramoto
author_facet Hieu Hoang Trung
Toru Yoshihara
Akito Nakao
Katsumi Hayashida
Yoshiki Hirata
Koumei Shirasuna
Mitsuru Kuwamura
Yuki Nakagawa
Takehito Kaneko
Yasuo Mori
Masahide Asano
Takashi Kuramoto
author_sort Hieu Hoang Trung
title Deficiency of the RIβ subunit of protein kinase A causes body tremor and impaired fear conditioning memory in rats
title_short Deficiency of the RIβ subunit of protein kinase A causes body tremor and impaired fear conditioning memory in rats
title_full Deficiency of the RIβ subunit of protein kinase A causes body tremor and impaired fear conditioning memory in rats
title_fullStr Deficiency of the RIβ subunit of protein kinase A causes body tremor and impaired fear conditioning memory in rats
title_full_unstemmed Deficiency of the RIβ subunit of protein kinase A causes body tremor and impaired fear conditioning memory in rats
title_sort deficiency of the riβ subunit of protein kinase a causes body tremor and impaired fear conditioning memory in rats
publisher Nature Portfolio
publishDate 2021
url https://doaj.org/article/5803a07e6fba4723b14dc1cd62900d0b
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