RRC ID 63262
Author Hoang Trung H, Yoshihara T, Nakao A, Hayashida K, Hirata Y, Shirasuna K, Kuwamura M, Nakagawa Y, Kaneko T, Mori Y, Asano M, Kuramoto T.
Title Deficiency of the RIβ subunit of protein kinase A causes body tremor and impaired fear conditioning memory in rats.
Journal Sci Rep
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.
Volume 11(1)
Pages 2039
Published 2021-1-21
DOI 10.1038/s41598-021-81515-x
PII 10.1038/s41598-021-81515-x
PMID 33479380
PMC PMC7820254
MeSH Animals Behavior, Animal / physiology CRISPR-Cas Systems / genetics Cyclic AMP / metabolism Cyclic AMP-Dependent Protein Kinase RIbeta Subunit / genetics* Cyclic AMP-Dependent Protein Kinases / genetics Disease Models, Animal Fear / physiology Hippocampus / metabolism* Hippocampus / pathology Humans Memory / physiology Memory Disorders / genetics* Memory Disorders / physiopathology Mice Mutation / genetics Neuronal Plasticity / genetics Neurons / metabolism Neurons / pathology Rats Tremor / genetics* Tremor / physiopathology
IF 3.998
Rats F344/Stm (StrainID=266)