Inositol polyphosphate multikinase mediates extinction of fear memory

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Title
Inositol polyphosphate multikinase mediates extinction of fear memory
Author(s)
Jina Park; Francesco Longo; Seung Ju Park; Seulgi Lee; Mihyun Bae; Richa Tyagi; Jin-Hee Han; Seyun Kim; Emanuela Santini; Eric Klann; Solomon H. Snyder
Publication Date
2019-02
Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, v.116, no.7, pp.2707 - 2712
Publisher
NATL ACAD SCIENCES
Abstract
Inositol polyphosphate multikinase (IPMK), the key enzyme for the biosynthesis of higher inositol polyphosphates and phosphatidylinositol 3,4,5-trisphosphate, also acts as a versatile signaling player in regulating tissue growth and metabolism. To elucidate neurobehavioral functions of IPMK, we generated mice in which IPMK was deleted from the excitatory neurons of the postnatal forebrain. These mice showed no deficits in either novel object recognition or spatial memory. IPMK conditional knockout mice formed cued fear memory normally but displayed enhanced fear extinction. Signaling analyses revealed dysregulated expression of neural genes accompanied by selective activation of the mechanistic target of rapamycin (mTOR) regulatory enzyme p85 S6 kinase 1 (S6K1) in the amygdala following fear extinction. The IPMK mutants also manifested facilitated hippocampal long-term potentiation. These findings establish a signaling action of IPMK that mediates fear extinction. © 2019 National Academy of Sciences. All Rights Reserved
URI
https://pr.ibs.re.kr/handle/8788114/5720
ISSN
0027-8424
Appears in Collections:
Center for Synaptic Brain Dysfunctions(시냅스 뇌질환 연구단) > Journal Papers (저널논문)
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