Inositol polyphosphate multikinase mediates extinction of fear memory

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

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)2707-2712
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume116
Issue number7
DOIs
StatePublished - Feb 12 2019

Keywords

  • Fear extinction
  • Inositol polyphosphate multikinase
  • Long-term potentiation
  • Memory

ASJC Scopus subject areas

  • General

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