Circadian regulation of mouse anxiety-like behavior and trial of affective disorder improvement

2016 Fiscal Year Final Research Report

• Project/Area Number: 15K12767
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Basic / Social brain science
• Research Institution: The University of Tokyo
• Principal Investigator: SHIMIZU Kimiko 東京大学, 大学院理学系研究科(理学部), 助教 (50451828)
• Research Collaborator: NAKANO Jun
• Project Period (FY): 2015-04-01 – 2017-03-31
• Keywords: anxiety / circadian / basolateral amygdala / SCOP / PHLPP1β / elevated plus maze / open field test

Outline of Final Research Achievements

We characterized the time-of-day-dependent regulation of mouse anxiety-like behaviors. We show that anxiety-like behaviors are expressed in a circadian manner in mice and demonstrate that the clock machineries in the forebrain are required for the time-of-day-dependent regulation of anxiety-like behaviors. We identifed SCOP/PHLPP1β as an essential intracellular signaling molecule mediating this temporal regulation downstream of the clock. Using viral-mediated, basolateral amygdala (BLA)-specific knockout of Scop, we demonstrate that deletion of Scop in the BLA exerts anxiolytic effects on the elevated plus maze at early subjective night, thereby blunting the circadian variation in the anxiety-like behavior. We conclude that the circadian expression of SCOP in the BLA plays a key role in generating circadian rhythmicity in the anxiety-like behavior. Our results demonstrate SCOP as a regulator of anxiety-like behaviors and reveal its key roles in the anxiogenic functions of the BLA.

Free Research Field

神経分子生物学