SCOP/PHLPP1β in the basolateral amygdala regulates circadian expression of mouse anxiety-like behavior

Abstract

While disruption of the circadian clock triggers a spectrum of affective abnormalities, how the clock regulates mammalian emotionality remains unclear. Here, 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 dorsal telencephalon (dTel) are required for the time-of-day-dependent regulation of anxiety-like behaviors. We identify suprachiasmatic nucleus circadian oscillatory protein (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.

Assessing the effects of stress on feeding behaviors in laboratory mice

“…Assessing behaviors in the dark cycle is more physiologically relevant for feeding and minimizes stresses associated with the external environment and fasting, which impose sex-specific effects in mice and humans (described above). However, reported effects of diurnal factors on anxiety-like behavior are inconsistent, and are sex and assay dependent ( Richetto et al, 2019 ; Nakano et al, 2016 ). Here, we found that performing the NSF assay at the start of the dark cycle promoted hyperphagic responses in both sexes.…”

Influence of diurnal phase on behavioral tests of sensorimotor performance, anxiety, learning and memory in mice

“…However, few studies explore anxiety across time of day 16 . Previous studies provide evidence that the expression of suprachiasmatic nucleus circadian oscillatory protein (SCOP) in the basolateral amygdala plays a key role in generating circadian rhythmicity in anxiety-like behavior 17 . Other studies show melatonin is involved in the anxiety response of diurnal and nocturnal species 18 .…”

Fine-Tuning Circadian Rhythms: The Importance of Bmal1 Expression in the Ventral Forebrain

“…Pioneered by McClung et al the contribution of local clocks in the ventral tegmental area and nucleus accumbens, which constitute the mesolimbic dopaminergic pathway, in mood regulation has been well-characterized (McClung et al, 2005 ; Roybal et al, 2007 ; Mukherjee et al, 2010 ; Spencer et al, 2013 ; Chung et al, 2014 ). More recently, Shimizu et al reported that the suprachiasmatic nucleus circadian oscillatory protein (SCOP) mediates the circadian regulation of long-term memory formation by local clocks in the hippocampus (Shimizu et al, 2016 ), and Nakano et al, found that the same molecule regulates the circadian expression of anxiety-like behavior under the control of local clocks in the basolateral amygdala (Nakano et al, 2016 ). On another front, Yu et al reported that Bmal1 -dependent local clock in histaminergic neurons of tuberomammillary nucleus (TMN) regulate sleep architecture, likely via transcriptional control of the histidine decarboxylase gene, which encodes a histamine-synthesizing enzyme, but is not involved in regulating circadian rhythms (Yu et al, 2014 ).…”

“…Cell type-specific manipulations of clock genes have clarified the roles of peripheral circadian clocks in a variety of tissues (McDearmon et al, 2006 ; Storch et al, 2007 ; Lamia et al, 2008 ; Westgate et al, 2008 ; Dibner et al, 2010 ; Marcheva et al, 2010 ; Sadacca et al, 2011 ; Fustin et al, 2012 ; Paschos et al, 2012 ; Nguyen et al, 2013 ; Gibbs et al, 2014 ; Jacobi et al, 2015 ; Xie et al, 2015 ; Dudek et al, 2016 ; Xu et al, 2016 ). By contrast, knowledge of the physiological roles of brain clocks in extra-SCN regions remains limited (Roybal et al, 2007 ; Mukherjee et al, 2010 ; Mieda and Sakurai, 2011 ; Spencer et al, 2013 ; Yu et al, 2014 ; Nakano et al, 2016 ; Orozco-Solis et al, 2016 ; Shimizu et al, 2016 ).…”