Forced Desynchrony Reveals Independent Contributions of Suprachiasmatic Oscillators to the Daily Plasma Corticosterone Rhythm in Male Rats

Abstract

The suprachiasmatic nucleus (SCN) is required for the daily rhythm of plasma glucocorticoids; however, the independent contributions from oscillators within the different subregions of the SCN to the glucocorticoid rhythm remain unclear. Here, we use genetically and neurologically intact, forced desynchronized rats to test the hypothesis that the daily rhythm of the glucocorticoid, corticosterone, is regulated by both light responsive and light-dissociated circadian oscillators in the ventrolateral (vl-) and dorsomedial (dm-) SCN, respectively. We show that when the vlSCN and dmSCN are in maximum phase misalignment, the peak of the plasma corticosterone rhythm is shifted and the amplitude reduced; whereas, the peak of the plasma adrenocorticotropic hormone (ACTH) rhythm is also reduced, the phase is dissociated from that of the corticosterone rhythm. These data support previous studies suggesting an ACTH-independent pathway contributes to the corticosterone rhythm. To determine if either SCN subregion independently regulates corticosterone through the sympathetic nervous system, we compared unilateral adrenalectomized, desynchronized rats that had undergone either transection of the thoracic splanchnic nerve or sham transection to the remaining adrenal. Splanchnicectomy reduced and phase advanced the peak of both the corticosterone and ACTH rhythms. These data suggest that both the vlSCN and dmSCN contribute to the corticosterone rhythm by both reducing plasma ACTH and differentially regulating plasma corticosterone through an ACTH- and sympathetic nervous system-independent pathway.

Collective timekeeping among cells of the master circadian clock

“…The functional roles of projections from distinct SCN regions are far from fully understood. Thus far, research indicates that both SCN compartments influence rhythms in downstream targets, yet there are differences in the role of outputs from different SCN regions (Butler, et al 2012; Evans et al 2015; Kalsbeek, et al 2010; Lee, et al 2009; Schwartz, et al 2009; Smarr, et al 2012; Wotus, et al 2013; Yan, et al 2005; Zhou and Cheng 2005). One emerging theme is that the SCN shell appears to set the phase of downstream tissues; however, both SCN shell and core neurons provide signals to downstream tissues that can influence their rhythms.…”

In synch but not in step: Circadian clock circuits regulating plasticity in daily rhythms

“…Importantly, differential gene expression in these SCN regions appears to persist temporarily after release into DD, arguing against a pure masking effect by light and darkness. To date, the forced desynchrony paradigm has been used to provide new insight into the function of outputs specifically produced by SCN shell and core compartments (Lee et al, 2009, Schwartz et al, 2009, Smarr et al, 2012, Wotus et al, 2013), as well as the propagation of resetting signals within the SCN network (Schwartz et al, 2010). It remains unclear if analogous behavior is observed in other species, but if the rat is unique in its expression of this behavior, then this may provide an interesting comparative approach for studying circuit properties that enable this form of plasticity.…”

Fragmentation of Rapid Eye Movement and Nonrapid Eye Movement Sleep without Total Sleep Loss Impairs Hippocampus-Dependent Fear Memory Consolidation

“…Among these rhythms, the release of corticosterone is disrupted during misaligned days in the forced desynchronized rat. 15 Post-training increases in corticosterone levels have been associated with increased consolidation in cued and contextual fear memory. 39,40 Thus, impaired contextual fear memory consolidation during LD22 misaligned phases could reflect an inability to increase glucocorticoid release.…”

“…Misaligned LD22 rats have intermediate levels of corticosterone throughout the LD cycle, and compared to aligned LD22 rats, they have higher levels during the light phase and lower levels during the dark phase. 15 Despite these contrasting differences in each phase, misaligned animals trained either during the light or dark phases showed impaired memory consolidation relative to aligned animals. Nevertheless, the possibility remains that circadian misaligned animals are unable to mount a glucocorticoid increase that favors memory consolidation.…”

“…However, forced desynchronized rats show desynchrony in other circadian rhythms that could be responsible for memory deficits. 5,9,15,16 To determine whether memory deficits in LD22 misaligned animals are associated specifically with our observed fragmentation of NREM and REM sleep, we repeated our contextual fear conditioning experiments in all three experimental groups while simultaneously recording the vigilance states with ECoG electrodes after training for each animal. We plotted a survival curve and fitted an exponential decay curve for each animal and sleep stage during the light phase one day after training.…”