Neither the SCN nor the adrenals are required for circadian time-place learning in mice

Abstract

During Time-Place Learning (TPL), animals link biological significant events (e.g. encountering predators, food, mates) with the location and time of occurrence in the environment. This allows animals to anticipate which locations to visit or avoid based on previous experience and knowledge of the current time of day. The TPL task applied in this study consists of three daily sessions in a three-arm maze, with a food reward at the end of each arm. During each session, mice should avoid one specific arm to avoid a foot-shock. We previously demonstrated that, rather than using external cue-based strategies, mice use an internal clock (circadian strategy) for TPL, referred to as circadian TPL (cTPL). It is unknown in which brain region(s) or peripheral organ(s) the consulted clock underlying cTPL resides. Three candidates were examined in this study: (a) the suprachiasmatic nucleus (SCN), a light entrainable oscillator (LEO) and considered the master circadian clock in the brain, (b) the food entrainable oscillator (FEO), entrained by restricted food availability, and (c) the adrenal glands, harboring an important peripheral oscillator. cTPL performance should be affected if the underlying oscillator system is abruptly phase-shifted. Therefore, we first investigated cTPL sensitivity to abrupt light and food shifts. Next we investigated cTPL in SCN-lesioned- and adrenalectomized mice. Abrupt FEO phase-shifts (induced by advancing and delaying feeding time) affected TPL performance in specific test sessions while a LEO phase-shift (induced by a light pulse) more severely affected TPL performance in all three daily test sessions. SCN-lesioned mice showed no TPL deficiencies compared to SHAM-lesioned mice. Moreover, both SHAM- and SCN-lesioned mice showed unaffected cTPL performance when re-tested after bilateral adrenalectomy. We conclude that, although cTPL is sensitive to timing manipulations with light as well as food, neither the SCN nor the adrenals are required for cTPL in mice.

Time-Restricted Feeding Improves Circadian Dysfunction as well as Motor Symptoms in the Q175 Mouse Model of Huntington’s Disease

“…While lighting conditions are a critical environmental input to this timing system, a body of recent work has lead us to appreciate that the feed/fast cycle is also a powerful regulators of the circadian system (Hamaguchi et al, 2015). While progressive, age-related SCN dysfunction has been reported in HD mouse models (Bartlett et al, 2016), a time-restricted feeding (TRF) regimen promises therapeutic potential and can benefit even SCN-lesioned mice (Hara et al, 2001; Mulder et al, 2014). For example, mice under TRF consume equivalent calories from a high-fat diet as those with ad libitum (ad lib) access yet are protected against obesity, hyperinsulinemia, and inflammation and have improved motor coordination (Hatori et al, 2012).…”

Meal frequency and timing in health and disease

“…Missense mutation in circadian clock component Per1 has been shown to affect eating patterns in mice (21). However, the presence of intact food anticipatory activity in SCN ablated rodents or those lacking functional circadian oscillator genes points to yet-unidentified genes and circuits in eating-pattern determination (82,83). Humans are highly heterogeneous with regard to their genetic composition, epigenetic landscape, and the environmental factors to which they are exposed throughout life.…”

Time–place learning over a lifetime: absence of memory loss in trained old mice

“…This paradigm emulates the natural situation in which hungry animals seek food while different feeding locations can be predictably safe or unsafe to visit depending on the TOD. We have shown repeatedly that young wild-type mice readily acquire this paradigm and will structurally use a circadian strategy (Van der Zee et al 2008;Mulder et al 2013aMulder et al , 2014.…”