Neither the SCN nor the adrenals are required for circadian time-place learning in mice.
Bottom Line: 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.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.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.
Affiliation: Department of Molecular Neurobiology and.
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.
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Mentions: Results are shown in Figure 5(a) (pooled data from the two batches). During the first habituation step (days 1 through 4, not shown), mice could freely explore the three baited locations. No significant preference for a single (first choice) location was found (chi-square p = 0.93, no significant group/batch differences). During the second habituation step (days 5 through 7, test situation with target locations baited; non-target location unbaited without foot-shock delivery), performance of SHAM and SCNx mice did not significantly differ from chance level (two-tailed one-sample t-test: p = 0.10 and p = 0.17 respectively), nor from each other (two-tailed unpaired t-test: p = 0.80). On day 8, mice were habituated to first time foot-shock exposure (see materials and methods, excluded from analyses). During the third habituation step (days 9 and 10, test situation with target locations baited, non-target location unbaited with foot-shock delivery), both SHAM and SCNx mice significantly learned to avoid the non-target location, showing performance significantly different from (above) chance level (p < 0.001 for both SHAM and SCNx mice), with no significant difference between the groups (p = 0.34). High performance is common in this habituation step because mice can identify the non-target/target location(s) based on sight/smell of the absence/presence of food. No significant differences were found between the two batches in any of the habituation steps.Figure 5.