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

Mulder CK, Papantoniou C, Gerkema MP, Van Der Zee EA - Chronobiol. Int. (2014)

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.

View Article: PubMed Central - PubMed

Affiliation: Department of Molecular Neurobiology and.

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.

Show MeSH
Average daily TPL performance after abrupt LEO and FEO phase-shifts. After testing on day 3, in the beginning of the subjective dark phase, a 3h light pulse (400–800 lux) was applied according to an Aschoff type II protocol. After performance recovered, food was delayed by 6 hours (after testing on day 8). After performance recovered, food was advanced by 6h on day 11. Days are shown on the x-axis (non-shaded days indicate testing in LD; shaded days indicate testing in DD). The grey area around the black performance curve indicates SEM. Vertical lines indicate the interventions. Chance level is indicated by the horizontal line. Daily session-specific performance is shown in bar charts underneath the average daily performance graph (x-axis days are aligned; vertical height of the bars represent relative performance).
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f3: Average daily TPL performance after abrupt LEO and FEO phase-shifts. After testing on day 3, in the beginning of the subjective dark phase, a 3h light pulse (400–800 lux) was applied according to an Aschoff type II protocol. After performance recovered, food was delayed by 6 hours (after testing on day 8). After performance recovered, food was advanced by 6h on day 11. Days are shown on the x-axis (non-shaded days indicate testing in LD; shaded days indicate testing in DD). The grey area around the black performance curve indicates SEM. Vertical lines indicate the interventions. Chance level is indicated by the horizontal line. Daily session-specific performance is shown in bar charts underneath the average daily performance graph (x-axis days are aligned; vertical height of the bars represent relative performance).

Mentions: Results are shown in Figure 3. Manipulations were performed on a cohort of seven mice, which had successfully mastered cTPL. High intensity light pulses can phase delay SCN/LEO mediated circadian rhythms when applied at the beginning of the dark phase. We applied a 3h light pulse of 400–800 lux, according to an Aschoff type II protocol (Albrecht et al., 2001). On day 2, lights went out on the regular time (ZT12). On following days, mice remained housed- and were tested in darkness (under a constant dim red light <1 lux measured at the bottom of the cages and the level of the mice in the TPL paradigm). After TPL testing on day 3, the light pulse was applied at the beginning of the subjective dark phase, from circadian time (CT) 12 to CT15. In agreement with the known mouse phase response curve (PRC; Comas et al., 2006), the light pulse induced a 2.5–3 h phase delay in the activity onset of the two HCC animals (the effect size was most clearly distinguishable in these animals because their behavioral rhythms were not influenced/masked by food deprivation and TPL testing procedures). The intervention resulted in a markedly decline in TPL performance lasting for 2–3 days. Daily performances were compared by two-tailed paired t-test. Compared to day 3, performance was dropped significantly on days 4 (p = 0.0004) and 5 (p = 0.0006), but was recovered on day 6 (p = 0.45). Next, a 6 h food delay was performed. Instead of receiving food at CT10.5, mice received food at CT16.5, after TPL testing on day 8. Compared to day 8, this intervention resulted in a significant performance loss on day 9 (p = 0.0002), while performance was recovered on day 10 (p = 0.17). Subsequently a food advance was performed. Instead of receiving food at CT10.5, mice received food at CT4.5, after the first TPL test session on day 11 (test sessions 2 and 3 omitted). Compared to day 10 (day 11 was an incomplete test day), this resulted in a significant performance loss on days 12 (p = 0.008) and 13 (p = 0.008), while performance was recovered on day 14 (p = 0.60). Although test sessions 2 and 3 were omitted on day 11, performance loss does not normally occur after omitting multiple sessions or even complete test days (Mulder et al., 2013c). Daily session-specific performance is shown below the average daily performance graph, in relative bar charts (Figure 3). The light pulse mainly affected performance in sessions 1 and 3 on day 4, while affecting all three daily sessions on day 5. The food delay mainly affected performance only in session 2 on day 9 (all mice wrongly avoided the right-side location instead of the middle location, i.e. mice reacted as if the TOD was later, closer to the third session TOD). The food advance mainly affected performance in session 2 on day 12 (all mice wrongly avoided the left-side location instead of the middle, i.e. mice reacted as if the TOD was earlier, closer to the first session TOD) and session 1 on day 13 (all mice wrongly avoided the right-side location instead of the left-side location, i.e. mice reacted as if the TOD was later, closer to the third session TOD).Figure 3.


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

Mulder CK, Papantoniou C, Gerkema MP, Van Der Zee EA - Chronobiol. Int. (2014)

Average daily TPL performance after abrupt LEO and FEO phase-shifts. After testing on day 3, in the beginning of the subjective dark phase, a 3h light pulse (400–800 lux) was applied according to an Aschoff type II protocol. After performance recovered, food was delayed by 6 hours (after testing on day 8). After performance recovered, food was advanced by 6h on day 11. Days are shown on the x-axis (non-shaded days indicate testing in LD; shaded days indicate testing in DD). The grey area around the black performance curve indicates SEM. Vertical lines indicate the interventions. Chance level is indicated by the horizontal line. Daily session-specific performance is shown in bar charts underneath the average daily performance graph (x-axis days are aligned; vertical height of the bars represent relative performance).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4219850&req=5

f3: Average daily TPL performance after abrupt LEO and FEO phase-shifts. After testing on day 3, in the beginning of the subjective dark phase, a 3h light pulse (400–800 lux) was applied according to an Aschoff type II protocol. After performance recovered, food was delayed by 6 hours (after testing on day 8). After performance recovered, food was advanced by 6h on day 11. Days are shown on the x-axis (non-shaded days indicate testing in LD; shaded days indicate testing in DD). The grey area around the black performance curve indicates SEM. Vertical lines indicate the interventions. Chance level is indicated by the horizontal line. Daily session-specific performance is shown in bar charts underneath the average daily performance graph (x-axis days are aligned; vertical height of the bars represent relative performance).
Mentions: Results are shown in Figure 3. Manipulations were performed on a cohort of seven mice, which had successfully mastered cTPL. High intensity light pulses can phase delay SCN/LEO mediated circadian rhythms when applied at the beginning of the dark phase. We applied a 3h light pulse of 400–800 lux, according to an Aschoff type II protocol (Albrecht et al., 2001). On day 2, lights went out on the regular time (ZT12). On following days, mice remained housed- and were tested in darkness (under a constant dim red light <1 lux measured at the bottom of the cages and the level of the mice in the TPL paradigm). After TPL testing on day 3, the light pulse was applied at the beginning of the subjective dark phase, from circadian time (CT) 12 to CT15. In agreement with the known mouse phase response curve (PRC; Comas et al., 2006), the light pulse induced a 2.5–3 h phase delay in the activity onset of the two HCC animals (the effect size was most clearly distinguishable in these animals because their behavioral rhythms were not influenced/masked by food deprivation and TPL testing procedures). The intervention resulted in a markedly decline in TPL performance lasting for 2–3 days. Daily performances were compared by two-tailed paired t-test. Compared to day 3, performance was dropped significantly on days 4 (p = 0.0004) and 5 (p = 0.0006), but was recovered on day 6 (p = 0.45). Next, a 6 h food delay was performed. Instead of receiving food at CT10.5, mice received food at CT16.5, after TPL testing on day 8. Compared to day 8, this intervention resulted in a significant performance loss on day 9 (p = 0.0002), while performance was recovered on day 10 (p = 0.17). Subsequently a food advance was performed. Instead of receiving food at CT10.5, mice received food at CT4.5, after the first TPL test session on day 11 (test sessions 2 and 3 omitted). Compared to day 10 (day 11 was an incomplete test day), this resulted in a significant performance loss on days 12 (p = 0.008) and 13 (p = 0.008), while performance was recovered on day 14 (p = 0.60). Although test sessions 2 and 3 were omitted on day 11, performance loss does not normally occur after omitting multiple sessions or even complete test days (Mulder et al., 2013c). Daily session-specific performance is shown below the average daily performance graph, in relative bar charts (Figure 3). The light pulse mainly affected performance in sessions 1 and 3 on day 4, while affecting all three daily sessions on day 5. The food delay mainly affected performance only in session 2 on day 9 (all mice wrongly avoided the right-side location instead of the middle location, i.e. mice reacted as if the TOD was later, closer to the third session TOD). The food advance mainly affected performance in session 2 on day 12 (all mice wrongly avoided the left-side location instead of the middle, i.e. mice reacted as if the TOD was earlier, closer to the first session TOD) and session 1 on day 13 (all mice wrongly avoided the right-side location instead of the left-side location, i.e. mice reacted as if the TOD was later, closer to the third session TOD).Figure 3.

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.

View Article: PubMed Central - PubMed

Affiliation: Department of Molecular Neurobiology and.

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.

Show MeSH