Research reportThe significance of circadian phase for performance on a reward-based learning task in hamsters
Introduction
A growing body of evidence demonstrates that circadian timekeeping can influence the processes of learning and memory. This comes from studies of both humans and animal models (see Ref. [12]). The ability to learn, remember, and then to modify current responses according to prior experience are fundamental attributes of animal behavior. In mammals, learning involves a complex set of steps that comprise sensory processing, acquisition, memory formation, memory retention (and extinction), and memory retrieval. Recent studies have begun to demonstrate that these processes may be differentially influenced by the animal's circadian rhythms or by the time of day.
An association between rhythmicity and learning has been demonstrated in three general ways. First, situations where circadian rhythms are disturbed are invariably linked with cognitive impairment. In humans, these include the aging process, shift work, transmeridian travel (jet lag), and disease. In animal models, the circadian disruptions produced by phase shifting the light–dark cycle result in impaired performance on passive avoidance tasks [6], [10], [27]. Age-related rhythm disturbances impair performance on a conditioned place preference (CPP) task in hamsters [1], and on a test of spatial learning in rats, memory retention is selectively impaired while the initial acquisition and recall are intact [7].
Second, processes underlying cognitive performance may be modulated over the day or a circadian cycle. Numerous studies have shown that optimal times of day exist for learning different tasks in humans and in animals [11], [15], [16], [20], [21], [29], [30]. In addition, retention deficits on numerous tasks recur at periodic intervals in rodents, suggesting that memory recall is subject to temporal modulation separately from acquisition and memory formation [18], [15], [16], [17], [29].
Finally, in some species and situations, the time of day or the phase of the circadian cycle may be an attribute of the environment that is learned. The ability to learn, remember, and respond according to the specific timing of events has an enormous adaptive significance [2], [9], [12], [13], [28]. Animal's ability to learn the timing of significant events is indicated by the anticipatory behavior of various animal species that are presented with timed rewards, e.g. temporally restricted feeding schedules [3], [8], [13], [23], [26].
Taken together, these studies show that essentially all steps in the learning process may be subject to temporal regulation. The degree to which each step is affected appears to depend on the species and the learning paradigm that is used. In addition, the time of day may be a feature that is learned along with other attributes such as location, context and value of the presented stimulus [12].
In our experiments, we have begun to address the extent to which the circadian rhythms influence each of these aspects of learning. Because reward is a strong motivator of learning and performance, we have focused on reward-associated learning. Using a CPP task, we have shown previously that the ability to learn associations between reward and context is impaired in hamsters with circadian rhythm disruption [1]. In rodents, and especially in hamsters, running wheel activity is highly rewarding. However, when given free access to a running wheel in constant environmental conditions, running activity is strongly restricted to the animal's subjective night time. This suggested two alternative hypotheses: (1) that the perceived reward value of the wheel changes through the day; or (2) that the response to reward is temporally restricted. Using brain stimulation reward (BSR), Yanofski et al. [31] showed that perceived reward value does not vary with circadian time in rats. However, we have found significant effects of BSR on hamster locomotor rhythms that are not detectable in rats (S.W. Cain et al., manuscript in preparation). Therefore, there may be important species differences in the connections among circadian and brain reward mechanisms.
Based on the first hypothesis, we predicted that the strength of the CPP that is developed by using timed wheel reward will vary with the animals' spontaneous patterns of behavior and wheel use. This was complicated by the fact that hamsters may be induced to use a wheel at times when spontaneous activity is low, i.e. a novel wheel can be potentially rewarding when the home cage wheel is not. This issue was addressed in the test of the second hypothesis from which we predicted that the acquisition of a place preference could occur any time that the relative reward value of the stimulus were high, but that the expression of the preference would still depend on the animal's natural pattern of locomotor activity.
Neither of the two hypotheses was supported by the results of these experiments. Instead, CPP expression was restricted to the temporal match between training and testing times. This indicates that the internal representation of time is a significant attribute of context even when time is not a discriminative cue.
Section snippets
Animals and activity recording
Forty-eight male Golden hamsters (Mesocricetus auratus) were obtained from Charles River Canada (Montreal, Quebec), and were between 80 and 90 days old at the beginning of the experiment. Animals were housed individually in polypropylene cages (22×20 cm) with free access to food, water, and a stainless steel running-wheel (17 cm in diameter). Wheel running activity was monitored continuously throughout the experiment using VitalView (MiniMitter Co., Inc., Sunriver, Oregon). Cages were kept
Results
The results from both experiments confirm the previously reported findings that the running wheel is rewarding and can condition a place preference in hamsters. In addition, they demonstrate that the hamster is capable of making associations and remembering the distinct differences between the two contexts used in these experiments.
Discussion
The predominant message that is communicated through these results is that the expression of a preference for a reward-associated context depends on whether the preference test is conducted at the same time of day (or circadian cycle) that the training occurred. Because all subjects were trained in the same manner at either time point, the results suggest that animals had learned during training, but did not behave as though they had learned unless the timing of the test approximated the time
Acknowledgements
Research reported in this paper and the preparation of this manuscript were supported by Natural Sciences and Engineering Research Council (NSERC) grants to M.R.R. (#RGPIN170040) and R.J.M. (#RGPIN183945) and a NSERC postgraduate scholarship to C.H.K.
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