The role of spatial and temporal information in learning interval time-place tasks

In time-place learning (TPL) paradigms animals are thought to form tripartite memory codes consisting of the spatiotemporal characteristics of biologically significant events. In Phase I, rats were trained on a modified TPL task in which either the spatial or temporal component was constant, while the other component varied randomly. If the memory codes are tripartite then when one aspect of the code is random the rats should have difficulty learning the constant aspect of the code. However, rats that were trained with a fixed spatial sequence of food availability and a random duration did in fact learn the task. Rats that were trained with a fixed duration and a random sequence did not learn the task. In Phase II all rats were placed on a TPL task in which food availability was contingent upon both spatial and temporal information. According to the tripartite theory, prior knowledge of either aspect of the code should have little effect on the acquisition of the task. The rats that received fixed spatial training learned the task relatively more quickly. The use of bipartite, rather than tripartite codes, is better able to explain the results of the current study.     

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

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.     

Circadian time-place learning in mice depends on Cry genes

Endogenous biological clocks allow organisms to anticipate daily environmental cycles. The ability to achieve time-place associations is key to the survival and reproductive success of animals. The ability to link the location of a stimulus (usually food) with time of day has been coined time-place learning, but its circadian nature was only shown in honeybees and birds. So far, an unambiguous circadian time-place-learning paradigm for mammals is lacking. We studied whether expression of the clock gene Cryptochrome (Cry), crucial for circadian timing, is a prerequisite for time-place learning. Time-place learning in mice was achieved by developing a novel paradigm in which food reward at specific times of day was counterbalanced by the penalty of receiving a mild footshock. Mice lacking the core clock genes Cry1 and Cry2 (Cry double knockout mice; Cry1(-/-)Cry2(-/-)) learned to avoid unpleasant sensory experiences (mild footshock) and could locate a food reward in a spatial learning task (place preference). These mice failed, however, to learn time-place associations. This specific learning and memory deficit shows that a Cry-gene dependent circadian timing system underlies the utilization of time of day information. These results reveal a new functional role of the mammalian circadian timing system.     

Hippocampal and striatal dependent navigation: Sex differences are limited to acquisition

Estrogen has been demonstrated to enhance the use of hippocampal-based place learning while reducing the use of striatal-based motor-response strategy (Korol, D.L., Malin, E.L., Borden, K.A., Busby, R.A., & Couper-Leo, J. (2004). Shifts in preferred learning strategy across the estrous cycle in female rats. Horm. Behav. 45, 330–338). Previous research has focused on task acquisition and the switch from a place to motor-response navigation with training. The current paradigm allowed an examination of the interplay between these two systems by having well-trained animals switch strategies “on demand.” Female and male Sprague–Dawley rats were taught a motor-response task on a plus maze. The rats were then introduced to a place task and taught to switch, by cue, from the motor-response to place strategy. Finally, the rats were trained to continuously alternate between place and motor-responses strategies. The maze configuration allowed for an analysis of cooperative choices (both strategies result in the same goal arm), competitive choices (both strategies result in different goal arms), and single strategy choices (can only use the motor-response strategy). The results indicate that sex and estrogen-related effects on navigation strategy are limited to the initial stages of learning a task. The role of sex and estrogen is diminished once the task is well learned, and presumably, the relative involvement of the hippocampal and striatal systems is established.     

Evidence for an alternation strategy in time-place learning

Many different conclusions concerning what type of mechanism rats use to solve a daily time-place task have emerged in the literature. The purpose of this study was to test three competing explanations of time-place discrimination. Rats (n = 10) were tested twice daily in a T-maze, separated by approximately 7 h. Food was available at one location in the morning and another location in the afternoon. After the rats learned to visit each location at the appropriate time, tests were omitted to evaluate whether the rats were utilizing time-of-day (i.e., a circadian oscillator) or an alternation strategy (i.e., visiting a correct location is a cue to visit the next location). Performance on this test was significantly lower than chance, ruling out the use of time-of-day. A phase advance of the light cycle was conducted to test the alternation strategy and timing with respect to the light cycle (i.e., an interval timer). There was no difference between probe and baseline performance. These results suggest that the rats used an alternation strategy to meet the temporal and spatial contingencies in the time-place task.     

How rats process spatiotemporal information in the face of distraction

How rats process spatiotemporal information in the face of distraction was assessed. Rats were trained on a time-place learning task in which the location of food availability depended on the amount of time elapsed since the beginning of the training session. In each training session each of four levers provided food pellets for 5 min on an intermittent schedule. In probe sessions interspersed with the final training sessions, the rats were presented with a second highly preferred food source-a piece of cheese-at various times into the session. Rats choose the correct lever after the cheese distraction, but it appeared that their internal clock had stopped during the cheese consumption period. Thus rats' internal clock, like that of pigeons, displays the properties of 'stop', 'reset', and 'restart'. Rat-pigeon differences in timing processes may be restricted to circadian or time of day timing. Present results also suggest that rats process spatial and temporal information separately.     

Rats’ learning of a new motor skill: Insight into the evolution of motor sequence learning

Recent behavioral and neural evidence has suggested that ethologically relevant sub-movements (movement primitives) are used by primates for more complex motor skill learning. These primitives include extending the hand, grasping an object, and holding food while moving it toward the mouth. In prior experiments with rats performing a reach-to-grasp-food task, we observed that especially during early task learning, rats appeared to have movement primitives similar to those seen in primates. Unlike primates, however, during task learning the rats performed these sub-movements in a disordered manner not seen in humans or macaques, e.g. with the rat chewing before placing the food pellet in its mouth. Here, in two experiments, we tested the hypothesis that for rats, learning this ecologically relevant skill involved learning to concatenate the sub-movements in the correct order. The results confirmed our initial observations, and suggested that several aspects of forepaw/hand use, taken for granted in primate studies, must be learned by rats to perform a logically connected and seemingly ecologically important series of sub-movements. We discuss our results from a comparative and evolutionary perspective.     

Interval time-place learning by rats: varying reinforcement contingencies

Two experiments with rats were conducted to study interval time-place learning when the spatiotemporal contingencies of food availability were more similar to those likely to be encountered in natural environments, than those employed in prior research. In Experiment 1, food was always available on three levers on a variable ratio (VR) 35 schedule. A VR8 schedule was in effect on Lever 1 for 5 min, then on Lever 2 for 5 min, and so forth. While rats learned to restrict the majority of their responding to the lever that provided the highest density of reinforcement, they seemed to rely on a win-stay/lose-shift strategy rather than a timing strategy. In Experiment 2, the four levers provided food on variable ratios of 15, 8, 15, and 30, each for 3 min. As expected the rats learned these contingencies. A novel finding was that the rats had a spike in response rate immediately following a change from a higher to lower reinforcement density. It is concluded that rats exposed to spatiotemporal contingencies behave so as to maximize the rate of obtained reinforcement.     

Evidence for time-place learning in the Morris water maze without food restriction but with increased response cost

Time-place learning is the ability to distinguish between resources that vary in location at different times of day. Only one previous report has demonstrated successful time-place learning without using food as reward. In this experiment, satiated rats failed to form time-place discriminations in a Morris water maze while food deprived rats did, leading to the conclusion that food system activation is necessary for time-place learning. However, in addition to food system activation, response cost was also increased, which previously has been demonstrated to be effective in allowing the formation of time-place discriminations. The purpose of these two experiments is to test whether food system activation or heightened response cost allowed for time-place learning in the Morris water maze. In the first experiment, we replicate the failure to find time-place discriminations in the Morris water maze without food restriction and without increased response cost. In the second experiment, we found that increased response cost without food restriction was effective in allowing the formation of a time-place discrimination. The implications of this result are discussed in light of the timing mechanism used for time-place discriminations, the nature of the response cost, and the event-time-place tripartite association.     

Behavioral analysis of consequences of chronic blockade of NMDA-type glutamate receptors in the early postnatal period in rats

In view of the hypothesis that glutamatergic dysfunction of brain can underlie the negative symptoms of schizophrenia (including cognitive deficit), the aim of this study was to develop a model of cognitive impairment in Wistar male rats after administration of a noncompetitive NMDA-receptor antagonist in early postnatal period. Rat pups were daily subcutaneously injected with 0.05 mg/kg MK-801 on postnatal days 7-49. On the 27th and 28th days 24 h after the last previous injection, the MK-801-treated rats demonstrated lower spontaneous locomotor and exploratory activity in comparison with saline control, however, they retained the reaction of hyperlocomotion which developed immediately after the MK-801 administration. In these rats, the anxiety level in the elevated plus-maze (on the 40th postnatal day) was found to be decreased, and the spatial learning in food rewarded task was negatively affected (on the 50th-54th days). It is suggested that impairment of the input of sensory information and its correct assessment by the animals can be associated with the early neonatal blockade of NMDA glutamate receptors.     

慢性束缚应激对SD和Wistar大鼠学习记忆能力的影响

目的探讨慢性束缚应激对Wistar、SD两种品系大鼠学习记忆能力的影响,为应激模型中实验动物的选择提供依据。方法对两种品系大鼠(Wistar、SD)采用每天束缚10 h,束缚28 d建立慢性应激模型。采用物体认知新物体识别实验和Morris水迷宫空间学习、工作记忆行为学检测方法,观察束缚应激对两种品系实验动物学习记忆能力的影响。结果束缚28 d后,物体识别实验中,Wistar、SD模型组的辨别指数(discrimination index,DI)均低于对照组,但只有SD两组间差异存在显著性(P0.05);水迷宫空间学习阶段,SD模型组潜伏期高于对照组,第5天差异有显著性(P0.05),而Wistar模型组与对照组间的潜伏期没有差异;水迷宫工作记忆阶段,SD大鼠模型组与正常组比较,潜伏期显著增加(P0.05),Wistar模型大鼠的潜伏期与对照组比较没有显著差异。结论新物体识别实验和水迷宫实验,这两种反应动物不同学习记忆能力的行为学实验结果都表明,慢性束缚应激(10 h,28 d)对SD大鼠学习记忆能力的损伤较Wistar大鼠明显。SD大鼠可能更适合作为慢性应激所致学习记忆损伤动物模型。     

Evolution of learned strategy choice in a frequency-dependent game

In frequency-dependent games, strategy choice may be innate or learned. While experimental evidence in the producer-scrounger game suggests that learned strategy choice may be common, a recent theoretical analysis demonstrated that learning by only some individuals prevents learning from evolving in others. Here, however, we model learning explicitly, and demonstrate that learning can easily evolve in the whole population. We used an agent-based evolutionary simulation of the producer-scrounger game to test the success of two general learning rules for strategy choice. We found that learning was eventually acquired by all individuals under a sufficient degree of environmental fluctuation, and when players were phenotypically asymmetric. In the absence of sufficient environmental change or phenotypic asymmetries, the correct target for learning seems to be confounded by game dynamics, and innate strategy choice is likely to be fixed in the population. The results demonstrate that under biologically plausible conditions, learning can easily evolve in the whole population and that phenotypic asymmetry is important for the evolution of learned strategy choice, especially in a stable or mildly changing environment.     

A simple spatial alternation task for assessing memory function in zebrafish

A series of studies was initiated to examine learning and memory function in the zebrafish (Danio rerio) by using a simple spatial alternation paradigm for a food reward. Fish were fed on alternating sides of a divided fish tank, with a red card displayed on one side serving as a visual means of orientation. Although responses were recorded at cue (light tap on the tank), 5 s after cue (as food was delivered), and 5 s after food delivery, the learning test was choice of a correct side of the tank to receive food. Therefore, an accurate level of an animal's achievement of the spatial task was represented by responses at food delivery. Data collected from 11 separate experiments indicated that zebrafish learned to alternate for a food reward. Further, statistical analysis showed that the zebrafish learned the task in the first half of the experiment as exhibited by a calculated t1/2 of 13.9 trials. Zebrafish could recall the task after a short period of 10 days with no testing. The alternating behavior was extinguished by withholding the food reward. Thus, the spatial alternation task can be learned easily by zebrafish, and may be useful in addressing learning and memory functions in vertebrate animals using zebrafish as a model organism.     

A test of time-place learning in a cichlid fish

This paper presents a test of time-place learning in fish. Convict cichlids, Cichlasoma nigrofasciatum, were offered food several times a day for 10–30 consecutive days. A signal was given 1 min before each food presentation. If the food was always delivered in the same corner of the aquarium, the fish spent 66% of their time in that corner after the signal was given. But if the food was given in different corners throughout the day, each corner being associated with a specific daily time, the fish failed to show preference for the target corner, even after 30 days. Instead they learned which corners yielded food at any time of the day and visited these corners successively after the feeding signal was given. Failure to associate time and place may have been caused by a low cost of travel between corners, a limited number of rewards each day, and / or interference from learning the signal-food association.     

Time–Place Learning Based on Food but not on Predation Risk in a Fish, the Inanga (Galaxias maculatus)

Time–place learning, or the ability to learn to be in different places at different times of day, is already known to occur in response to daily spatio-temporal patterns of food availability. However, the ability to learn daily patterns of predation risk and move between areas at the right time of day in order to avoid predation has never been tested. This study asked whether inangas, Galaxias maculatus , are capable of time–place learning based on food availability only, predation risk only, or the antagonistic combination of food availability and predation risk. Shoals of five inangas were kept in aquaria partially divided into a right and left section. Every day they were exposed to a stimulus on one side in the morning and on the other side in the afternoon. Depending on the experiment, the stimulus could be two deliveries of food, two simulated heron strikes, or both of the above within the same hour. After 14 d the stimuli were not given and the position of the fish was noted in both the morning and the afternoon. The majority of the fish learned to switch sides at the correct daily time in order to get food, but they remained on the same side at both daily times in response to either predation risk alone or the combination of predation risk and food. It seems that the potential for time–place learning based on predation risk is less than that based on food, and that predation risk can even curtail the expression of time–place learning based on food. Fish may resort to other tactics, such as shoaling and reduced movement, in response to predation risk. Daily habitat shifts could still be present in nature and rooted in the avoidance of predation, but instead of being the direct result of learning they would be mostly innate.     

Breakfast in the nook and dinner in the dining room: time-of-day discrimination in rats

Four studies were conducted which demonstrate that most (63%) male Sprague-Dawley rats can attain criterion, nine correct choices over ten consecutive trials, on a time-of-day discrimination in an elevated T-maze, but that the task is relatively difficult. The discrimination required that the rats go to one goal arm during a morning session and the other in an afternoon session. The sessions always began at the same time and were at least 6 h apart. A larger proportion of rats attained criterion and required fewer trials when the discriminative cue was a maze insert providing visual and tactile stimulation (0.72), orientation and position of the maze in the room (0.88), or the rats were required to always make the same left or right turn (0.94). Also, once criterion was attained, rats trained on time-of-day discrimination only made about 70% correct choices with continued training. Housing the rats with continuous light, all laboratory noises masked with white noise, and a random feeding schedule did not prevent them from acquiring the time-place discrimination. Testing the rats with a random number of trials during morning and afternoon sessions and with added or omitted sessions revealed that the rats did not use response or session alternation strategies to perform the discrimination. Also, the particular experimenter administering the morning or afternoon sessions did not serve as a cue for the discrimination. The relative difficulty of the task suggests that time of day does not normally function as a discriminative stimulus for choices, but probably as a contextual stimulus. Further, performance of the task in the absence of time-of-day cues suggests that the discrimination is based on event memory combined with an internal timing mechanism.     

1439 MHz pulsed TDMA fields affect performance of rats in a T-maze task only when body temperature is elevated

This study sought to clarify the effects of exposure to electromagnetic waves (EMW) used in cellular phones on learning and memory processes. Sprague-Dawley rats were exposed for either 1 h daily for 4 days or for 4 weeks to a pulsed 1439 MHz time division multiple access (TDMA) field in a carousel type exposure system. At the brain, average specific absorption rate (SAR) was 7.5 W/kg, and the whole body average SAR was 1.7 W/kg. Other subjects were exposed at the brain average SAR of 25 W/kg and the whole body average SAR of 5.7 W/kg for 45 min daily for 4 days. Learning and memory were evaluated by reversal learning in a food rewarded T-maze, in which rats learned the location of food (right or left) by using environmental cues. The animals exposed to EMW with the brain average SAR of 25 W/kg for 4 days showed statistically significant decreases in the transition in number of correct choices in the reversal task, compared to sham exposed or cage control animals. However, rats exposed to the brain average SAR of 7.5 W/kg for either 4 days or for 4 weeks showed no T-maze performance impairments. Intraperitoneal temperatures, as measured by a fiber optic thermometer, increased in the rats exposed to the brain average SAR of 25 W/kg but remained the same for the brain average SAR of 7.5 W/kg. The SAR of a standard cellular phone is restricted to a maximum of 2 W/kg averaged over 10 g tissue. These results suggest that the exposure to a TDMA field at levels about four times stronger than emitted by cellular phones does not affect the learning and memory processes when there are no thermal effects.     

Sex and estrous cycle differences in immediate early gene activation in the hippocampus and the dorsal striatum after the cue competition task

The hippocampus and dorsal striatum are important structures involved in place and response learning strategies respectively. Both sex and estrous cycle phase differences in learning strategy preference exist following cue competition paradigms. Furthermore, significant effects of sex and learning strategy on hippocampal neural plasticity have been reported. However, associations between learning strategy and immediate early gene (IEG) expression in the hippocampus and dorsal striatum are not completely understood. In the current study we investigated the effects of sex and estrous cycle phase on strategy choice and IEG expression in the hippocampus and dorsal striatum of rats following cue competition training in the Morris water maze. We found that proestrous rats were more likely to choose a place strategy than non-proestrous or male rats. Although male cue strategy users travelled greater distances than the other groups on the first day of training, there were no other sex or strategy differences in the ability to reach a hidden or a visible platform. Female place strategy users exhibited greater zif268 expression and male place strategy users exhibited greater cFos expression compared to all other groups in CA3. Furthermore, cue strategy users had greater expression of cFos in the dorsal striatum than place strategy users. Shorter distances to reach a visible platform were associated with less activation of cFos in CA3 and CA1 of male place strategy users. Our findings indicate multiple differences in brain activation with sex and strategy use, despite limited behavioral differences between the sexes on this cue competition paradigm.     

Time-place learning in individually reared angelfish, but not in pearl cichlid

Time-place learning based on food association was investigated in the cichlids angelfish (Pterophyllum scalare) and pearl cichlid (Geophagus brasiliensis) reared in isolation, therefore eliminating social influence on foraging. During a 30-day period, food was placed in one side of the aquarium (containing three compartments) in the morning and in the opposite side in the afternoon. Learning was inferred by the number of correct side choices of all fish in each day of test (15th and 30th). During the test day fish were not fed. The angelfish learned to switch sides at the correct day period in order to get food, suggesting this species has time-place learning ability when individually reared. On the other hand, the same was not observed for pearl cichlid.     

Diurnal variations in learning performance in chickens

Diurnal variations in the learning performance of young chicks were investigated using a visual discrimination task which requires birds to discrminate grains from a background of pebbles. Chicks accustomed to receiving fresh food daily in the morning were found to learn well during the day, in that they pecked almost exclusively at grains; but during the night they pecked indiscriminately at grains and pebbles. This occurred even though food was available ad libitum. Chicks accustomed to receiving fresh food daily in the evening learnt the task during the day, and also late at night. Thus the shape of the performance cycle depends in part on environmental factors. Other factors, such as activity, which may contribute to, or co-vary with, this variation in learning performance were investigated.