Amphetamine disrupts both working and reference memories of rats trained in a radial maze

To assess the effects of amphetamine on working and reference memory rats were trained on a 12-arm radial maze with six arms baited and six arms unbaited until stable performance was achieved. Administration of 2.0 mg/kg d-amphetamine sulfate increased both working and reference memory errors, but only if a 5-min delay was imposed after three successful choices. With no delay this dose had no reliable effect on either working or reference memory. Lower doses (0.5 or 1.0 mg/kg) were ineffective even when a delay was imposed during the test. We suggest that amphetamine heightens arousal, which disrupts accurate retention when the rat's attention to the relevant cues is interrupted, as during a brief delay. Alternative explanations are discussed.     

Chunking by Proximal Arm Cues Facilitates Rats′ Performance in the Radial Maze

Three experiments showed that training rats to chunk a 16-arm radial maze into striped and wire mesh (gridded) arms facilitates their spatial working memory for arm locations. Rats were trained to visit eight unblocked baited arms of a 16-arm radial maze (half-maze run) and then were exposed to the complete maze to sample the remaining eight baited arms (whole-maze run). The initially exposed eight arms were either all striped or all gridded on alternating trials for half the rats (Arm Cue Relevant, ACR group). The remaining rats (Arm Cue Irrelevant, ACI group) received a mixture of striped and gridded arms on their half-maze runs. Following this phase of segmented trials, all rats were exposed only to all 16 arms over a series of trials in the first two experiments. In the third experiment, the initial eight arms were either all striped or all gridded on alternating trials for all rats. During some second, whole-maze runs, however, all arms contained the same proximal cue. ACR rats made fewer reentries than ACI rats in all phases of all experiments. This difference was maintained over increasing delays between half- and whole-maze runs in the first experiment, changes in arm cue and blocking configurations in the second experiment, and removal of differential arm cues in the third experiment.     

Lesions of the caudate nucleus selectively impair "reference memory" acquisition in the radial maze

Groups of Long-Evans rats with bilateral lesions of the caudate nucleus, sham lesions, or no lesions were given one trial per day in an eight-arm radial maze. The same four maze arms were baited on each trial. The remaining four arms never contained food. Optimal performance required animals to enter each of the baited arms only once on each trial and to avoid entering the arms in the unbaited set. Rats with caudate lesions learned to enter each of the baited arms only once on each trial. However, these rats were severely impaired in learning to avoid entering the arms in the unbaited set. Implications for dual-memory theories are discussed.     

Rats form cognitive maps from spatial configurations of proximal arm cues in an enclosed 4-arm radial maze

Rats were trained to select a final, remaining baited arm following a 6- to 10-min delay following their entries into three experimenter-selected baited arms in an enclosed 4-arm radial maze containing different proximally cued arms. Rats’ accuracy in selecting the remaining baited arm was disrupted when the spatial configuration of arm cues was randomly varied over trials following initial training with one configuration in Experiment 1. In Experiment 2, the same rats acquired this task with the original and a new configuration of the same arm cues when each consistently occurred at a specific time of day (one in the morning, the other in the afternoon). Randomly varying the temporal presentations of these configurations following acquisition disrupted rats’ choice accuracy more within the new than the original configuration. Other rats in Experiment 3 learned this task with two configurations containing different types of arm cues (full arm inserts, objects at the arm entrances). When required to relearn this task with recombined configurations of pairs of arm cues from of each configuration, only rats presented pairs of arms arranged differently from that in their original configurations were unable to reacquire the task. Together these results support a cognitive map hypothesis more than a proximal arm cue list hypothesis. These findings were discussed in terms of recent versions of cognitive map theory (Benhamou, 1998; Poucet, 1993) and the possible limits of such processing (Roberts, 2001).     

Lesions of the dorsal subiculum and the dorsal hippocampus impaired pattern separation in a task using distinct and overlapping visual stimuli

The contribution of the dorsal subiculum (DS) and of the dorsal hippocampus (DH) to memory for distinct and overlapping visual stimuli was examined. Rats with selective lesions of the DS or the DH were compared to sham-operated rats on a delayed matching-to-place task guided by distal visual cues in a modified radial-arm maze. Overlapping distal visual cues could be perceived from three arm entrances (adjacent arms) and a unique set of distal cues were more likely to be seen from the other two arm entrances (distinct arms). Rats with DS lesions were impaired on trials with baited adjacent arms, but not on trials with baited distinct arms. Rats with DH lesions were impaired on both types of trials. These results suggest that the DS and the DH are necessary for pattern separation and that they may have different contributions to memory.     

Use of win-stay and win-shift strategies in place and cue tasks by medial caudate putamen (MCPu) lesioned rats

This study investigated the behavioral function of the medial caudate putamen (MCPu) in the solving of maze tasks. MCPu lesioned rats (n = 35) and control rats (n = 35) were trained for the place or cue task (the four baited arms and four unbaited arms task) in an eight-arm radial maze, which requires the win-stay or the win-shift strategy. In Experiment 1, in which the place task was used, MCPu lesioned rats could learn the task in the win-shift condition, but not in the win-stay condition. MCPu lesioned rats made a lot of unbaited errors in the win-stay condition, as they persistently chose adjacent arms. Control rats could learn the tasks in both conditions. In Experiment 2, in which the cue task was used, MCPu lesioned rats and control rats could learn the tasks in both the win-stay and the win-shift conditions. If anything, the performance of MCPu rats was a little better than that of control rats in the win-stay condition. The results of these two experiments revealed that the MCPu was involved in solving the win-stay place task, but not the win-shift place, win-stay cue, and win-shift cue tasks. These findings suggest that the MCPu plays an important role in utilizing both spatial information and switching foraging strategies flexibly and efficiently, that is, processing complicated visuospatial cognition.     

Wistar rats with high versus low rearing activity differ in radial maze performance

Substantial work has shown that rats although identical in stock, sex, age, and housing conditions can differ considerably in terms of behavior and physiology. Such individual differences, which can be detected by specific behavioral screening tests, are rather stable, that is, they probably reflect a behavioral disposition or trait. Here, we asked whether and how such differences might affect performance in a task of spatial learning and memory, the radial maze. As in our previous work, we used the degree of rearing activity in a novel open field to assign male adult outbred Wistar rats into those with high versus low rearing activity (HRA/LRA rats). They were then tested in a plus-maze for possible differences in anxiety-related behavior. Finally, and most importantly, they were food deprived and underwent maze training using an 8-arm radial maze with four non-baited and four baited arms. One of these arms consistently contained a larger bait size than the other three. In the open field, HRA rats not only showed more rearing behavior, but also more locomotor activity than LRA rats. In the plus-maze, HRA rats again showed more locomotion, but did not differ in open arm time or percentage of open arm entries, that is, conventional measures of anxiety-related behavior. In the radial maze, HRA rats consistently needed less time to consume all pellets than LRA rats, which was due to faster locomotion on the arms and less time spent at the food pits (especially in baited arms) of HRA rats. During the initial days of training, they were also more efficient in obtaining all food pellets available. Furthermore, HRA rats visited more arms and made relatively less reference memory errors than LRA rats. This allowed them to forage food quickly, but was paralleled by more working memory errors than in LRA rats. In general, working memory errors were more frequent in the arm with the large bait size, but there were no indications that HRA and LRA rats responded differently dependent on reward size. Finally, LRA rats lost slightly more weight than HRA rats during the period of food deprivation. These results are discussed with respect to the role of cognitive and motivational mechanisms, which as subject-inherent factors can contribute substantially to inter-individual variability in the radial maze.     

Preoperative enrichment and behavioral recovery in rats with septal lesions

To assess the behavioral effects of preoperative differential housing male rats were placed in either enriched or isolated environments at weaning prior to receiving either sham operations or septal lesions when 57 days of age. Rats with septal lesions showed reduced habituation of ambulation and initially made fewer rears in an empty open field but made more object-contacts coupled with a lack of habituation in the object-filled field. Septal rats also showed severe impairments when tested in a 12-arm radial maze with 7 arms baited and 5 arms unbaited. Preoperative enrichment did not significantly affect these lesion-induced changes. Nevertheless, enrichment significantly lowered ambulation (but did not affect habituation) in the open field and increased the number of manipulatory relative to nonmanipulatory contacts. However, preoperatively enriched septal rats showed a deficit in spontaneous alternation (45%) in contrast to the high levels (83%) shown by intact enriched rats, whereas both intact and septal isolated rats showed similar levels of spontaneous alternation (68%). These results conflict with earlier reports that preoperative enrichment "protects" rats against the deficits produced by septal lesions.     

Algorithmic responding on the radial maze in rats does not always imply absence of spatial encoding

Two experiments were conducted to determine whether consistent algorithmic response patterning on 8- and 10-arm versions of the radial maze is independent of spatial encoding. On the 8-arm version well-trained hooded rats were tested in darkness, after maze rotation that rendered room cues ambiguous with respect to arm positions, or with room cues unsystematically relocated. Ambiguous maze rotation was also used with well-trained subjects on the 10-arm version. If algorithmic patterning is a learned, non-spatial strategy, animals using it consistently ought not to have been affected by changes in the spatial layout of the test environment, and the type of pattern used by each subject would have remained constant. On the 8-arm radial maze, responses were most often made to arms 2 or 3 from that just visited. In many animals patterns were interchangeable, switching occurring between preferred angles of turn from day to day. Performance fell when animals were tested in darkness and upon ambiguous maze rotation early (but not later) in training. Testing in darkness increased the angle through which animals turned when responding, perhaps due to the disturbance of intramaze cue use. On the 10-arm maze the “consecutive arm” pattern was used persistently by several animals and appeared to protect their performance from disruption by ambiguous maze rotation. Animals not using rigid patterning were adversely affected. However, on both mazes animals using patterning correctly identified maze arms that had been omitted from otherwise patterned choice sequences. Animals adopted continuous patterning only when spatial encoding had been established. Response patterning appears to serve a mnemonic function and in rats complements rather than replaces the use of a spatial representation of the environment. It was concluded that a complex, flexible relationship exists between spatial functioning and its expression via motor responses.     

Does a cognitive map guide choices in the radial-arm maze?

Fifteen rats performed in a standard radial-arm maze task (Experiment 1) and in a modified task with a set of forced choices and a 15-min retention interval prior to completion of the maze (Experiment 2). In addition to the standard measure of choice in the radial-arm maze, orientation toward arms was measured and considered to constitute go-no-go "microchoice" decisions. Rats investigated but rejected many arms. A model of choice was developed in which it was assumed that choice decisions about arms were made independently and that microchoices were not selectively guided toward baited arms. The model performed nearly as well as the rats. These results place important limitations on the theory that choice behavior in the radial-arm maze is guided by a cognitive map.     

How rats perform spatial working memory tasks: Limitations in the use of egocentric and idiothetic working memory

Rats of the Dark Agouti strain were trained on delayed alternation under conditions that should encourage egocentric working memory. In two experiments a T-maze was set within a cross-maze so that different arms could be used for the sample and test runs. The maze had high opaque side-walls, and testing was conducted in low light levels so that distal visual cues might be eliminated. By rotating the maze 90° between the sample and choice run and by using two identical mazes set side by side it was possible to nullify other spatial strategies. Experiments 1 and 2 showed that rats preferentially used place information, intramaze cues, and direction cues, even though only egocentric or idiothetic (nonmatch-to-turn) working memory could successfully solve every trial. Rats were able to maintain an accurate sense of location within the maze even though distal cues were not visible and the animal was moved between the sample and choice runs. Experiment 2 confirmed that another rat strain (Long-Evans) shows the same learning profiles. Both experiments indicate that rats are very poor at using either egocentric or idiothetic information to alternate, and that retention delays as short as 10 s can eliminate the use of these forms of memory.     

Spatial memory in rats: A cross validation study

Two experiments were performed to investigate whether two measures of spatial memory, working memory (WM) and reference memory (RM), can be generalized over learning situations. In the first experiment, outbred WU rats were used; in the second four inbred strains. In both experiments rats were given 50 training trials in both a holeboard and a high-sided radial maze: 4 out of 16 holes and 4 out of 8 arms were baited. The number of WM (revisits to baited holes/arms) and RM (visits and revisits to never baited holes/arms) errors were calculated for 5 blocks of 10 trials; odd-even reliabilities were determined for the last 20 trials and were shown to be satisfactory for both measures in both types of apparatus. Error-decrements were analyzed by trend components. For both WM and RM, simple and canonical correlations were determined between means and significant trends in maze and holeboard as a test for construct validity; in both experiments r's and R_c's were very low. It was concluded that the concepts WM and RM are not validly generalizable over tests.     

How rats perform spatial working memory tasks: limitations in the use of egocentric and idiothetic working memory

Rats of the Dark Agouti strain were trained on delayed alternation under conditions that should encourage egocentric working memory. In two experiments a T-maze was set within a cross-maze so that different arms could be used for the sample and test runs. The maze had high opaque side-walls, and testing was conducted in low light levels so that distal visual cues might be eliminated. By rotating the maze 90° between the sample and choice run and by using two identical mazes set side by side it was possible to nullify other spatial strategies. Experiments 1 and 2 showed that rats preferentially used place information, intramaze cues, and direction cues, even though only egocentric or idiothetic (nonmatch-to-turn) working memory could successfully solve every trial. Rats were able to maintain an accurate sense of location within the maze even though distal cues were not visible and the animal was moved between the sample and choice runs. Experiment 2 confirmed that another rat strain (Long-Evans) shows the same learning profiles. Both experiments indicate that rats are very poor at using either egocentric or idiothetic information to alternate, and that retention delays as short as 10 s can eliminate the use of these forms of memory.     

Spatial memory for food hidden by rats (Rattus norvegicus) on the radial maze: studies of memory for where,what, and when

Rats (Rattus norvegicus) were allowed to hide food items on an 8-arm radial maze by carrying the items from the center to boxes at the end of each arm. Retrieval tests given after rats had hidden 4 items showed that they selectively returned to the maze arms where food had been hidden (Experiments 1 and 2). When rats were allowed to hide pieces of cheese (refed food) and pretzels (less preferred food) on different arms, they both hid and retrieved cheese before pretzels (Experiments 2-5). In Experiment 6, rats chose between arms where cheese and pretzels were hidden,with cheese degraded at one delay interval but not the other. Together, these experiments indicate memory for what and where but not when.     

Memory systems in the rat: effects of reward probability,context, and congruency between working and reference memory

The interaction of working and reference memory was studied in rats on an eight-arm radial maze. In two experiments, rats were trained to perform working memory and reference memory tasks. On working memory trials, they were allowed to enter four randomly chosen arms for reward in a study phase and then had to choose the unentered arms for reward in a test phase. On reference memory trials, they had to learn to visit the same four arms on the maze on every trial for reward. Retention was tested on working memory trials in which the interval between the study and test phase was 15 s, 15 min, or 30 min. At each retention interval, tests were performed in which the correct WM arms were either congruent or incongruent with the correct RM arms. Both experiments showed that congruency interacted with retention interval, yielding more forgetting at 30 min on incongruent trials than on congruent trials. The effect of reference memory strength on the congruency effect was examined in Experiment 1, and the effect of associating different contexts with working and reference memory on the congruency effect was studied in Experiment 2.     

Vasopressin disrupts radial-maze performance in rats

The memory enhancing properties of vasopressin, observed in active and passive avoidance procedures, could derive from its influence on central systems, but may also be mediated by its endocrinological properties. Very little is known about the effects of vasopressin on behavior in procedures other than the active and passive avoidance paradigms. The present experiments were designed to assess the effects of vasopressin on behavior observed in the eight-arm radial maze. In Experiment I, male Wistar rats (N = 7), which had been extensively trained to collect food from all eight arms in a radial maze, were subcutaneously injected with different doses of vasopressin 5 min before the start of the session (0.00, 1.25, 3.75, and 6.25 micrograms/kg). In Experiment II, another group of male Wistar rats (N = 7) received the same doses of vasopressin after having been extensively trained to collect food from four of the eight arms. In both experiments, subjects spent more time in the maze as the dose of vasopressin was increased. Vasopressin also disrupted performance by preventing the subjects from visiting all of the baited arms in the maze. Performance thus decreased, not because of the fact that vasopressin interfered with memory processes, but because of the fact that it produced behavioral inhibition. Thus, if vasopressin affects memory processes, such effects are likely to be mediated through vasopressin's actions on endocrine and behavioral systems, rather than through a direct action on the neural substrate underlying memory functioning.     

A comparison of the effects of fimbria-fornix, hippocampal, or entorhinal cortex lesions on spatial reference and working memory in rats: short versus long postsurgical recovery period.

Using a radial maze task and different postoperative recovery periods, this experiment assessed and compared the reference and working memory performances of adult Long-Evans male rats subjected to entorhinal cortex, fimbria-fornix, and hippocampus lesions. Sham-operated rats were used as controls. In order to see whether the duration of the postsurgical recovery period would influence acquisition of the complex radial maze task, training began 1 month following surgery (Delay 1) for half the rats in each group, while for the other half training was started 6.5 months following surgery (Delay 2). The results indicated that at both recovery periods the entorhinal cortex lesions failed to affect either working or reference memory in the spatial task. Conversely, both fimbria-fornix and hippocampus lesions impaired both reference and working memory. While the reference memory deficit was generally similar in both fimbria-fornix and hippocampal lesion groups, analysis of the results for working memory indicated that at the longer delay rats with fimbria-fornix lesions were still impaired but in animals that had the hippocampus removed, working memory did not differ from that of controls. These results suggest that there was some recovery in those rats with hippocampal lesions (e.g., on the working memory task) but both hippocampal and fimbria-fornix animals were still impaired compared to controls when training was delayed 6.5 months following the operations.     

Gerbils in space: performance on the 17-arm radial maze.

In Experiment 1 six hungry gerbils received six trials per day on a 17-arm radial maze. During each trial the subjects were allowed to choose freely among the arms, each of which contained a food pellet, until each arm had been visited once or until eight minutes had elapsed. An error was recorded when the subject entered a previously visited arm. The gerbils quickly learned not to re-enter previously visited arms and generally made errors on fewer than 15% of entries, performance comparable to that of the rat and superior to that of other species tested in the radial arm maze. The intertrial-interval duration did not affect accuracy of arm choices during acquisition but did influence asymptotic accuracy. Accuracy did not change systematically over the six trials. A high proportion of arm entries were to nearby arms. Errors occurred most often towards the end of a trial. Odor cues were not important. When the number of trials per day was reduced from six to one, accuracy deteriorated slightly. In Experiment 2 neither the transposition of extramaze cues nor the placement of the maze in a different room had large disruptive effects on accuracy. In Experiment 3 the addition of three explicit intramaze brightness cues aided accuracy, perhaps by permitting the subjects to decompose the large maze into three smaller mazes, although there was no direct evidence that this was the case. Implications of a number of these results for models of spatial maze performance were discussed.     

Chronic administration of corticosterone impairs spatial reference memory before spatial working memory in rats

Corticosterone (CORT), the predominant glucocorticoid in rodents, elevated for 21 days damages hippocampal subregion CA3. We tested the hypothesis that CORT would impair spatial memory, a hippocampal function. In each of the three experiments, rats received daily, subcutaneous injections of either CORT (26.8 mg/kg body weight in sesame oil) or sesame oil vehicle alone (VEH). CORT given for 21 or 56 days effectively attenuated body weight gain and reduced selective organ and muscle weights. All behavioral testing was done on tasks that are minimally stressful and avoid deprivation. For each experiment, testing commenced 24h after the last injection. CORT given for 21 days did not impair spatial working memory in the Y-maze (Experiments 1 and 2). After 56-day administration of CORT, spatial working memory was impaired in the Y-maze (Experiment 2). CORT given for 21 days also failed to impair spatial working memory in the Barnes maze (Experiment 3). However, in trials that depended solely on reference memory, the VEH group improved in performance, whereas the CORT group did not. In conclusion, CORT elevated over a period of 21 days did not impair spatial working memory, but impaired the formation of a longer-term form of memory, most likely reference memory. Impairments in spatial working memory are seen only after longer durations of CORT administration.     

High-fat diets impair spatial learning in the radial-arm maze in mice

It has been suggested that hyperglycemia and insulin resistance triggered by energy-dense diets can account for hippocampal damage and deficits of cognitive behaviour. We wonder if the impairment of learning and memory processes detected in diet-induced obese (DIO) mice is linked to diet composition itself. With this purpose we have evaluated learning performance in mice undergoing a short-term high-fat (HF) treatment, which leads to a pre-obese state characterized by increased adiposity without significant changes of glucose and insulin plasma levels. C57BL/6J mice were fed either a HF (45 kcal% from fat) or control diet (10 kcal% from fat) during 8 weeks. Learning performance was evaluated by using the four-arm baited version of the eight-arm radial maze test (RAM). Mice were trained to learn the RAM protocol and then memory was tested at different time-points. Time spent to consume food placed in baited arms and errors committed to find them were measured in all sessions. DIO mice significantly spent more time in learning the task and made a greater number of errors than controls. Moreover, retention tests revealed that both working and total memory errors were also more numerous in DIO mice. The current results show that short-term DIO impairs spatial learning and suggest that impairment of hippocampal learning elicited by HF diets might be perceptible before metabolic alterations linked to obesity develop.