Working memory theory of hippocampal function needs qualification

To compare the predictive value of "cognitive map" and "working memory" theories of hippocampal function, the performance of rats with dorsal hippocampal lesions was compared to that of control rats in a series of experiments. In Experiment I, experimental rats learned a spatial alternation task with normal ease, but in Experiment II, they were significantly impaired on an elevated 8-arm radial maze. In Experiment III, the performance of the same experimental and control rats was compared on two versions of a 16-arm enclosed radial maze. In the first version, carpet inserts served as cues to mark eight unbaited arms and each of the remaining arms contained one food pellet. While both experimental and control rats successfully avoided the set of cued arms, experimental rats reentered uncued baited arms more frequently than did control rats. In the second version no intramaze cues were provided, but the spatial distribution of baited and unbaited arms remained the same as that used in the first version. In this uncued version, experimental rats both entered unbaited arms and reentered baited arms more frequently than did control rats, i.e., they were impaired in both "reference" and "working" memory. These findings are compatible with the hypothesis that hippocampal lesions result in an impaired capacity to form cognitive maps but they are not compatible with the working memory hypothesis. Furthermore, twelve separate evaluators classed experimental rats as using fewer mapping and more orientation strategies than control rats in the 8-arm maze.     

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.     

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.     

Caudate nucleus and memory for egocentric localization

A large body of evidence suggests that the caudate nucleus (CN) plays a critical role in the processing of spatial localization information. Furthermore, evidence has begun to accumulate that the CN is involved in the processing of a very specific class of spatial cues, namely, egocentric cues (localization with reference to the organism). This is in contrast to allocentric localization, where an organism localizes on the basis of cues external to the organism. One would then predict that lesions to the CN should disrupt performance on any tasks that depend chiefly on egocentric spatial cues, while leaving performance on allocentric tasks intact. To test this prediction, two groups of rats were trained on two different egocentric memory tasks and two different allocentric memory tasks. Specifically, one group of rats was trained on an adjacent-arm (egocentric) and an 8-arm radial maze task (allocentric). A second group of rats was trained on a right-left discrimination (egocentric) and a place-learning task (allocentric). After training, both groups received bilateral lesions of the CN. Results showed that CN-lesioned animals were profoundly impaired on retention of the egocentric tasks. In sharp contrast to this, the same animals were not or were only transiently impaired or transiently affected on allocentric tasks. Sham-operated controls were either unimpaired or transiently affected on all tasks. These findings further support the idea that the CN plays a critical modulatory role in the processing of egocentric spatial and not allocentric spatial cues.     

Rats use a sense of direction to alternate on T-mazes located in adjacent rooms

Lister hooded rats were trained on a forced-sample T-maze alternation task in an environment lacking spatial landmarks. An early study of spontaneous alternation on the T-maze had shown that rats use a "spatial sense" to select alternate maze arms across mazes. As this phenomenon may provide a useful tool for studying the neural substrates of a directional sense, we wished to confirm this finding on a different version of the T-maze task, with well-trained animals. We found that rats successfully selected the appropriate maze arm when the choice phase of the task was presented on a second maze, oriented in the same direction, and located in an adjacent room. However, choice performance fell to chance level when the second maze was oriented 90° relative to the first. This result suggests that the rats do not simply alternate turns across the two environments, but rather that they rely on a sense of direction that is carried across environments. Electronic Publication     

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).     

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.     

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.     

Strategy selection in a task with spatial and nonspatial components: effects of fimbria-fornix lesions in rats.

The main purpose of the present research was to investigate the ability of rats to learn a 12-arm radial maze task that requires the concurrent utilization of both spatial and intramaze cue information. The task involves in a single trial both place and cue learning as well as reference memory (RM) and working memory (WM). Since the animal can choose place and cue arms in any order, the strategies employed to learn the task can be studied as well as the kinds of memory errors that are made. The results of Experiment 1 showed that the number of errors made on the place and cue components of the task did not differ, and that more RM than WM errors were made early during learning. As the task was learned, the animals tended to choose the place arms before choosing the intramaze cue arms, thus suggesting that a spatial strategy was employed first followed by a cue strategy. In Experiment 2 lesions of the fimbria-fornix resulted in temporary impairments in both RM and WM that were especially apparent on the spatial component of the task. The lesioned rats also switched from choosing mostly place arms early during the trial to choosing more cue arms. While fimbria-fornix lesioned rats recovered from the memory impairments with training, the change in response strategy persisted throughout postoperative testing. The procedure of combining both spatial and non-spatial components concurrently in the same task should prove of value in studying response strategies in animals.     

Pre-training to find a hidden platform in the Morris water maze can compensate for a deficit to find a cued platform in a rat model of Parkinson's disease

The bilateral intranigral infusion of 1 micromol 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in adult male Wistar rats caused a specific and partial loss of substantia nigra pars compacta (SNc) dopamine neurons, a partial depletion of striatal dopamine, and a deficit to learn the intra-maze cued version of the Morris water maze. Pre-training the SNc rats in the spatial version of the water maze or simply maintaining the animals on the water maze platform reversed this deficit. This improvement was even observed when the order of the extra-maze cues presented to the rats during pre-training of the spatial version was changed during training of the intra-maze cued version. However, this deficit was not reversed either by maintaining the animals on the platform if the spatial cues were surrounded and covered with a curtain or by swimming sessions in the maze without the escape platform and the curtain. These findings suggest that none of the following elements alone, learned during the spatial task pre-training, could help SNc rats learn the intra-maze cued task: improvement of swimming skills or knowledge of the existence of the escape platform; distance between the platform and the border of the pool; location of a particular extra-maze cue; relations among extra-maze cues. However, the simultaneous presence of the escape platform and extra-maze cues (irrespective of their relational configuration) during the pre-training sessions proved to be necessary for this improving effect to occur.     

Central-place foraging by Rattus norvegicus on a radial maze

We studied central-place foraging in rats (Rattus norvegicus) by placing food items that varied in size and weight at the ends of a 4-arm radial maze. In Experiments 1-3, rats increasingly tended to carry food to the center of the maze as the size of those items increased. Very large food items often were hoarded in the center. Rats consumed food faster on the arms than in the center, and rats traveled faster when carrying food than when not. Blocking arm entrances increased travel time between the center and the arms and decreased food carrying at every item weight except the largest. In Experiments 4-6, important conditions that influence the degree of food-carrying behavior were discovered; these were the intersection of maze arms, the presence of a conspecific, and the use of open vs. closed maze arms.     

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.     

Spatial learning and memory in the tortoise (Geochelone carbonaria)

A single tortoise (Geochelone carbonaria) was trained in an eight-arm radial maze, with the apparatus and general procedures modeled on those used to demonstrate spatial learning in rats. The tortoise learned to perform reliably above chance, preferentially choosing baited arms, rather than returning to arms previously visited on a trial. Test sessions that examined control by olfactory cues revealed that they did not affect performance. No systematic, stereotyped response patterns were evident. In spite of differences in brain structure, the tortoise showed spatial learning abilities comparable to those observed in mammals.     

Distinguishing between new and used traces: Differential effects of electroconvulsive shock on memories for places presented and places passed

In a radial maze test of spatial memory, rats enter relatively novel arms while avoiding locations visited a few hours earlier. Certainly, new memories are acquired for arms entered during the retention test. However, the mnemonic consequences of avoiding arms previously entered are not as clearly predicted; old memories might remain unchanged and yet guide behavior, or the use of old memories during a retention test might renew such memories. The possibilities were evaluated in two experiments in which rats performed in a 12-arm radial maze. Each day the arms were randomly sorted into three sets: A, B, C. Each trial began with forced choices of the 4 arms in Set A and ended after 4 hr in an 8-choice test in which the 4 arms not yet visited (Set B) contained food reward. When electroconvulsive shock (ECS) occurred immediately after Set A choices, accuracy during the test was high; when ECS was administered 2 hr after Set A, choices during the test were less accurate. Old memories therefore appear to be more susceptible than new memories to ECS-induced amnesia. In other trials, an extra retention test was given at the mid-point (2 hr) of the retention interval; this 8-choice test consisted of the remaining 4 arms (Set C) and the original 4 arms (Set A). When ECS was administered after the intermediate test, memory for arms in Set A was 2 hr old (but had just been used), while memory for arms in Set C was new (0 hr). The retention test 2 hr later (testing B vs. A or B vs. C) revealed that ECS had an amnestic effect on the recently used memory for arms in Set A but had no effect on the newly acquired memory for arms in Set C. With respect to ECS-induced amnesia, therefore, memories used in a retention test resemble memories that have aged more than memories that have been newly acquired.     

Effects of pre-exposure to the same or different pattern of extra-maze cues on subsequent extra-maze discrimination

In two experiments, rats learned a spatial discrimination between maze arms defined by their relationship to a variety of extra-maze cues. Prior exposure to the actual arms between which animals were required to discriminate tended to retard subsequent learning (by comparison with a control group either given no pre-exposure to the extra-maze cues or exposed only to arms pointing in the opposite direction), whereas prior exposure to arms intermediate between those used in discrimination training tended to facilitate subsequent learning. These results are consistent with the suggestion that pre-exposure will facilitate discrimination learning when it reduces the associability of features or elements common to the stimuli between which animals are required to discriminate, more than it reduces the associability of the features or elements unique to each.     

Spatial learning and memory is preserved in rats after early development in a microgravity environment

This study evaluated the cognitive mapping abilities of rats that spent part of their early development in a microgravity environment. Litters of male and female Sprague-Dawley rat pups were launched into space aboard the National Aeronautics and Space Administration space shuttle Columbia on postnatal day 8 or 14 and remained in space for 16 days. These animals were designated as FLT groups. Two age-matched control groups remained on Earth: those in standard vivarium housing (VIV) and those in housing identical to that aboard the shuttle (AGC). On return to Earth, animals were tested in three different tasks that measure spatial learning ability, the Morris water maze (MWM), and a modified version of the radial arm maze (RAM). Animals were also tested in an open field apparatus to measure general activity and exploratory activity. Performance and search strategies were evaluated in each of these tasks using an automated tracking system. Despite the dramatic differences in early experience, there were remarkably few differences between the FLT groups and their Earth-bound controls in these tasks. FLT animals learned the MWM and RAM as quickly as did controls. Evaluation of search patterns suggested subtle differences in patterns of exploration and in the strategies used to solve the tasks during the first few days of testing, but these differences normalized rapidly. Together, these data suggest that development in an environment without gravity has minimal long-term impact on spatial learning and memory abilities. Any differences due to development in microgravity are quickly reversed after return to earth normal gravity.     

Spatial memory in rats under restricted viewing conditions

In a procedure devised by J. A. Walker and D. S. Olton (Learning and Motivation, 1979, 10, 73–84), rats were placed on two arms of a four-arm radial maze and then were placed in the center of the maze to test how accurately they could choose the alleys on which they had not been placed. In three experiments, the conditions under which animals viewed the environment from the arms were varied. In Experiment 1, both the extent of spatial view and the exposure time were varied factorially in a within-subjects design; animals viewed the environment down a tunnel or had a 180° or 360° view, and subjects were allowed to view the environment for either 2 or 20 sec. In Experiment 2, a between-subjects design was used, in which different groups of subjects were tested repeatedly under either the tunnel, 180°, or 360° conditions. Both experiments showed that animals could avoid the arms previously visited at no better than a chance level of accuracy in the tunnel viewing condition but could perform with progressively better accuracy at the 180 and 360° viewing conditions. Animals also were more accurate in Experiment 1 after viewing for 20 sec than after viewing for 2 sec. Experiment 3 involved a procedure in which restricted viewing conditions were used both during arm placements and testing. Animals tested under tunnel viewing eventually achieved above-chance performance with this procedure, but did not exceed chance as rapidly as groups tested with 45 and 90° views of the environment. These results suggest that animals can learn about their position in a spatial environment through observation and that an animal's ability to locate its position is directly related to the extent of the surrounding environment it can see and the length of time it is allowed to look. The implications of these findings for list and map hypotheses of spatial memory representation are discussed.     

A test of the reward-value hypothesis

Rats retain source memory (memory for the origin of information) over a retention interval of at least 1 week, whereas their spatial working memory (radial maze locations) decays within approximately 1 day. We have argued that different forgetting functions dissociate memory systems. However, the two tasks, in our previous work, used different reward values. The source memory task used multiple pellets of a preferred food flavor (chocolate), whereas the spatial working memory task provided access to a single pellet of standard chow-flavored food at each location. Thus, according to the reward-value hypothesis, enhanced performance in the source memory task stems from enhanced encoding/memory of a preferred reward. We tested the reward-value hypothesis by using a standard 8-arm radial maze task to compare spatial working memory accuracy of rats rewarded with either multiple chocolate or chow pellets at each location using a between-subjects design. The reward-value hypothesis predicts superior accuracy for high-valued rewards. We documented equivalent spatial memory accuracy for high- and low-value rewards. Importantly, a 24-h retention interval produced equivalent spatial working memory accuracy for both flavors. These data are inconsistent with the reward-value hypothesis and suggest that reward value does not explain our earlier findings that source memory survives unusually long retention intervals.     

Spatial memory over long retention intervals: nonmemorial factors are not necessary for accurate performance on the radial-arm maze by rats

A. Markowska, O. Buresová, and J. Bures (1983, Behavioral and Neural Biology, 38, 97-112) argued that the apparent persistence of accurate spatial working memory over delays of several hours arises from the formation of response strategies and the use of olfactory stimuli that develop with extended training at long delays. To test this explanation rats with extensive prior training at long delays were forced to enter the first four arms in a random order. On test days, the maze was rotated 180 degrees during the 2-h retention interval to determine whether the rats were using intramaze or extramaze (i.e., spatial) cues to guide their choices. On both rotation and control days, postdelay choices were spatially guided, averaging over 90% correct. Accurate spatial working memory at long delays is a reproducible phenomenon and does not appear to result from nonmemorial artifacts.     

Hierarchical structures: chunking by food type facilitates spatial memory

Three experiments assessed the ability of male Sprague-Dawley rats to organize the spatial locations of different food types in a hierarchical manner to maximize the efficiency of working memory. Independent groups were exposed, on a 12-arm radial maze, to baiting arrangements varying in the stability of the pattern and type of food used as bait. Training rats with stable, differentiable baiting arrangements produced increased accuracy in choice performance, hierarchically ordered patterns of choice selection, slower growth of proactive interference when trials were massed, and the learning of the geometrical relations among food types independent of other extramaze cues. Such findings are strong evidence of the rat's ability to encode and use local cues for navigation, based on properties of the reinforcer. The application of a chunking strategy may provide for more efficient use of working memory by facilitating information storage, recall, or resetting mechanisms.