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.     

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.     

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.     

Domestic dogs (Canis familiaris) and the radial arm maze: Spatial memory and serial position effects

The present study investigated spatial memory in domestic dogs (Canis familiaris) through the use of a radial arm maze. The study consisted of a total of three separate experiments. In the first two experiments, the ability of the dogs to successfully remember previously unentered arms was evaluated. The third experiment was similar to the first two, but also examined the nature of the serial position effect. Performance in all three experiments was better than expected solely by random choices. Dogs showed a much better memory for spatial locations presented earlier in a spatial list compared with those presented in the middle. Based on the present results, we suggest that the radial arm maze assesses canine spatial memory and that dogs show a primacy effect. (PsycINFO Database Record (c) 2012 APA, all rights reserved).     

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.     

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.     

Spatial navigation in complex and radial mazes in APP23 animals and neurotrophin signaling as a biological marker of early impairment

Impairment of hippocampal function precedes frontal and parietal cortex impairment in human Alzheimer's disease (AD). Neurotrophins are critical for behavioral performance and neuronal survival in AD. We used complex and radial mazes to assess spatial orientation and learning in wild-type and B6-Tg(ThylAPP)23Sdz (APP23) animals, a transgenic mouse model of AD. We also assessed brain content of nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and neurotrophin-3 (NT-3). Performance was alike in wild-type and APP23 animals in the radial maze. In contrast, performance in the complex maze was better in wild-type than APP23 animals. Contrary to the wild-type, hippocampal BDNF levels decreased on training in APP23 animals. Hippocampal and frontal cortex NGF levels in APP23 animals correlated with the time to solve the complex maze, but correlated inversely with escape time in wild-type animals. NT-3 levels were alike in wild-type and APP23 animals and were unchanged even after training. Both types of mazes depend on hippocampal integrity to some extent. However, according to the cognitive mapping theory of spatial learning, the complex maze because of the increased complexity of the environment most likely depends more strongly on preserved hippocampal function than the radial maze in the working memory configuration applied here. Greater impairment in complex maze performance than in radial maze performance thus resembles the predominant affliction of the loss of hippocampal function in human AD. NGF and BDNF levels on maze learning are different in wild-type and transgenic animals, indicating that biological markers of AD may be altered on challenge even though equilibrium levels are alike.     

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.     

The role of response and reward in spatial memory

Two experiments were conducted to determine the role of the response and of reward in spatial working memory. Rats were initially trained on a four-arm maze to run to the end of each arm for a single pellet of food. On subsequent tests, rats were first placed at the end of one, two, or three arms. In Experiment 1, the arms on which the rat was placed (“placed arms”) had food which the rat was allowed to eat, whereas in Experiment 2 these placed arms did not have food. Following the placements the rat was allowed to choose among the four arms; only unplaced arms contained food. Two measures indicated that the response made a slight but reliable contribution to spatial memory. (a) When a rewarded arm was still available, choice accuracy after placements was less than choice accuracy on tests in which no placements had occurred; this difference diminished over test days. (b) When all four arms had been chosen once, the rats were more likely to go back to a placed arm rather than an unplaced arm. No influence of the presence or absence of food on the placed arms was found. These data demonstrate that the response of running down an arm, but not the reward outcome at the end, had a small influence on the memorability of a visit. Overall, above chance performance in the spatial working memory task was maintained without either running to the arm or obtaining food on it.     

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     

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.     

Radial arm maze performance of mice: acquisition and atropine effects

CD-1 mice were successfully trained in a six-arm radial maze in which half of the arms were baited, a procedure which had been used to differentiate between reference and working memory. Stable performance was achieved following eight daily training sessions, as measured by decreasing running time and number of errors. This finding strengthens the foraging hypothesis as a basis for the performance of rodents in the radial maze. Acute subcutaneous administration of the cholinergic antagonist atropine sulfate (1-6 mg/kg) to trained mice produced dose-related increases in running time and working memory errors, with a slight decrease in reference memory errors. This is in agreement with other studies on the role of the cholinergic system in memory processes. The peripheral cholinergic blocker, atropine methyl nitrate (4 mg/kg), somewhat increased running time without decreasing performance accuracy. In contrast to the prolonged pharmacological and physiological effects of atropine, behavioral decrements disappeared within 3 hr. It is concluded that mice trained in the radial arm maze may be used for screening of the effects of drugs on cognitive function.     

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.     

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.     

How does the ecological foraging behavior of desert kangaroo rats (Dipodomys deserti) relate to their behavior on radial mazes?

Experiment 1 showed that laboratory-reared desert kangaroo rats, like domestic Norway rats, efficiently search for food on a radial arm maze (RAM) by avoiding revisiting arms within a trial. By placing an RAM on the floor so the animals could approach food from any direction, Experiment 2 tested whether efficient search by kangaroo rats was based on tactics of distance minimizing, central-place foraging, trail following, or meandering. In contrast to the dominant trail-following tactic of domestic Norway rats (Hoffman, Timberlake, Leffel, & Gont, 1999), kangaroo rats tended to distance minimize, whether maze arms were present or not. Experiment 3 indicated that kangaroo rats treated a floor configuration of eight food cups as two patches of four, based on beeline travel between patches and meandering within them. We conclude that similar performance in an elevated RAM by different species can be based on different tactics, and we suggest that a laboratory apparatus can be used to cast light on niche-related mechanisms.     

Chunking versus foraging search patterns by rats in the hierarchically baited radial maze

Rats were exposed to a radial maze containing six black smooth arms and six wire-grid-covered arms and a striped 'exit arm' in experiment 1. The probability of a black or grid arm being baited (5/6 vs 1/6) with sunflower seeds was associated with its proximal cue for some rats (the Relevant Arm Cue group) but not for others (the Irrelevant Arm Cue group). All rats could terminate a trial and receive a highly preferred morsel of apple by entering the exit arm only after having sampled all six seed-baited arms. Relevant Arm Cue rats usually chose some arms from the more densely baited set before choosing an arm from the less densely baited set and made fewer reentries than Irrelevant Arm Cue rats. Although such clustered, higher choice accuracy in the Relevant Arm Cue group corresponds to human clustered, better recall of verbal items from lists hierarchically organized by categories, these rats did not similarly exhaustively retrieve items (arm locations). That is, when required to terminate a trial by entering the 'exit' arm for an apple morsel after having sampled all seed-baited arms, both groups were equally unable to withhold making nonrewarded premature exits. This nonexhaustive foraging search pattern was maintained in the next two experiments in which the radial maze was reduced to three black and three grid arms along with the striped 'exit' arm and in which black and grid arm cues were paired with number of seeds (eight or one) in an arm for Relevant Arm Cue rats. Although Relevant Arm Cue rats displayed perfect clustering by entering all eight-seeded arms before a one-seeded arm, they made more premature exits and reentries into eight-seeded arms in experiment 2 or when forced to enter all eight-seeded arms in experiment 3 than did Irrelevant Arm Cue rats. These foraging tendencies prevent accurate estimations of the amount of information (i.e., arm locations) rats can 'chunk'. Electronic Publication     

Working memory deficits in transgenic rats overexpressing human adenosine A2A receptors in the brain

Adenosine receptors in the central nervous system have been implicated in the modulation of different behavioural patterns and cognitive functions although the specific role of A(2A) receptor (A(2A)R) subtype in learning and memory is still unclear. In the present work we establish a novel transgenic rat strain, TGR(NSEhA2A), overexpressing adenosine A(2A)Rs mainly in the cerebral cortex, the hippocampal formation, and the cerebellum. Thereafter, we explore the relevance of this A(2A)Rs overexpression for learning and memory function. Animals were behaviourally assessed in several learning and memory tasks (6-arms radial tunnel maze, T-maze, object recognition, and several Morris water maze paradigms) and other tests for spontaneous motor activity (open field, hexagonal tunnel maze) and anxiety (plus maze) as modification of these behaviours may interfere with the assessment of cognitive function. Neither motor performance and emotional/anxious-like behaviours were altered by overexpression of A(2A)Rs. TGR(NSEhA2A) showed normal hippocampal-dependent learning of spatial reference memory. However, they presented working memory deficits as detected by performance of constant errors in the blind arms of the 6 arm radial tunnel maze, reduced recognition of a novel object and a lack of learning improvement over four trials on the same day which was not observed over consecutive days in a repeated acquisition paradigm in the Morris water maze. Given the interdependence between adenosinic and dopaminergic function, the present results render the novel TGR(NSEhA2A) as a putative animal model for the working memory deficits and cognitive disruptions related to overstimulation of cortical A(2A)Rs or to dopaminergic prefrontal dysfunction as seen in schizophrenic or Parkinson's disease patients.     

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.