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.     

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.     

Spontaneous alternation and pattern of reinforcement

In Experiment I, rats were given one pair of trials per day in a T-maze; group RN were rewarded on the first trial only, NR were rewarded on the second trial only, while RR were rewarded on both trials. Alternation was approximately the same for all groups, and there was little decline in alternation over 28 days. There was, however, a difference in the choice behaviour on trials when rats failed to alternate, NR and RR, but not RN, choosing according to a position preference. These results are incompatible with several earlier theories of spontaneous alternation, and the hypothesis was put forward that alternation is initially part of an exploratory tendency, but that, when the maze becomes explored, the exploratory tendency dies down, and alternation only continues when rats have been reinforced (primarily or secondarily) for alternating. This hypothesis was tested in a second experiment, similar to the first but in which one group of rats was not rewarded on either trial; as predicted, this group showed significantly more decline in alternation than rewarded rats.     

Spontaneous and learned turning behaviour in food- or water-restricted hooded rats

Some laboratory studies have suggested that whereas food restriction in animals leads to response alternation (behavioural flexibility), water restriction induces perseverative, stereotyped responding. Hooded rats, restricted to 1 hour per day access to either food or water, were tested on a radial-arm maze (using a procedure that eliminates algorithmic response strategies), for alternation in a 3-arm maze (both when the maze was familar and unfamilar, and with or without differential reward) and a 2-choice maze in which some animals were taught to alternate direction of turn, and others to perseverate. Both groups performed the radial-arm maze task competently and spontaneously alternated at a high rate. In the learned task, food-restricted rats were slower than water-restricted to reverse a consistent direction of turn; in the alternation condition, water-restricted rats developed a temporary, but strong, directional bias when making their first choice each day. Water-restricted subjects took water more readily than food-restricted took food when initially introduced to the apparatuses, but there was no consistent difference in motivation in the two conditions. The results provide little support for the notion that distinct cognitive-motivational states or behavioural strategies are induced by food- and water-restriction.     

An assessment of response, direction and place learning by rats in a water T-maze

Behavioral data suggest that distinguishable orientations may be necessary for place learning even when distal cues define different start points in the room and a unique goal location. We examined whether changes in orientation are also important in place learning and navigation in a water T-maze. In Experiment 1, rats were trained to locate a hidden platform and given a no-platform probe trial after 16 and 64 trials with the maze moved to a new position. Direction and response strategies were more prevalent than a place strategy. In Experiment 2, acquisition of place, response and direction strategies was assessed in a water T-maze that was moved between two locations during training. Rats were impaired on the place task when the maze was translated (moved to the L or R) but were successful when the maze was rotated across trials. These data are consistent with findings from appetitive tasks.     

Rats' sensitivity to their direction of movement and spontaneous alternation behaviour

The response of rats to their prior direction of movement was examined in three spontaneous alternation experiments. In the first, a straight alley run interpolated between two T-maze trials increased goal arm alternation when it was in the same direction as that of the animal's first T-maze goal arm entry and decreased the alternation tendency when it was in the opposite direction. Experiment II found that multiple runs in one direction in a straight alley increased the likelihood that rats would subsequently enter the goal arm of a T-maze which permitted movement in an opposite direction. In the third experiment, rats entered those goal arms of an eight-arm radial maze which permitted movement in any direction which was different from that during a preceding straight alley trial. The results of these experiments indicate that rats are quite sensitive to their direction of movement and use it as a cue in guiding their behaviour in a variety of experimental situations.     

Impaired, spared, and enhanced ACh efflux across the hippocampus and striatum in diencephalic amnesia is dependent on task demands

Diencephalic amnesia manifests itself through a host of neurological and memory impairments. A commonly employed animal model of diencephalic amnesia, pyrithiamine-induced thiamine deficiency (PTD), results in brain lesions and impairments similar in nature and distribution to those observed in humans with Wernicke–Korsakoff syndrome (WKS). In the current investigation, 2 separate experiments were conducted in which acetylcholine (ACh) efflux was assessed in the hippocampus and striatum of PTD-treated and pair-fed (PF) control male Sprague–Dawley rats. The goal was to determine under what behavioral conditions and in which brain structures ACh efflux was spared, impaired, or adaptively enhanced. In Experiment 1, rats were assessed on a spontaneous alternation task; in Experiment 2, rats were tested on a T-maze discrimination task that could be learned via a hippocampal- or striatal-based strategy. In Experiment 1, PTD-treated rats were impaired on the spontaneous alternation task and ACh efflux in the hippocampus during testing was significantly reduced, but spared in the striatum. In Experiment 2, PTD- and PF-treated rats did not differ in the number of trials to criterion, but PTD-treated rats demonstrated greater reliance upon egocentric cues to solve the task. Furthermore, ACh efflux in the striatum was greater during maze learning in the PTD-treated animals when compared to the PF animals. These results suggest that there is behavioral and systems level plasticity that can facilitate the use of alternative strategies to solve a task following diencephalic damage and WKS.     

Involvement of the medial prefrontal cortex in two alternation tasks using different environments

Spatial alternation performance in rats is usually evaluated with the T-Maze. The first aim of this study was to analyze the effect of a selective lesion of medial prefrontal cortex (mPFC) on performance in a T-maze. Second, we wanted to validate a new test using alternation in a water maze (AWM). The mPFC of 21 male Sprague-Dawley rats was lesioned bilaterally using in situ microinjection of ibotenic acid. Thirteen control rats received injections of the vehicle only. Results show that mPFC lesioned rats were significantly impaired in the T-Maze as well as in the AWM compared to controls. These results validate the AWM as a frontal cortex dependent task probing working memory and/or behavioral flexibility. We suggest that the AWM may be more powerful than the T-maze as an investigational tool, given that is can be easily compared to other water maze tasks that evaluate other (nonfrontal) cognitive modules.     

Contributions of the dorsal hippocampus and the dorsal subiculum to processing of idiothetic information and spatial memory

It is well established that the dorsal hippocampal formation is crucial for spatial memory in rats. However, little is known about the distinct functions of the dorsal hippocampus and the dorsal subiculum. To examine the role of the dorsal hippocampus and the dorsal subiculum, Long-Evans rats with excitotoxic lesions (NMDA) of the dorsal hippocampus (DH), the dorsal subiculum (DS), or both (DHDS), and controls were trained on a nonmatching-to-place task. Then, to identify the strategy used by each group, they were tested on the same task in the dark with the T-maze being rotated between the sample and the test runs. In the light, rats with combined lesions were impaired. In the dark, groups DH, DS, and controls performed near chance level except in trials without rotation, suggesting the use of a sense of direction. The same rats were trained on a radial-arm maze task. In the light, where proximal visual cues were accessible, combined lesions affected performance whereas in the dark, it was impaired by all lesions. This experiment demonstrated that the dorsal subiculum and the dorsal hippocampus play a crucial role in processing idiothetic information and/or in maintenance of this information in memory.     

Comparison of effects of small lesions in posterodorsal septum on spontaneous and rerun correction (contingently reinforced) alternation in rats.

In the first part of the experiment, characteristics of T-maze alternation behavior were compared by giving one group of 11 rats seven sessions under conditions of "rerun correction" (contingent reinforcement for alternation) and another group of 11 rats the same number of sessions with noncontingent reinforcements, i.e., entering either goal arm of the T-maze was reinforced. Both groups alternated significantly above chance, and the difference in medians between groups was small but significant in later sessions. However, rats given rerun correction training quickly came against the "ceiling" of 100% alternation, and individual differences were small. The scores of rats run under conditions of "spontaneous" alternation were more variable, both within and between rats. In the second part of the experiment, six rats in each group received small electrolytic lesions in the posterodorsal septum. There were five operated-control rats from each group. After 2-wk postoperative recovery all rats were again given seven sessions in the T-maze. Under rerun correction procedure (contingent reinforcement), the controls retained near-perfect alternation scores. Most animals with lesions dropped to chance levels but recovered to control level over the seven sessions. Rats tested under spontaneous alternation conditions behaved quite differently. The control group continued to alternate significantly, but rats with lesions significantly alternated less and did not recover.     

Proactive interference and spontaneous alternation in rats

Two pairs of trials were given to naive rats in a T-maze. The first trial of a pair was forced to one arm, the second was free, and the delay between trials was 25 min. or 10 hr. Rats left in the maze for 15 sec. following the forced choice showed increased alternation on the second pair of trials at the 25-min. delay as compared with the 10-hr. delay. This was interpreted as due to a decline in alternation with delay on this pair of trials, together with an overall increase in alternation between the first and second pairs, and is consistent with the proactive interference theory of forgetting. Rats left in for 2 min. showed a decline in alternation with delay on the first pair of trials, but not on the second; this is inconsistent with the proactive interference theory.     

Reduced spiking in entorhinal cortex during the delay period of a cued spatial response task

Intrinsic persistent spiking mechanisms in medial entorhinal cortex (mEC) neurons may play a role in active maintenance of working memory. However, electrophysiological studies of rat mEC units have primarily focused on spatial modulation. We sought evidence of differential spike rates in the mEC in rats trained on a T-maze, cued spatial delayed response task. Animals begin at the base of the T-maze where a 1-sec white noise and visual light cue are presented on the left or right side of the maze. Rats are rewarded for responding toward the cued direction. In correct trials, we observed decreased spike rates during the delay period, the time interval between cue presentation and reward delivery. Firing-rate histograms show significant decreases during the delay period compared to 5-sec windows from both pre-cue and post-reward periods. We analyzed how running speed and trajectory specificity correlated to spike rate. Twice as many cells were responsive to cue alone compared to running speed. Trajectory specificity did not relate significantly to firing rate. Decreased spike rate may reflect active maintenance in other structures inhibiting mEC. Alternately, the reduction may reflect decreases in background activity during enhanced attention and cholinergic modulation. Lastly, animals often ran through the T-maze choice-point with varying speed. We calculated the spatial posterior probability density from spike rates during these choice-point passes. Slow passes through the choice point were characterized by greater probability of decoding to the reward locations on correct trials compared to quick passes on the maze consistent with similar "look-ahead" properties previously reported in the hippocampus and ventral striatum.     

Spontaneous alternation behavior in hamsters

Male and female golden hamsters spontaneously alternated successive entries of T-maze arms (derived from a + − maze) rather than body turns during a series of eight consecutive trials except when not confined to the arm chosen on each trial. Only unconfined males failed to alternate on their first opportunity. Confinement to an entered arm for 30 seconds had no effect on females but increased alternation in males. Increasing the visual discriminability of the arms had no effect on alternation in either sex. It was concluded that spontaneous alternation behavior in hamsters depended upon whether or not they were confined to a chosen arm and their sex. It is possible that the phenomenon was escape-related.     

Food priming and short-term retention in the delayed alternation task

The delayed alternation task, with rats as subjects, was used to assess the effects of a priming food reward on subsequent retention of a reinforced target location in a T maze. Subjects received a pretrial feeding, followed by a forced-choice rewarded entry into one goal box of the maze (the “cuing” run). Following a delay interval (5–60 s), the subjects were allowed to choose either goal, with reward available only in the one not entered on the cuing run. Priming significantly reduced such alternation after 30- and 60-s delays (Experiment 1), whereas administering the reward following the cuing run had no effect on choice behavior (Experiment 2). In the third study, prefeeding had a decremental effect when the following cuing run was reinforced, but no decrement occurred when reinforcement was omitted on the cuing run. The results suggest that food reward enhances retention of spatial information, but priming reduces this effect.     

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.     

The overtraining reversal effect in rats: A function of task difficulty

Two experiments were conducted with rats. The first study showed that in the T-maze a brightness discrimination learning problem was more difficult than a spatial learning problem, but in a Ross-maze a brightness problem was less difficult than a spatial task. T-maze brightness and Ross-maze spatial tasks were found to be of equal difficulty.

In the second experiment rats were trained either on a brightness or spatial discrimination reversal problem in the Ross-maze. It was found that overtraining facilitated reversal performance in the spatial task but not in the brightness problem. The theoretical implications of these results were discussed.     

Anisomycin impairs long-term working memory in a delayed alternation task

A long-term temporal component of working memory of rats trained on the radial maze has been shown to be susceptible to disruption by the protein synthesis inhibitor, anisomycin. It is not clear whether protein synthesis played a role in working memory because accurate performance on the radial maze required the storage of a large amount of information, or because the information was to be held in store for relatively long periods of time. This experiment tested these hypotheses by assessing the effect of anisomycin on choice accuracy in a comparatively simple spatial delayed alternation task. Results indicate that under the present training conditions, protein involvement in working memory is related more to the length of the retention interval than to the amount of information retained.     

Effects of anterior or dorsomedial thalamic ibotenic lesions on learning and memory in rats

Sprague-Dawley rats were used to study the effects of ibotenic acid lesions of the anterior (A.Th.) and the dorsomedial (MD) thalamic nuclei on learning and memory. Memory was assessed by employing a temporal alternation task in a straight alley with varying intertrial intervals. In addition, spatial orientation and response flexibility were evaluated on a radial maze and on a spatial reversal task (SSDR). The results indicated that MD rats required more trials to learn the temporal alternation task and exhibited impaired performance compared to A.Th. and control groups at the shortest delay (15 s). In contrast, compared to the control group, A.Th. subjects which required less trials to master the task and exhibited normal performance at the 15-s delay were impaired when the intertrial interval was increased to 45 s. Whatever the lesion, no impairments were found in the SSDR or the radial maze while only MD lesions were found to result in a night hyperactivity associated with greater food and water consumptions. These findings indicate that A.Th. and MD are differentially involved in learning and memory processes. It is suggested that the MD is mostly involved in registering new information while the A.Th. plays a role in the maintenance of information over time.     

Fetal Alcohol-Exposed Rats Exhibit Differential Response to Cholinergic Drugs on a Delay-Dependent Memory Task

Fetal alcohol exposure in human and rodents produces a number of cognitive deficits including impairments in learning and memory. Recent evidence in our laboratory has shown that fetal alcohol-exposed (FAE) rats respond differently to systemic administration of cholinergic drugs when tested for vigilance and locomotor activity. The present study examined the effects of muscarinic and nicotinic agonists and antagonists on memory performance in a delayed alternation task. Subjects were male offspring of Sprague-Dawley rats fed a 35% ethanol-derived caloric diet, pair-fed with sucrose, or chow-fed with lab chow during the last 2 weeks of gestation. Rats (3 months old) were food-deprived prior to training in the T-maze. Rats were first trained in the alternation task at no delay for five sessions. Rats were then trained at longer delays (20, 60, 180 s) until all groups showed similar performance for two consecutive sessions. Each animal was then tested following systemic injections of the cholinergic antagonists scopolamine and mecamylamine (60-s delay) and the cholinergic agonists pilocarpine and nicotine (180-s delay). Rats received saline injections on alternate days of testing. The results revealed that FAE rats exhibited no impairments in alternation performance at the no delay and 20-s delay, but showed impairments on both the 60- and 180-s delays during the initial sessions. However, with additional training, FAE rats showed performance similar to that of control groups at these delays. Following both pilocarpine and nicotine injections, control groups, but not the FAE group, showed significant memory enhancement in the alternation task. Following scopolamine injections, the FAE rats showed a significant impairment, while control groups showed a nonsignificant decrease in performance. All three groups showed impairments in the alternation task following administration of mecamylamine compared to saline treatment. These findings suggest that alterations in the cholinergic system in FAE rats may underlie some of the cognitive deficits observed with prenatal alcohol exposure.     

Cognitive performances and locomotor activity following dentate granule cell damage in rats: role of lesion extent and type of memory tested

Intradentate injection of colchicine is one of the techniques used to destroy granule cells. This study compared the behavioral effects of various amounts of colchicine (1.0, 3.0, and 6.0 microg; Col 1, Col 3, and Col 6, respectively) injected into the dentate gyrus of adult Long-Evans male rats. Starting 10 days after lesion surgery, behavioral testing assessed home-cage and open-field locomotion, alternation in a T-maze, water-maze, and radial-maze learning according to protocols placing emphasis on reference, and working memory. All of these tasks are sensitive to hippocampal disruption. Histological verifications showed that the extent of the lesions depends on the dose of colchicine (index of dentate gyrus shrinkage: -33% in Col 1, -54% in Col 3, and -67% in Col 6 rats). Colchicine dose-dependently increased nocturnal home cage activity (an effect found 10 days but not 5 months after surgery), but had no significant effect on open-field locomotion or T-maze alternation. A dose-dependent reference memory impairment was found during the acquisition of spatial navigation in the water maze; Col 3 and Col 6 rats were more impaired than Col 1 rats. During the probe trial (platform removed), control rats spent a longer distance swimming over the platform area than all rats with colchicine lesions. In the working memory version of the test, all rats with colchicine lesions showed significant deficits. The deficits were larger in Col 3 and Col 6 rats compared to Col 1 rats. The lesions had no effect on swimming speed. In the radial-maze test, there was also a dose-dependent working memory impairment. However, reference memory was disrupted in a manner that did not differ among the three groups of lesioned rats. Our data are in line with the view that the dentate gyrus plays an important role in the acquisition of new information and is an integral neural substrate for spatial reference and spatial working memory. They also suggest that damage to granule cells might have more pronounced effects on reference than on working memory in the radial maze. Finally, they demonstrate that part of the variability in the conclusions from previous experiments concerning the role of granule cells in cognitive processes, particularly in spatial learning and memory, may be due to the type of tests used and/or the extent of the damage produced.