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.     

Training method dramatically affects the acquisition of a place response in rats with neurotoxic lesions of the hippocampus.

A considerable number of studies have demonstrated that hippocampal damage impairs the acquisition of a place response in rats. In Experiment 1, using a four-arm plus-shaped maze, we replicated this finding. Experiment 2 showed, however, that hippocampally damaged rats can learn a place response just as well as control rats when, during the training, a salient intramaze landmark indicates the position of the goal (the west arm). After reaching criterion, the hippocampal and control groups performed the task with the same degree of mastery during a transfer test in which the intramaze signal used during the acquisition was removed. In Experiment 3, the intramaze cue was substituted by an egocentric cue. The results revealed that both control and lesioned subjects learned the spatial problem well. However, a transfer test showed that control rats learned the task using a place response strategy but hippocampally lesioned animals used a rigid, hyperspecific strategy. Taken together, these results suggest that special training procedures which encourage variability in response versus perseveration make it possible to overcome the acquisition deficit normally observed in hippocampal rats.     

Development of spatial memory and spatial orientation in preschoolers and primary school children

The present study addresses the question of what kind of information children use when orientating in new environments, if given proximal and distal landmarks, and how spatial memory develops in the investigated age groups. Ten 5-year-old, ten 7-year-old and ten 10-year-old children were presented with the ‘Kiel Locomotor Maze’, containing features of the Radial Arm Maze and the Morris Water Maze, in order to assess spatial memory and orientation. Children had to learn to approach baited locations only. Task difficulty was equated with respect to the children's age. Training was given until the children reached criterion. During testing, the maze configuration and response requirements were systematically altered, including response rotation, cue rotation, cue deletion and response rotation with cue deletion in order to assess the spatial strategies used by the children. During training and testing, working-memory errors (WM), reference-memory errors (RM) and working-reference memory errors (WR) were recorded. As expected, no difference between age groups appeared during training, thus confirming comparable task difficulty across age groups. During testing, age groups differed significantly with regard to the orientation strategy used. The 5-year-olds were bound to a cue strategy, orientating towards local, proximal cues. The 10-year-olds mastered all tasks, thus displaying a place strategy, being able to use distal cues for orientation, and were even able to do so after being rotated 180°. The 7-year-olds proved to be at an age of transition: five of them were bound to a cue strategy, five children were able to adopt a place strategy. The differences in the orientation strategies used by children of different age groups was reflected by the sum of errors they made, also by RM. WM were found to be rare, especially in older children. We conclude that preschoolers use a cue strategy, that the development of place strategies occurs during primary school age and seems to be complete by the age of 10 years.     

Preserved learning about allocentric cues but impaired flexible memory expression in rats with hippocampal lesions

Several studies have shown that slight modifications in the standard reference spatial memory procedure normally used for allocentric learning in the Morris water maze and the radial maze, can overcome the classic deficit in allocentric navigation typically observed in rats with hippocampal damage. In these special paradigms, however, there is only intramaze manipulation of a salient stimulus. The present study was designed to investigate whether extramaze manipulations produce a similar outcome. With this aim a four-arm plus-shaped maze and a reference spatial memory paradigm were used, in which the goal arm was marked in two ways: by a prominent extramaze cue (intermittent light), which maintained a constant relation with the goal, and by the extramaze constellation of stimuli around the maze. Experiment 1 showed that, unlike the standard version of the task, using this special training procedure hippocampally-damaged rats could learn a place response as quickly as control animals; importantly, one day after reaching criterion, lesioned and control subjects performed the task perfectly during a transfer test in which the salient extramaze stimulus used during the acquisition was removed. However, although acquisition deficit was overcomed in these lesioned animals, a profound deficit in retention was detected 15 days later. Experiment 2 suggests that although under our special paradigm hippocampal rats can learn a place response, spatial memory only can be expressed when the requisites of behavioral flexibility are minimal. These findings suggest that, under certain circumstances, extrahippocampal structures are sufficient for building a coherent allocentric representation of space; however, flexible memory expression is dependent, fundamentally, on hippocampal functioning.     

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.     

Spatial Working Memory and Reference Memory of Brown Norway and WAG Rats in a Holeboard Discrimination Task

To determine whether working memory (WM) and reference memory (RM) represent different aspects of spatial memory, albino WAG rats and the pigmented Brown Norway rats were tested in the acquisition, retention, and reversal of spatial orientation tasks in the holeboard, which allows the simultaneous assessment of WM and RM. Putative nonmnemonic factors, such as the speed of visiting the holes or the development of a search strategy (preferred sequence of visiting the baited set of holes) were also evaluated because they might influence WM and RM performance. The WM performance of Brown Norway rats was generally worse than that of the WAG rats. The reverse was true for the RM performance. Correlation analysis supported the notion that these two measures are independent. Differences in the speed of visiting the holes and in the development of a preferred sequence of visiting the baited set of holes could not explain the strain differences in WM and RM performance. Because spatial WM and RM appear to be independent measures in the holeboard, this task could be used to investigate whether different neural substrate(s) underlie these two memory components.     

The medial prefrontal cortex and memory of cue location in the rat

We developed a single-trial cue-location memory task in which rats experienced an auditory cue while exploring an environment. They then recalled and avoided the sound origination point after the cue was paired with shock in a separate context. Subjects with medial prefrontal cortical (mPFC) lesions made no such avoidance response, but both lesioned and control subjects avoided the cue itself when presented at test. A follow up assessment revealed no spatial learning impairment in either group. These findings suggest that the rodent mPFC is required for incidental learning or recollection of the location at which a discrete cue occurred, but is not required for cue recognition or for allocentric spatial memory.     

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.     

The roles of the medial prefrontal cortex and hippocampus in a spatial paired-association task

Although the roles of both the hippocampus and the medial prefrontal cortex (mPFC) have been suggested in a spatial paired-associate memory task, both areas were investigated separately in prior studies. The current study investigated the relative contributions of the hippocampus and mPFC to spatial paired-associate learning within a single behavioral paradigm. In a novel behavioral task, a pair of different objects appeared repeatedly across trials, but in different arms in a radial maze, and different rules were associated with those arms for reward. Specifically, in an "object-in-place" arm, the rat was required to choose a particular object associated with the arm. In a "location-in-place" arm, the animal was required to choose a certain within-arm location (ignoring the object occupying the location). Compared to normal animals, rats with ibotenic acid-based lesions in the hippocampus showed an irrecoverable impairment in performance in both object-in-place and location-in-place arms. When the mPFC was inactivated by muscimol (GABA(A) receptor agonist) in the normal animals with intact hippocampi, they showed the same severe impairment as seen in the hippocampal lesioned rats only in object-in-place arms. The results confirm that the hippocampus is necessary for a biconditional paired-associate task when space is a critical component. The mPFC, however, is more selectively involved in the object-place paired-associate task than in the location-place paired-associate task. The current task powerfully demonstrates an experimental situation in which both the hippocampus and mPFC are required and may serve as a useful paradigm for investigating the neural mechanisms of object-place association.     

Dissociation of Hippocampal and Striatal Contributions to Spatial Navigation in the Water Maze

Two experiments were conducted to compare the effects of fornix/fimbria and caudate-putamen lesions in Long–Evans hooded rats (Rattus norvegicus) trained on two water maze tasks that differed in the type of spatial localization required for optimum solution. In Experiment 1, the lesioned rats and surgical controls were trained on the standard place task in the water maze (Morris, 1981) and given two postacquisition tests (a platform removal probe and platform relocation test). In Experiment 2, rats with similar lesions and control rats were trained on a modified cue navigation task. Fornix/fimbria lesions impaired a late stage of place task acquisition but did not impair acquisition of the cue task. Caudate-putamen lesions resulted in a severe place acquisition impairment and a transient cue acquisition impairment, both of which were characterized by an initial tendency to swim near the wall of the pool. Post-hoc analyses of the direction and angles of departure from the start points suggested that rats with fornix/fimbria lesions used non-allocentric spatial strategies to solve the place task. These rats also demonstrated a significantly weakened spatial bias for the former training quadrant on the platform removal probe and reduced flexibility in navigating to a novel platform location on the platform relocation test. In contrast, rats with caudate-putamen lesions showed a significant spatial bias for the former training quadrant but failed to cross the exact location within the quadrant where the platform was formerly positioned. The results suggest that the hippocampus mediates the allocentric spatial component of the water maze place task while the dorsomedial striatum may play an important role in the acquisition of the procedural aspects of both place and cue versions of the task.     

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 extent of working memory deficits associated with Williams syndrome: exploration of verbal and spatial domains and executively controlled processes

The present study investigated verbal and spatial working memory (WM) functioning in individuals with the neuro-developmental disorder Williams syndrome (WS) using WM component tasks. While there is strong evidence of WM impairments in WS, previous research has focused on short-term memory and has neglected assessment of executive components of WM. There is a particular lack of consensus concerning the profile of verbal WM functioning in WS. Here, WS participants were compared to typically developing participants matched for (1) verbal ability and (2) spatial ability (N = 14 in each of the 3 groups). Individuals with WS were impaired on verbal WM tasks, both those involving short-term maintenance of information and executive manipulation, in comparison to verbal-matched controls. Surprisingly, individuals with WS were not impaired on a spatial task assessing short-term maintenance of information in memory (remembering spatial locations) compared to spatial-matched controls. They were, however, impaired on a spatial executive WM task requiring the manipulation of spatial information in memory. The present study suggests that individuals with WS show WM impairments that extend to both verbal and spatial domains, although spatial deficits are selective to executive aspects of WM function.     

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 memory and radial arm maze performance of rats

Rats were tested on an elevated radial maze for their ability to choose each of 17 different arms once without repeating any choices. The first experiment indicated that the animals performed well, choosing an average of more than 14 different arms in the first 17 choices. Subsequent experiments demonstrated that: (a) response patterns, general algorithms, or intramaze markings were not necessary for correct choices: (b) there was interference among choices within a test so that the probability of a correct response decreased as the number of choices increased; (c) there was no serial-order effect (primacy or recency); (d) animals tested in a procedure which did not require prior shaping showed no evidence of a general predisposition not to repeat choices. The results are discussed in terms of capacity, accuracy, and other characteristics of working spatial memory.     

Remodeling of hippocampal mossy fibers is selectively induced seven days after the acquisition of a spatial but not a cued reference memory task

Relating storage of specific information to a particular neuromorphological change is difficult because behavioral performance factors are not readily disambiguated from underlying cognitive processes. This issue is addressed here by demonstrating robust reorganization of the hippocampal mossy fiber terminal field (MFTF) when adult rats learn the location of a hidden platform but not when rats learn to locate a visible platform. Because the latter task requires essentially the same behavioral performance as the former, the observed MFTF growth is seen as the consequence of specific input-dependent hippocampal activity patterns selectively generated by processing of extramaze but not intramaze cues. Successful performance on the hidden platform task requires formation of spatial memory. Increased MFTFs in hidden platform-trained rats are observed 7 d but not 2 d after training nor in swim controls. These results suggest that structural plasticity of the mossy fiber:CA3 circuit may contribute to the maintenance of long-lasting memory but not to the initial storage of the spatial context.     

Working memory encoding and false memory in schizophrenia and bipolar disorder in a spatial delayed response task

Working memory (WM) impairment is a core feature of schizophrenia, but the contributions of different WM components are not yet specified. Here, we investigated the potential role of inefficient encoding in reduced WM performance in patients with schizophrenia (PSZ). Twenty-eight PSZ, 16 patients with bipolar disorder (PBP), 16 unaffected and unmedicated relatives of PSZ (REL), and 29 demographically matched healthy controls (HC) performed a spatial delayed response task with either low or high WM demands. The demands on attentional selection were also manipulated by presenting distractor stimuli during encoding in some of the trials. After each trial, participants rated their level of response confidence. This allowed us to analyze different types of WM responses. WM was severely impaired in PSZ compared to HC; this reduction was mainly due to an increase in the amount of false memory responses (incorrect responses that were given with high confidence) rather than an increase in the amount of incorrect and not-confident responses. Although PBP showed WM impairments, they did not have increased false memory errors. In contrast, reduced WM in REL was also accompanied by an increase in false memory errors. The presentation of distractors led to a decline in WM performance, which was comparable across groups indicating that attentional selection was intact in PSZ. These findings suggest that inefficient WM encoding is responsible for impaired WM in schizophrenia and point to differential mechanisms underlying WM impairments in PSZ and PBP. (PsycINFO Database Record (c) 2012 APA, all rights reserved).     

Those cheating rats: male and female rats use odor trails in a water-escape "working memory" task.

Three-month-old Sprague-Dawley rats were trained on a working memory win-stay (spatial delayed matching-to-sample) water-escape task with the escape platform location the same for all subjects on a given trial, a procedure that maximizes the buildup of an odor trail to the escape platform. In subsequent tests during which the location of the escape platform varied randomly between subjects, the rats, especially the females, while continuing to perform above chance level, made increased errors. Varying the platform location between subjects eliminated odor trail as a nonambiguous cue for locating the escape platform. In a second experiment females performed better than males on a reference memory odor trail discrimination task which involved following the path of like-gender "pathmaker" rats to the escape platform. The relatively poor use of odor trails by the males was associated with a high frequency of choosing a preferred choice section or returning to the choice section selected first on the immediately preceding trial (perseveration). Collectively, the two experiments demonstrate that rats can use either working memory or odor trails to locate an escape platform in a water maze, and that they, especially females, will use odor trails in a working memory task if odor trails are available. Clearly, the location of the escape platform should be varied randomly between subjects in tests of working memory.     

Testosterone fails to reverse spatial memory decline in aged rats and impairs retention in young and middle-aged animals

Recently, the vasopressin (AVP) innervation in the rat brain was shown to be restored in senescent rats following long-term testosterone administration. In order to investigate whether this restoration is accompanied by an improvement in learning and memory, both sham- and testosterone-treated young (4.5 months), middle-aged (20 months), and aged (31 months) male Brown-Norway rats were tested in a Morris water maze. All animals learned to localize a cued platform equally well, indicating that the ability to learn this task was not affected by sensory, motoric, or motivational changes with aging or testosterone treatment. There were no significant differences in retention following cue training. Subsequent training with a hidden platform in the opposite quadrant of the pool (place training) revealed impaired spatial learning in middle-aged and aged animals. Retention following place training was significantly impaired in the sham-treated aged rats as compared with sham-treated young rats. Testosterone treatment did not improve spatial learning nor retention of spatial information, but, on the contrary, impaired retention in young and middle-aged animals. The present results confirm earlier reports on an impairment of spatial learning and memory in senescent rats but fail to support a role of decreased plasma testosterone levels and central AVP innervation in this respect.     

Intraseptal administration of muscimol produces dose-dependent memory impairments in the rat

The present study examined the effects of intraseptal administration of the GABAergic agonist muscimol on performance of a radial-arm maze (RAM) task. Male Long-Evans rats were trained to perform a RAM task in which a 1-h delay was imposed between the sample and the test session. In this task rats have access to four out of eight maze arms during a predelay session. Following a 1-h delay, rats are returned to the maze and allowed to freely choose among all eight arms. Arms not blocked during the predelay session are baited, and entry into an arm chosen during the predelay session or a repeated entry into a postdelay chosen arm constitutes an error. Following acquisition, animals were implanted with a single cannula aimed at the medial septum. A within-subjects design was utilized to examine the effects of intraseptal administration of muscimol (0.0, 0.75, 1.5 or 3.0 nmol) on performance in this task. All drugs or artificial cerebrospinal fluid were administered immediately following the predelay session. Muscimol, a GABA-A agonist, produced a dose-dependent impairment in maze performance as evidenced by fewer correct choices in the first four postdelay choices and an increase in the number of errors. Intraseptal administration of muscimol did not significantly alter latency per choice on the RAM task nor did it affect locomotor activity levels. Muscimol-induced impairments were also observed when a 4-h delay was imposed between the fourth and the fifth maze selection, suggesting that the behavioral deficit represents an inability to store or retain spatial working memories rather than a general performance deficit. These data indicated that pharmacological manipulation of GABA-A receptors within the medial septum modifies working memory processes. The potential interaction of GABAergic and cholinergic mechanisms in the modulation of working memory processes is discussed.