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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 degrees 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.

Animals↗

Exploration of virtual mazes by rhesus monkeys (Macaca mulatta).

A chasm divides the huge corpus of maze studies found in the literature, with animals tested in mazes on the one side and humans tested with mazes on the other. Advances in technology and software have made possible the production and use of virtual mazes, which allow humans to navigate computerized environments and thus for humans and nonhuman animals to be tested in comparable spatial domains. In the present experiment, this comparability is extended even further by examining whether rhesus monkeys (Macaca mulatta) can learn to explore virtual mazes. Four male macaques were trained to manipulate a joystick so as to move through a virtual environment and to locate a computer-generated target. The animals succeeded in learning this task, and located the target even when it was located in novel alleys. The search pattern within the maze for these animals resembled the pattern of maze navigation observed for monkeys that were tested on more traditional two-dimensional computerized mazes.

Animals↗

Arm width and brightness modulation of spontaneous behaviour of two strains of mice tested in the elevated plus-maze.

Amongst the nonpharmacological variables that may influence spontaneous behaviour in the elevated plus-maze, at least two (namely, the width and brightness level of the maze arms) have not been evaluated for possible consequences on baseline activity. We therefore investigated the effect of width (5, 7, or 9 cm) and brightness level (grey vs. white) of the maze arms on the activity patterns of NMRI and C57/BL 10j mice in a plus-maze based on that described by Lister. Results indicated a clear strain difference in spontaneous behaviour in the open/closed arms with C57/BL mice making no visits on the open arms of the maze. In the NMRI strain, enlarging the arms resulted in significantly increased running in open arms but brightness level did not affect behavioural parameters. In the C57/BL mice, no significant behavioural changes were detected after increasing the arm width; however, the maze with a white floor significantly increased the latency to move and decreased ambulation. Finally, employing a maze with white closed arms and open grey arms resulted in ambulation by C57/BL mice into the open arms, a behaviour not normally observed in this strain using a uniformly bright maze. The results are discussed in terms of their putative effects in pharmacological testing.

Animals↗

Definition of a new maze paradigm for the study of spatial behavior in rats.

The present work defines a simple behavioral paradigm to evaluate spatial representation in rats. In two experimental conditions differing in the richness of distal visual cues, rats learned to locate a food goal in a cross maze from various starting points. We conducted different challenges consisting of (i) reaching the same goal from a modified arrangement of the maze arms (geometric challenge), (ii) reaching the goal within a 90 degrees rotated maze, herein checking the use of a place strategy, and (iii) investigating the effect of central cholinergic blockade over the retention of the task. Results showed that rats needed 12-30 trials to learn a place response, depending upon the richness of the visual environment. The maze rotation did not produce any impairment whereas the geometric challenge affected the performance specifically under the visually richer environment. Scopolamine injection (i.p.) produced a significant impairment in place recognition. Our present work shows that this maze procedure constitutes a useful paradigm to assess learning and processing of a place representation by rats. Similarly to what has been shown in other popular maze paradigms, our results show that rats mostly rely on distal extra-maze cues to solve the task, but also compute intra-maze information.

Animals↗

A computer vision-based automated Figure-8 maze for working memory test in rodents.

The benchmark test for prefrontal cortex (PFC)-mediated working memory in rodents is a delayed alternation task utilizing variations of T-maze or Figure-8 maze, which requires the animals to make specific arm entry responses for reward. In this task, however, manual procedures involved in shaping target behavior, imposing delays between trials and delivering rewards can potentially influence the animal's performance on the maze. Here, we report an automated Figure-8 maze which does not necessitate experimenter-subject interaction during shaping, training or testing. This system incorporates a computer vision system for tracking, motorized gates to impose delays, and automated reward delivery. The maze is controlled by custom software that records the animal's location and activates the gates according to the animal's behavior and a control algorithm. The program performs calculations of task accuracy, tracks movement sequence through the maze, and provides other dependent variables (such as running speed, time spent in different maze locations, activity level during delay). Testing in rats indicates that the performance accuracy is inversely proportional to the delay interval, decreases with PFC lesions, and that animals anticipate timing during long delays. Thus, our automated Figure-8 maze is effective at assessing working memory and provides novel behavioral measures in rodents.

Algorithms↗

Prior exposure to the elevated plus-maze sensitizes mice to the acute behavioral effects of fluoxetine and phenelzine.

A single undrugged experience of the elevated plus-maze modifies future drug responses in the test. The present study investigated the effects of maze-experience on the acute behavioral effects of the monoamine oxidase inhibitor phenelzine and the serotonin reuptake inhibitor fluoxetine. Phenelzine (2.5-12.5 mg/kg) had no clear effect on plus-maze behavior in test-naive Swiss Webster mice, but dose-dependently increased anxiety-like behavior in maze-experienced subjects. Similarly, fluoxetine (5-20 mg/kg) produced non-significant trends for increased anxiety-like behavior in maze-naive mice, but significantly and dose-dependently increased anxiety-like behavior and suppressed locomotor activity in maze-experienced mice. The anxiogenic effects of the benzodiazepine receptor inverse agonist N-methyl-beta-carboline-3-carboxamide (FG 7142) (20 mg/kg) was abolished by prior test experience, suggesting an alteration in gamma-aminobutyric acid (GABA)/benzodiazepine receptor function with maze-experience. However, the benzodiazepine receptor antagonist flumazenil (5-20 mg/kg) produced a silent profile regardless of maze-experience. Present findings provide further evidence demonstrating that prior test history is a critical consideration in mouse studies of anxiety-related behavior.

Animals↗

Chronic nicotinic agonist and antagonist effects on T-maze alternation.

A variety of studies have found that nicotine improves working memory function. However, other studies have either not found improvements or have found nicotine-induced deficits. The demands of the particular memory test may be critical for the expression of the nicotine effects. In several studies, we have found that chronic nicotine administration improves working memory performance in the radial arm maze. Chronic mecamylamine coadministration reversed this effect. The current study was conducted to determine the effects of chronic nicotine and mecamylamine on choice accuracy in a T-maze spatial alternation task. The same dose and duration of nicotine administration that we have previously found to significantly improve choice accuracy in the radial-arm maze was not effective in altering T-maze spatial alternation. The critical difference in task demands may be the presence with T-maze alternation of proactive interference. During a session, a choice alternative repeatedly changes valence from correct to incorrect and back again. In contrast, with the radial-arm maze as run in our studies, in a session the valence of an arm only changes once from correct to incorrect. Previous work with nicotine effects on spatial alternation in an operant task found evidence that nicotine increased the negative effect of proactive interference on performance. In the current study, chronic mecamylamine caused a significant deficit in T-maze spatial alternation. This same dose did not produce a deficit in the radial-arm maze and, in fact, caused an improvement during the first week of administration.

Animals↗

Chronic corticosterone impairs memory performance in the Barnes maze.

Chronic stress has been reported to impair spatial memory and cause hippocampal impairment in rodents. Glucocorticoids are believed to be the active agent in this impairment. Studies have demonstrated that chronic glucocorticoid administration results in animals being impaired in the Morris water maze (MWM) or eight-arm radial maze. Although both of these methods are well established means of testing spatial memory, neither might be considered optimal for studying the behavioral effects of stress. The Morris maze is itself highly stressful to the animals. The eight-arm maze relies on a food reward to motivate the animals, and glucocorticoids have profound effects on hunger and satiety. We therefore investigated behavioral deficits of corticosterone-treated animals in the two previously used mazes and the Barnes circular platform maze (BCM), a test similar in design to the Morris maze, but one that does not require the animal to perform a highly stressful swim. Consistent with results in other tests, we found that animals that had been treated for 3 months with stress-equivalent concentrations of glucocorticoids showed significantly impaired behavior in the Barnes maze.

Animals↗

Dose-response effect of docosahexaenoic acid ethyl ester on maze behavior and brain fatty acid composition in adult mice.

The dose-response effect of dietary docosahexaenoic acid (DHA, 22:6 n-3) ethyl ester (EE) on maze-learning ability in mice was studied. Male Crj:CD-1 mice aged three months were fed a) a diet containing 5 g palm oil/100 g diet (control group); b) a diet containing 0.5 g DHA ethyl ester/100 g diet plus 4.5 g palm oil/100 g diet (DHA-EE 0.5% group); c) a diet containing 1 g DHA ethyl ester/100 g diet plus 4 g palm oil/100 g diet (DHA-EEE 1% group); d) a diet containing 2 g DHA ethyl ester/100 g diet plus 3 g palm oil/100 g diet (DHA-EE 2% group) for four months. Maze-learning ability was assessed three months after the start of the experiment. The time required to reach the maze exit and the number of times that a mouse strayed into blind alleys in the maze were measured in three trials, performed every four days. In trial 1, the DHA-EE 0.5%, 1% and 2% groups required less (p < 0.05) time to reach the maze exit, and the DHA-EE 2% group strayed (p < 0.05) into blind alleys fewer times than the control group. In trial 3 performed four days after the second trial, the DHA-EE 2% group needed less (p < 0.05) time to find the exit and spent a fewer (p < 0.05) number of times in blind alleys than did the control group. In the total lipids of plasma and brain of mice fed DHA, increasing intakes of DHA resulted in an increase in DHA levels, with a corresponding decrease in arachidonic acid (20:4 n-6). Improved maze-learning ability in mice fed DHA-EE 2% was associated with higher DHA levels in brain. Our resulted suggest that there are no linear dose-response effects of DHA on maze-learning ability, however, the intake of DHA-EE 2% diet improves learning ability in adult mice as demonstrated by maze performance.

Animals↗

Changes in maze behavior of mice occur after sufficient accumulation of docosahexaenoic acid in brain.

The relationship between the time of intake of docosahexaenoic acid [DHA, 22:6(n-3)] and maze behavior in mice was studied. Male Crj:CD-1 mice (3 mo old) were fed a diet containing 2 g DHA-ethyl ester/100 g diet plus 3 g palm oil/100 g diet (DHA-EE group) or a diet containing 5 g palm oil/100 g diet (control group) for different periods of time. Maze-learning ability was assessed at 1 and 2 wk and 1 and 3 mo after the start of the control and experimental diets. In each maze-learning test, the time required to reach the maze exit and the number of times that a mouse strayed into blind alleys in the maze were measured in three trials, one every 4 d. After the last learning test in each trial, all mice were killed and the fatty acid compositions of plasma and brain lipids were determined. There were no significant differences in the results of the maze-learning tests between mice fed the diets at 1 or 2 wk in any of the three trials. After 1 and 3 mo, the DHA-EE diet groups required less time (P < 0.05) to reach the maze exit and strayed into blind alleys fewer times (P< 0.05) than did the control diet groups during trial 3. Significantly greater DHA levels were observed in the plasma and brain total lipids of the mice fed the DHA-EE diet after 2 wk, compared with those fed the control diet (P < 0.05), which was compensated for by lower arachidonic acid [20:4 (n-6)] levels. There were no significant differences in brain DHA levels among mice fed the DHA-EE diet for 2 wk, 1 mo, or 3 mo. Improved maze-learning ability after DHA intake was evident at 1 mo after the start of feeding and were maintained up to 3 mo, whereas the increased DHA levels in brain were apparent after feeding for just 2 wk. These results suggest that it may take time after the incorporation of DHA into the brain for improvement in learning ability to occur.

Animals↗

Spatial and nonspatial escape strategies in the Barnes maze.

The Barnes maze is a spatial memory task that requires subjects to learn the position of a hole that can be used to escape the brightly lit, open surface of the maze. Two experiments assessed the relative importance of spatial (extra-maze) versus proximal visible cues in solving the maze. In Experiment 1, four groups of mice were trained either with or without a discrete visible cue marking the location of the escape hole, which was either in a fixed or variable location across trials. In Experiment 2, all mice were trained with the discrete visible cue marking the target hole location. Two groups were identical to the cued-target groups from Experiment 1, with either fixed or variable escape locations. For these mice, the discrete cue either was the sole predictor of the target location or was perfectly confounded with the spatial extra-maze cues. The third group also used a cued variable target, but a curtain was drawn around the maze to prevent the use of spatial cues to guide navigation. Probe trials with all escape holes blocked were conducted to dissociate the use of spatial and discrete proximal cues. We conclude that the Barnes maze can be solved efficiently using spatial, visual cue, or serial-search strategies. However, mice showed a strong preference for using the distal room cues, even when a discrete visible cue clearly marked the escape location. Importantly, these data show that the cued-target control version of the Barnes maze as typically conducted does not dissociate spatial from nonspatial abilities.

Analysis of Variance↗

Prenatal ethanol exposure differentially alters behavior in males and females on the elevated plus maze.

Rodents prenatally exposed to ethanol demonstrate hypothalamic-pituitary-adrenal and behavioral hyperactivity to a variety of stressful situations. The present study examined both behavioral and corticosterone (CORT) responses to the elevated plus maze (+-maze), an anxiety- or fear-provoking task. Sprague-Dawley male and female offspring from fetal ethanol-exposed (E), pair-fed (PF), and ad libitum-fed control (C) groups were tested at 60 to 90 days of age. In experiment 1, behavior was measured in animals exposed to the +-maze for 5 min on two consecutive days; 2 weeks later, both behavioral and CORT responses were measured in animals confined to the open and closed arms of the maze for 20 min. In experiment 2, animals were placed in an open field (OF) for 5 min before a single 5-min exposure to the +-maze. Factor analysis of the scored behaviors from the two experiments indicated two main factors, designated "exploration" and "fear." E males and females both exhibited higher levels of exploratory behaviors when placed directly on the +-maze from their homecages without prior exposure to the OF, compared with C males and females. In addition, when confined to the closed arms of the +-maze, E males and females demonstrated higher levels of activity, compared with C males and females. After OF exposure, however, both E males and females demonstrated lower levels of exploratory behaviors than C males and females, and E females also had increased CORT levels, compared with PF and C females. Interestingly, E females, but not E males, showed an increase in fear-related behaviors on the +-maze, compared with controls, regardless of prior OF exposure. These data demonstrate that prenatal ethanol exposure may differentially affect both behavioral and hormonal responses of males and females in an aversive behavioral task and suggest that there may be a sex difference in the sensitivity of the mechanism(s) underlying these responses.

Animals↗

The effect of cul length and hippocampal lesions on maze learning in the rat.

Twenty-four rats, 8 with bilateral hippocampal lesions, 8 with cortical lesions and 8 unoperated rats, were tested on one of 2 mazes. Half of each group were run in a conventional 5 choice multiple Y maze. The other half were run in a symetrical, long cul maze in which distance and number of successive choice point were equal for a right or wrong choice before the animal reached an cul end or the goal box. The correct path in the long cul maze was identical to that of the short cul maze. S's were run one trial a day for 15 days. On the symetrical, long cul maze there were no differences between groups. On the short cul maze, hippocampals were significantly worse than control S's and looked similar to control S's on the long cul maze. The results are interpreted in terms of frustration theory.

Animals↗

Mental planning and anticipatory processes with acute and chronic frontal lobe lesions: a comparison of maze performance in routine and non-routine situations.

A series of computerized mazes were masked during presentation allowing only partial view of their structure. Patients suffering from acute or chronic unilateral frontal (medial, lateral) or retrorolandic (temporal, parietal) lesions and non-brain-damaged controls were required to pass through the mazes repeatedly, until they solved them without reaching a dead end. Because the mazes could not be viewed in their entirety at any one time, the subjects were forced to mentally generate and apply a plan of the maze. The first ("non-routine" situation), the second and the last ("routine" situation) trials of the mazes were analysed separately. The prefrontal cortex is supposed to subserve important functions in the planning of behaviour in unfamiliar, non-routine situations. Shallice (Phil. Trans. R. Soc. Lond. B298, 199-209, 1982; From Neuropsychology to Mental Structure, Cambridge University Press, Cambridge, 1988) therefore postulated that the behaviour of patients with frontal lobe lesions should not be disturbed in routine situations, but rather these patients should exhibit difficulties in dealing with new and unfamiliar situations. In the present investigation, patients with acute and chronic frontomedial lesions exhibited deficits in generating mental plans. Patients with acute frontomedial lesions made a larger number of errors in their second trials and subsequently required more trials to reach task criterium. Patients with chronic frontomedial lesions showed more frequent rule-breaking behaviour in their second trials. The analysis of maze performance in the first trial and that trial in which task criterion was achieved, showed that frontal lobe patients were impaired in neither routine nor non-routine situations. The observed results suggest a modification concerning Shallice's assumptions. Patients with frontomedial lesions are not generally incapable of dealing with non-routine situations. But they seem to be slower than patients with retrorolandic lesions and controls in profiting from experiences made in an unfamiliar, non-routine situation represented by the first explorations of new maze problems. This deficit can possibly be explained by the observation that anticipatory processes or the formation of expectations about possibly correct decisions in non-routine situations were altered in acute and chronic frontomedial patients. When these patients reached a maze intersection for the first time and therefore had no information about the continuation of the correct path, they showed significantly different intuitive directional decisions when compared to controls.

Adult↗

Parietal cortex lesions do not impair retention performance of rats in a 14-unit T-maze unless hippocampal damage is present.

Young male F-344 rats, pretrained in a straight runway to avoid shock, were then trained in a shock-motivated 14-unit T-maze. One day after maze acquisition, extensive parietal cortex lesions (PC) or sham operations (CON) were performed to assess possible involvement of parietal cortex in the age-related impairment previously observed in this task. Twelve days after surgery, a first 10-trial retention session in the 14-unit T-maze was conducted. One day later the vibrissae of half the rats in each group were clipped to examine involvement of the damaged barrel cortex field in maze performance of rats with PC lesions. The following day a second 10-trial retention session occurred. Finally, retention of the straight runway avoidance response was tested. Histological verification revealed a group with consistent parietal damage but also a subgroup with relatively small lesions to dorsal or lateral hippocampus in addition to parietal damage (PC + HIP). Behavioral results revealed virtually perfect maze retention for CON and PC rats. In contrast, PC + HIP rats were severely impaired in maze retention performance. Retention of the straight runway avoidance response was perfect in CON and PC rats but was impaired in PC + HIP rats. Vibrissae clipping did not affect error performance in the maze but led to a transitory increase in runtime. Overall, the results indicate that parietal lobe damage shortly after acquisition does not impair retention performance of young rats in the 14-unit T-maze, unless hippocampal damage is also evident. Thus, parietal lobe dysfunction alone would not appear to be involved in the age-related retention impairment previously observed in this task.

Aging↗

Synaptic density correlated with maze performance in young and aged rats. A preliminary study.

The aim of this study was to determine the effect of age both on maze performance and upon morphological changes in the brain. Young and senescent rats were differentiated into three groups by use of a complex 14-unit maze: young maze-bright rats, old maze-bright animals and old maze-dull rats. Layer III of the frontal and the occipital cortices of these animals was studied, employing coded electron micrographs, to determine the average number of synaptic profiles per area of thin section. It was observed that the young maze-bright rats had the highest synapse density, the old maze-bright rats had 85% of that amount while the old maze-dull animals had a density that was 54% that of the young animals.

Aging↗

Effects of amphetamine and beta-endorphin fragments on maze performance in rats.

Fragments of beta-endorphin and amphetamine cause similar effects in some tests of maze behavior in rats. The present study served to compare the influence of amphetamine and two beta-endorphin fragments [beta-endorphin (beta E)-(2-9) and beta E-(2-16)] on maze behavior in more detail. In Experiment I no significant effects of amphetamine and the peptides on behavioral performance in three selected Davenport configurations were found. In Experiment II amphetamine increased the frequency of errors and of returns to the start box, but only in the first trial. This effect was dependent on the rats' experience and on the maze configuration. In the next 11 trials, amphetamine slightly decreased the overall frequency of errors and of returns to the start box. Therefore, the effects of amphetamine on maze behavior depend upon the extent of training experience and on the structure of the test mazes. The peptides did not significantly affect maze performance. It is concluded that the effects of amphetamine and the beta-endorphin fragments on maze behavior are not comparable in this maze test.

Animals↗

Spatial working memory score of humans in a large radial maze, similar to published score of rats, implies capacity close to the magical number 7 +/- 22.

To compare the working memory (WM) capacity of humans to rats, we tested humans with a 17-arm radial maze and, in a follow up experiment, with a 13-arm radial maze. Both mazes were 15.2 meters in diameter, painted on a grassy field. In one version of the 13-arm experiment, we required a concurrent nonsense vocalization to impede subjects' use of language to remember locations. Subjects were instructed to choose arms of the radial maze unsystematically--as rats generally appear to do--and to visit the end of each arm only once. In additional procedures, we tested working memory capacity in a verbal task that is more analogous to the radial maze than is the typical ordered recall test. Subjects were asked to try to recite a sequence of 17 numbers (i.e., 18 through 34) or letters (A through Q) in unsystematic order, with no repeats. In another experiment subjects recited 13 numbers (14-26) or letters (A-M). In all tests, subjects were allowed only as many responses as there were distinct items (17 or 13, respectively). Average correct-response (nonrepeat) scores were 14.4 for the 17-arm maze and 14.1 for both of the verbal 17-item tests; these scores are close to the reported score for rats in a 17-arm radial maze. Average scores were between 10.8 and 11.4 in all of the 13-item maze and recitation tasks.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗