Exponential decay of spatial memory of rats in a radial maze

The persistence of spatial memory of rats (n = 14) was investigated in an eight-arm radial maze. The animals were trained until the mean number of errors in the first eight choices was 0.2. The decay of performance with time was studied using delays of 5, 20, 60, 120, or 240 min between choices 4 and 5, during which the animal was removed from the apparatus. A delay of 60 min significantly impaired performance. The mean number of errors was not significantly different from the random choice level after a delay of 120 min. The increase in the number of errors with time was exponential. Comparison of the results with those of previous studies suggests that the nature of training may have effects on memory persistence in the radial maze.     

Cholinergic-dopaminergic interactions in radial-arm maze performance

Although acetylcholine and dopamine are believed to play complementary roles in motor function, a comparable neurochemical interaction has not been established for cognitive function. The muscarinic receptor blocker scopolamine and the dopaminergic antagonist haloperidol have been found to impair choice accuracy of rats in the radial-arm maze. In the present study, low doses of these two drugs were administered intraperitoneally either alone or in combination to rats trained on a working memory task (food reward) in an eight-arm radial maze. Scopolamine, 0.125 mg/kg, produced a significant decrease in choice accuracy (i.e., arm entries until an error). Haloperidol, 0.0625 mg/kg, did not cause a significant decrease in accuracy, but there was a trend in that direction. The combination of haloperidol with scopolamine attenuated significantly the amnestic effect of scopolamine. These results suggest that, like motor behavior, cognitive function may be influenced by the balance between acetylcholine and dopamine.     

Radial-arm-maze behavior of the red-footed tortoise (Geochelone carbonaria)

The radial-arm maze is an established method for testing an animal's spatial win-shift behavior. Research on mammals, birds, and fish has shown that the mastery of this task is commonly mediated, to different degrees, by two types of strategy: those based on external cues and those based on response stereotypy. In the present study we trained four red-footed tortoises (Geochelone carbonaria) to navigate an eight-arm radial maze while providing different levels of access to visual room cues. The results indicate that response stereotypy is the more prevalent mechanism in these tortoises, although navigation based on landmarks can also occur if learned initially. The findings suggest that tortoise spatial navigation may be more similar to that observed in mammals and birds than previously thought.     

Effects of opiate antagonists on spatial memory in young and aged rats

The effects of post-training opiate antagonist administration on spatial memory were assessed in young and aged male Long Evans rats. In Experiment I rats were trained to visit each arm of an eight-arm radial maze once in a session to obtain a food reward placed at the end of each arm. During training aged rats required significantly more trials to achieve criterion performance when compared to young mature rats. However, administration of the opiate antagonist naloxone (2.0 mg/kg) immediately after each training trial did not significantly alter the rate of achieving accurate performance in either age group. In Experiment II young and aged rats that were previously trained to a comparable criterion on the radial maze were tested on the same maze apparatus in novel spatial environments. When animals were exposed to novel spatial information, the effects of post-trial opiate antagonists were examined using a within-subjects counter-balanced design. In Experiment IIa naloxone (2 mg/kg) enhanced the performance of both young and aged rats. In Experiment IIB naltrexone (1.0 mg/kg) was found to have a comparable effect of enhancing the performance of both age groups. In addition, in Experiment IIb a significant age-related deficit was found in rats tested in novel spatial environments. These results indicate that opiate antagonists are capable of improving memory for new spatial information in both young and aged rats on a task that is sensitive to behavioral deficits during normal aging.     

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.     

Persistent impairments in hippocampal function following a brief series of photoperiod shifts in rats

The impact of an acute circadian disruption on learning and memory in male and female rats was examined. Circadian disruption was elicited using a brief series of photoperiod shifts. Previous research using male rats showed that acute circadian disruption during acquisition of a spatial navigation task impaired long-term retention and that chronic circadian disruption impaired acquisition of the same task. However, the long-term effects of acute circadian disruption following circadian re-entrainment and whether sex differences in response to circadian disruption exist are still unknown. For the present study, rats were trained on the standard, spatial version of the Morris water task (MWT) and a visual discrimination task developed for the eight-arm radial maze. After reaching asymptotic performance, behavioural training was terminated and the experimental group experienced a series of photoperiod shifts followed by circadian re-entrainment. Following circadian re-entrainment, the subjects were given retention tests on the MWT and visual discrimination task. Following retention testing, an extra-dimensional shift using the eight-arm radial maze was also performed. An acute episode of circadian disruption elicited via photoperiod shifts negatively impacted retention of spatial memory in male and female rats. Retention of the visual discrimination task and the ability to detect extra-dimensional shifts were not impaired. The observed impairments on the MWT indicate that hippocampal representations are susceptible to a small number of photoperiod shifts even if the association is acquired prior to rhythm manipulation and retention is assessed following rhythm stabilization. Effects were limited to a hippocampus-dependent task, indicating that impairments are specific, not global.     

Longitudinal attentional engagement rescues mice from age-related cognitive declines and cognitive inflexibility

Learning, attentional, and perseverative deficits are characteristic of cognitive aging. In this study, genetically diverse CD-1 mice underwent longitudinal training in a task asserted to tax working memory capacity and its dependence on selective attention. Beginning at 3 mo of age, animals were trained for 12 d to perform in a dual radial-arm maze task that required the mice to remember and operate on two sets of overlapping guidance (spatial) cues. As previously reported, this training resulted in an immediate (at 4 mo of age) improvement in the animals' aggregate performance across a battery of five learning tasks. Subsequently, these animals received an additional 3 d of working memory training at 3-wk intervals for 15 mo (totaling 66 training sessions), and at 18 mo of age were assessed on a selective attention task, a second set of learning tasks, and variations of those tasks that required the animals to modify the previously learned response. Both attentional and learning abilities (on passive avoidance, active avoidance, and reinforced alternation tasks) were impaired in aged animals that had not received working memory training. Likewise, these aged animals exhibited consistent deficits when required to modify a previously instantiated learned response (in reinforced alternation, active avoidance, and spatial water maze). In contrast, these attentional, learning, and perseverative deficits were attenuated in aged animals that had undergone lifelong working memory exercise. These results suggest that general impairments of learning, attention, and cognitive flexibility may be mitigated by a cognitive exercise regimen that requires chronic attentional engagement.     

Enhanced visuospatial memory following intracerebroventricular administration of nerve growth factor

The present work assessed the effects of intracerebroventricular injections of rh recombined human nerve growth factor (rh NGF) (5 micrograms/2.5 microl) at postnatal days 12 and 13 upon the development of spatial learning capacities. The treated rats were trained at the age of 22 days to escape onto an invisible platform at a fixed position in space in a Morris navigation task. For half of the subjects, the training position was also cued, a procedure aimed at facilitating escape and at reducing attention to the distant spatial cues. Later, at the age of 6 months, all the rats were trained in a radial-arm maze task. Treatment effects were found in both immature and adult rats. The injection of NGF improved the performance in the Morris navigation task in both training conditions. There was a significant reduction in the escape latency and an increased bias toward the training platform quadrant during probe trials. The most consistent effect was the precocious development of an adult-like spatial memory. In the radial-arm maze, the NGF-treated rats made significantly fewer reentries than vehicle rats and this effect was particularly marked in the treated female rats. Taken together, these experiments reveal that the development and the maintenance of an accurate spatial representation are tightly related to the development of brain structures facilitated by the action of NGF. Moreover, these experiments demonstrate that an acute pharmacological treatment that leads to a transient modification in the choline acetyltransferase activity can induce a behavioral change long after the treatment.     

Intraseptal administration of bicuculline produces working memory impairments in the rat.

Male Sprague-Dawley rats, trained to perform a delayed-non-match-to-sample eight-arm radial maze task, were implanted with a single cannula aimed at the medial septal nucleus. A within-subjects design was utilized to examine the effects of intraseptal administration of bicuculline (0.5 micrograms) on performance of this task with 1- and 4-h delay intervals imposed between choices four and five. Administration of bicuculline immediately following the first four choices produced an impairment in maze performance at both a 1- and a 4-h delay interval. This treatment also produced an increase in latency per choice. Bicuculline-induced impairments were not observed when administered 2 h following the predelay session (2 h prior to testing). These data support previous observations that pharmacological manipulation of GABAergic activity within the septum modifies working memory processes.     

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.     

Does a cognitive map guide choices in the radial-arm maze?

Fifteen rats performed in a standard radial-arm maze task (Experiment 1) and in a modified task with a set of forced choices and a 15-min retention interval prior to completion of the maze (Experiment 2). In addition to the standard measure of choice in the radial-arm maze, orientation toward arms was measured and considered to constitute go-no-go "microchoice" decisions. Rats investigated but rejected many arms. A model of choice was developed in which it was assumed that choice decisions about arms were made independently and that microchoices were not selectively guided toward baited arms. The model performed nearly as well as the rats. These results place important limitations on the theory that choice behavior in the radial-arm maze is guided by a cognitive map.     

Differential effects of estrogen on hippocampal- and striatal-dependent learning

Estrogen's role in learning and memory may be to predispose animals to use specific cognitive strategies (Korol & Kolo, 2002). Specifically, estrogen may facilitate hippocampal-dependent learning, while at the same time attenuate striatal-dependent learning. As a stringent test of this hypothesis, place or response learning on an eight-arm radial maze was compared between ovariectomized (OVX) female Long-Evans rats and rats with chronic estrogen replacement (OVX+E; 5mg 17-beta estradiol 60-day release tablet). Reference and working memory errors were monitored separately for both place and response learning tasks. OVX+E rats learned the place task significantly faster than the response task, and faster than OVX rats. OVX rats required fewer days to reach criterion on the response task than OVX+E rats. Estrogen selectively enhanced reference memory performance, but only during place learning. The specific pattern of estrogen effects on learning suggests that future studies include verification of cognitive strategies used by animals.     

Stimulus control of spatial behavior on the eight-arm maze in rats

Rats were trained on an eight-arm, elevated radial maze in a large cylindrical chamber where extramaze stimuli could be manipulated. The first experiment indicated that rats could use extramaze stimuli to locate the arms if such stimuli were available, whereas they performed less effectively and tended to employ response chaining if these stimuli were not available. The second experiment demonstrated that maze performance was disrupted by transposition of the stimuli but was relatively unaffected by rotation of the same stimuli. The third experiment suggested that the disruptive effect of stimulus transposition might be due to a “resetting” process elicited by the alteration in the configuration of the stimuli after stimulus transposition. These results suggest that when extramaze stimuli are available, rats tend to use such stimuli in a configurational manner to locate the arms rather than as a list of items processed independently of their spatial relationships to each other.     

Effects of the nicotinic receptor blocker mecamylamine on radial-arm maze performance in rats

Lesions of cholinergic neurons have been found by many investigators to impair choice accuracy in the radial arm maze. Because muscarinic receptor blockers, such as scopolamine, have also repeatedly been found to impair choice accuracy in the radial-arm maze, it has generally been thought that the critical effect of cholinergic lesions is the deafferentation of muscarinic receptors. The possible involvement of nicotinic receptors in the cholinergic bases of cognitive performance in the radial-arm maze has not been as well investigated. The present study examined the effects of the blockade of nicotinic receptors on performance of female Sprague-Dawley rats in the radial-arm maze. Acute administration of the the nicotinic receptor blocker, mecamylamine (10 mg/kg) was found to significantly impair radial-arm maze choice accuracy. This dose also caused a significant increase in response latency in the maze. The effect on choice behavior but not locomotor speed seemed to be due to the central effects of mecamylamine, because administration of the peripheral nicotine receptor blocker, hexamethonium (20 mg/kg), did not impair choice accuracy, even though it did increase response latency to a similar degree as the 10-mg/kg dose of mecamylamine. Lower doses of mecamylamine (2.5 and 5 mg/kg) did not impair choice accuracy. These results indicate that central nicotinic as well as muscarinic cholinergic receptors are involved with cognitive functioning.     

Does the radial arm maze necessarily test spatial memory?

Since its design 25 years ago (Olton & Samuelson, 1976), the eight-arm radial maze has become very popular and is now widely used to assess spatial memory in rodents. Two versions of the full-baited maze protocol are present in the literature: with or without confinement between the visit of each arm. The confinement was introduced by Olton himself as early as 1977 (Olton, Collison, & Werz, 1977) to eliminate stereotypic behaviors that he had previously observed. It is widely regarded that the confinement prevents rodents from developing these response patterns, and as such it is considered an improved procedure to test spatial memory. Surprisingly, to the best of our knowledge, no study has been especially designed to demonstrate the efficacy of the confinement in blocking the stereotypic behaviors of the animals. The present study compares the strategies of rats trained with or without a confinement procedure. The results show that, after nine days of training, rats submitted to a 5- or a 10-s confinement reach the same level of performance as rats without confinement. The confinement totally prevents stereotypic behaviors like clockwise serial searching strategies which are often observed without confinement. Even a 0-s confinement is sufficient to prevent clockwise strategies, but rats seem to develop other stratagems which do not imply spatial memory. Furthermore, rats previously trained without confinement are unable to perform the task when confinement is introduced on a test day. In contrast, rats previously trained with confinement perform the task correctly when the confinement is no longer present. Thus, without confinement, good levels of performance can be achieved without precise spatial representations.     

Evidence for neocortical involvement in reference memory

Rats were trained on an eight-arm radial maze task using a procedure that provides for an assessment of both working and reference memory. Following training, rats received parietal cortex, medial prefrontal cortex, visual cortex, or nucleus basalis magnocellularis lesions. Rats with visual cortex lesions showed no change in performance on either working or reference memory. Rats with parietal cortex lesions displayed a temporary deficit in reference, but no deficit on working memory. Animals with medial prefrontal cortex lesions showed a temporary deficit on both working and reference memory. Rats with extensive lateral frontal and parietal cortex depletion of acetylcholinesterase following nucleus basalis magnocellularis lesions had a marked disruption only of reference but not of working memory. It is concluded that neocortex and possibly the cholinergic projections to neocortex play an important role in mediating reference memory.     

Serial position curves in rats: automatic versus effortful information processing

Rats were trained to remember lists of five arms on an Olton eight-arm radial maze. A forced-choice memory recognition test procedure was used which required the animal to choose between an arm previously visited during the study phase of a trial and an arm not visited. To receive additional food reinforcement, 10 animals were required to return to the previously visited arm (win-stay) and 10 animals were required to choose the novel, unvisited arm (win-shift). In this way, a direct comparison was made between the serial position curves (SPCs) generated by win-stay trained and win-shift trained animals. The results indicated that only win-stay trained animals produced the classical U-shaped SPC, which included significant primacy and recency effects. Win-shift subjects showed only recency effects. These findings are discussed in terms of differential processing requirements for the two procedures. It is suggested that the win-stay rule necessitates relatively more effortful, elaborative processing than does the win-shift rule, which is used automatically.     

Lesions of the rat postsubiculum impair performance on spatial tasks.

Previous studies have identified a population of neurons in the postsubiculum that discharge as a function of the rat's head direction in the horizontal plane (Taube, Muller, & Ranck, 1990a). To assess the contribution of these cells in spatial learning, Long-Evans rats were tested in a variety of spatial and nonspatial tasks following bilateral electrolytic or neurotoxic lesions of the postsubiculum. Compared to unlesioned control animals, lesioned animals were impaired on two spatial tasks, a radial eight-arm maze task and a Morris water task, although the performance scores of both lesion groups improved over the course of behavioral testing. In contrast, lesioned animals were unimpaired on two nonspatial tasks, a cued version of the water maze task and a conditioned taste-aversion paradigm. In addition, lesioned animals showed transient hyperactivity in an open-field activity test. These results support the concept that neurons in the postsubiculum are part of a neural network involved in the processing of spatial information.     

Neural and behavioural effects of domoic acid, an amnesic shellfish toxin, in the rat.

To examine the neurotoxic effects of domoic acid, an amnesic shellfish toxin, electroencephalographic and behavioural experiments were conducted on 38 rats. Injection of domoic acid (0.5-1.0 mg/kg intravenously, or 0.04-0.08 microgram intraventricularly) caused seizure discharges in the hippocampus, tonic-clonic convulsions, and death within a few days. Convulsions and ensuing death were prevented by diazepam. Animals pretreated with diazepam (5 mg/kg, ip) tolerated intraventricular dose of domoic acid 0.4 microgram, but showed a loss of pyramidal neurons mainly in the CA3, CA4, and a part of CA1 areas of the dorsal hippocampus. Learning of a radial maze task was severely impaired in naive rats after intraventricular injection of domoic acid (and diazepam, ip). In the animals previously trained on the maze task, domoic acid interfered with relearning of the same task. These effects appear similar to those of kainic acid and are analogous to the symptoms observed in humans who ingested mussels tainted with domoic acid.     

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.