Estrogen replacement in ovariectomized rats affects strategy selection in the Morris water maze

While estrogen enhances performance on some tasks of learning and memory, it has impairing or no effects on others. It has been proposed that estrogen differentially affects performance on various tasks of learning and memory by influencing the strategy used to solve a task. The goal of the present study was to determine if estrogen would influence strategy selection in the Morris water maze. Long-Evans rats were ovariectomized and implanted with Silastic capsules containing 25% estradiol diluted in cholesterol or 100% cholesterol. Rats were trained in a water maze task in which multiple strategies were available for use to locate a hidden escape platform that was moved to a new location for each set of four daily trials. During 10 days of acquisition trials, a visible floating landmark was always located in a static position relative to the hidden escape platform. Additionally, fixed extramaze cues visible to the animals surrounded the maze. Following acquisition, 2 days of probe trials were conducted in which the static landmark was removed. Estrogen replacement in ovariectomized rats resulted in impaired performance across 10 days of acquisition. Additionally, while removal of the visible landmark during the probe trials had no effect on the performance of the females receiving estrogen, it significantly disrupted performance of females receiving cholesterol treatment. These results indicate that estrogen replacement in ovariectomized rats biases an animal against using a landmark or static cue to aid in the location of a hidden escape platform in the water maze.     

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.     

Differential Effects of Global Ischemia on Delayed Matching- and Non-Matching-to-Position Tasks in the Water Maze and Skinner Box

In order to assess effects of global ischemia in tasks of spatial learning and working memory, male Wistar rats were subjected to four vessel occlusion (4 VO) for periods of 5, 10, and 20 min and compared with sham-operated controls over four test phases, from 6 to 54 weeks after surgery. Rats were assessed on acquisition in the water maze, a task that is sensitive to ischemic impairments, before testing in Skinner box and water maze working memory tasks, which both require the short-term storage of information, but make different demands on spatial information processing. Phases 1 and 3 assessed spatial learning in a standard water maze procedure (12 and 10 training days, 2 trials/day with a 10-min intertrial interval: ITI). Phase 2 involved training and testing in delayed non-matching-to-position task in the Skinner box, with delays of 2–10 s between the information and choice stages. Phase 4 examined working memory in a water maze delayed matching-to-position task with 4 trials/day, an ITI of 30 s, and a novel platform position on each day. Ischemic rats showed duration-related impairments in water maze acquisition and working memory, but not in the less spatially demanding Skinner box task. Since water maze acquisition deficits were seen both before and after testing in the Skinner box the lack of effect cannot be attributed to time or to prior training. Ischemic deficits were more marked in Phase 3 than in Phase 1 of acquisition, suggesting that impairment may be progressive. Histological assessment showed that cell loss was largely confined to the hippocampal CA1 field and was linearly related to duration of occlusion. At the maximal level of loss (5.7 mm before the interaural line) the 20-min group showed 90% loss, the 10-min group 60% loss, and the 5-min group, which did not differ from controls, less than 10% loss. Only the 20-min group showed significant damage beyond the CA1 field, ranging from 30–40% loss in the CA3 field to 5% loss in one striatal area. No cortical damage was seen. The extent of CA1 cell loss correlated modestly with water maze acquisition (Phase 3) and working memory scores, but not with trials to criterion in the Skinner box task. There were significant correlations between different measures both within and between water maze tasks, but not Skinner box tasks, suggesting that the two types of procedure engaged different cognitive processes. The results indicate that the intrahippocampal damage induced by 4 VO impaired tasks which required processing of allocentric spatial information, but did not impair the storage of limited spatial information in working memory.     

The effects of aging and dorsal hippocampal lesions: performance on spatial and nonspatial comparable versions of the water maze

Aged intact and young hippocampal-lesioned rats show similar deficits on the spatial water maze. However, this does not necessitate that the source of these deficits in the aged animals is due to hippocampal damage. These water maze deficits may arise from other aging factors such as changes in thermoregulation, muscle fatigue, swim ability, and response to stress. Consequently, it is imperative to examine the performance of aged rats on a comparable nonhippocampal version of this task. Past attempts to develop a hippocampus-independent version of the water maze were confounded because these tasks were easier (i.e., the rats spent much less time swimming in the water) than the spatial versions of the task. The current study examined performance on a hippocampus-independent task comparable in difficulty to the spatial water one. Middle-aged (16-m) and old (25-m) male F344 rats were given sham or dorsal hippocampus lesions and tested on both a spatial and a nonspatial water maze. The middle-aged rats with hippocampal lesions were impaired on the spatial task but not on the nonspatial task. Conversely, aged animals showed a similar impairment on both types of water maze tasks. Additionally, hippocampal lesions exacerbated the age-related impairment on both tasks. These findings indicate that caution must be used when interpreting the results of water maze tasks for aged animals.     

Vitamins E and C pretreatment prevents ovariectomy-induced memory deficits in water maze

We investigated whether the pretreatment with vitamins E (alpha-tocopherol) and C (ascorbic acid) would act on ovariectomy-induced memory deficits in Morris water maze tasks. Adult female Wistar rats were divided into three groups: (1) naive (control), (2) sham (submitted to surgery without removal of ovaries) and (3) ovariectomized. Thirty days after surgery, they were trained in the Morris water maze in order to verify ovariectomy effects both on reference and working memory tasks. Results show that ovariectomized rats presented impairment in spatial navigation in the acquisition phase, as well as in the time spent in target quadrant and in the latency to cross over the location of the platform in test session, when compared to naive and sham groups (controls), in the reference memory task. Ovariectomy did not affect performance in the working memory task. Confirming our hypothesis, ovariectomized rats pretreated for 30 days with vitamins E and C had those impairments prevented. We conclude that ovariectomy significantly impairs spatial reference learning/memory and that pretreatment with vitamins E and C prevents such effect. Assuming this experimental memory impairment might mimic, at least in part, the cognitive deficit sometimes present in the human condition of lack of reproductive hormones, our findings lend support to a novel therapeutic strategy, based on vitamins E and C, to cognitive impairments in post-menopausal women.     

Preserved spatial memory in old rats survives 10 months without training

Aged rats with extensive prior training on the radial maze retain the capacity for accurate spatial working memory (WM) for at least 3 months without practice. To investigate the temporal limits of this influence of prior experience we compared the reacquisition of spatial WM by a group of experienced 21.5-month-old rats to the original acquisition by naive 3-month-old rats. The aged rats had received 225 radial maze tests between 3 and 11 months of age. Despite 10 months without practice the old rats rapidly reacquired critical performance. Their reacquisition was markedly superior to original learning by the young rats, even when delays as long as 5 h were imposed between the rats' fourth and fifth choices during the daily tests in the eight-arm maze. Additional tests showed that neither young nor old rats employed a response strategy to maintain accurate spatial WM performance. Experience clearly confers long-lived protection against the otherwise deleterious effects of aging on spatial WM, but the mechanism by which this influence arises is unknown.     

Latent learning in a swimming pool place task by rats: Evidence for the use of associative and not cognitive mapping processes

Using a latent learning paradigm, the experiments examine two hypotheses of how rats solve place navigation tasks. According to associative theory, experience with all relevant cues is required for accurate navigation. According to cognitive mapping theory, animals can generate novel trajectories from knowledge of spatial relations of objects in the environment. Rats that had been placed on a platform, which was submerged in a pool of opaque water and was moved each day, were tested later for their ability to find the platform using only surrounding room cues. One 30-sec exposure to a platform location was effective in improving performance. Improvement was greatest when tests were given within minutes of placement, but facilitation was obtained for as long as 4 hr. Improved performance was obtained as soon as rats acquired the procedural aspects of the task but did not increase with subsequent practice. Improved performance was also obtained when pre-trained rats were tested in a novel environment. Despite the advantage conferred by exposure to the target platform, test swims were not accurate, placement-induced improvement was not as great as that following a single swimming trial, and placement combined with a swim resulted in best performance. The results suggest that rats use associative learning processes rather than cognitive mapping to solve place problems in a swimming pool.     

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.     

Bidirectional interactions between circadian entrainment and cognitive performance

Circadian rhythms influence a variety of physiological and behavioral processes; however, little is known about how circadian rhythms interact with the organisms' ability to acquire and retain information about their environment. These experiments tested whether rats trained outside their endogenous active period demonstrate the same rate of acquisition, daily performance, and remote memory ability as their nocturnally trained counterparts in tasks of sustained attention and spatial memory. Furthermore, we explored how daily task training influenced circadian patterns of activity. We found that rats demonstrate better acquisition and performance on an operant task requiring attentional effort when trained during the dark-phase. Time of day did not affect acquisition or performance on the Morris water maze; however, when animals were retested 2 wk after their last day of training, they showed better remote memory if training originally occurred during the dark-phase. Finally, attentional, but not spatial, task performance during the light-phase promotes a shift toward diurnality and the synchronization of activity to the time of daily training; this shift was most robust when the demands on the cognitive control of attention were highest. Our findings support a theory of bidirectional interactions between cognitive performance and circadian processes and are consistent with the view that the circadian abnormalities associated with shift-work, aging, and neuropsychiatric illnesses may contribute to the deleterious effects on cognition often present in these populations. Furthermore, these findings suggest that time of day should be an important consideration for a variety of cognitive tasks principally used in psychological and neuroscience research.     

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.     

Effect of chronic angiotensin converting enzyme inhibition on spatial memory and anxiety-like behaviours in rats

Angiotensin converting enzyme inhibitors (ACEis) are widely used anti-hypertensive agents that are also reported to have positive effects on mood and cognition. The present study examined the influence of the ACEi, perindopril, on cognitive performance and anxiety measures in rats. Two groups of rats were treated orally for one week with the ACEi, perindopril, at doses of 0.1 and 1.0mg/kg/day. Learning was assessed by the reference memory task in the water maze, comparing treated to control rats. Over five training days both perindopril-treated groups learnt the location of the submerged platform in the water maze task significantly faster than control rats. A 60s probe trial on day 6 showed that the 1.0mg/kg/day group spent significantly longer time in the training quadrant than control rats. This improved performance in the swim maze task was not due to the effect of perindopril on motor activity or the anxiety levels of the rats as perindopril-treated and control animals behaved similarly in activity boxes and on the elevated+maze. These results confirm the anecdotal human studies that ACEis have a positive influence on cognition and provide possibilities for ACEis to be developed into therapies for memory loss.     

Spatial memory in the rat on a hierarchical maze

Rats were trained and tested on a hierarchical radial maze, which consisted of eight primary alleys radiating from a central platform and three secondary alleys which branched off the end of each primary alley. In four experiments, rats in groups 1, 2, and 3 were tested on maze configurations consisting of one, two, or three secondary alleys, respectively, at the end of each primary alley. In Experiment 1, each group was trained to collect food pellets in the secondary alleys. By the end of training, rats in each group collected all pellets efficiently, with little repetition of entrances into either primary or secondary alleys. In Experiments 2 and 3, tests were carried out which required retention of entrances into secondary alleys, as well as primary alleys. Two trials were run in succession, with selected secondary alleys blocked on trial 1 but open and baited with food on trial 2. Animals in groups 2 and 3 showed very accurate retention of blocked secondary alleys, regardless of variation in pattern and number of alleys blocked. A fourth experiment controlled for the possible use of food cues in Experiments 2 and 3 by rebaiting all secondary alleys between trials 1 and 2. Subjects continued to choose previously blocked alleys on trial 2, thus demonstrating that choice of blocked alleys was based on memory and not on a tendency to approach visual or olfactory food cues. Several findings of these experiments suggest that memories for primary and secondary alley choices are encoded and stored within separate memory systems. Possible coding mechanisms for these systems are discussed with reference to a process of cognitive mapping.     

Dietary restriction inhibits spatial learning ability and hippocampal cell proliferation in rats1

Abstract: We investigated the effect of dietary restriction on spatial learning ability and hippocampal cell proliferation in adult rats using two spatial learning tasks and immunohistochemical staining with 5‐bromo‐2′‐deoxyuridine (BrdU). Sixteen rats were divided into restricted or ad lib feeding groups at 70 days of age, and were trained in the delayed‐matching‐to‐place (DMTP) task (a working memory task) from 93 days of age, and then the Morris water maze task (a reference memory task). Dietary restriction had no effect on the DMTP task with 30 s delay and on the water maze task. However, in the DMTP task with 30 min delay, restricted rats performed significantly more poorly than ad lib rats. Quantitative analysis of hippocampal cell proliferation revealed that the density of newborn cells in restricted rats was significantly lower than that in ad lib rats. These results suggest that a loss of proliferating capacity in the hippocampus may be a candidate for an anatomical and biological basis for the cognitive decline caused by dietary restriction.     

The Effects of Intra-amygdala Infusion of the AMPA Receptor Antagonist CNQX on Retention Performance Following Aversive Training

The aim of these experiments was to determine whether impaired retention performance in aversively motivated tasks, induced by blockade of amygdala AMPA receptors, is due to influences on mechanisms underlying memory retrieval or to other influences on performance. Rats received either footshock escape training (1 or 10 trials), or no foot shock, in a two-compartment straight alley and bilateral intra-amygdala infusions of the AMPA receptor antagonist CNQX (0.5 μg) were subsequently administered prior to inhibitory avoidance retention testing 8 days later. The CNQX impaired, but did not block, inhibitory avoidance retention performance as indicated by the initial latencies to enter the shock compartment. The animals were then retained in the alley until they remained in the starting compartment for 100 consecutive s and entries into the shock compartment were recorded as errors. In both the controls and CNQX-treated groups, increases in amount of original training resulted in fewer errors, indicating memory for the escape training. Furthermore, regardless of the amount of original training (i.e., 0, 1, or 10 trials), CNQX-treated groups made more errors. Other experiments examined intra-amygdala CNQX effects on reactivity to footshock, locomotor activity, and anxiety. CNQX decreased reactivity to footshock, blocked shock-induced decreases in locomotor activity, and had an anxiolytic effect in an elevated plus maze comparable to that induced by midazolam (0.5 μg). These findings suggest that intra-amygdala infusions of CNQX prior to retention testing affect inhibitory avoidance retention performance following aversive training by altering locomotor activity, reducing sensitivity to footshock, and reducing anxiety. The implications of these findings for hypotheses concerning amygdala function in aversively motivated learning and memory is discussed.     

Differential sensitivity of recent vs. remote memory traces to extinction in a water-maze task in rats

Extinction has mostly been studied in conditioning paradigms, more sparsely in spatial tasks, and never as a function of the age of a spatial memory. Using rats, we compared the time-course of extinction of a recent (5 days) vs. remote (25 days) spatial memory in a water maze, over three probe trials. When the trials were set 24h apart, performance in the remote memory group was significantly worse on the first probe trial and significantly better on the third probe trial, as compared to the recent memory group, thereby showing differences between cognitive operations underlying recent vs. remote memory extinction. In contrast, when trials were given consecutively, both groups showed a similar profile of extinction. Furthermore, in a room with overly-salient cues providing a strong remote memory trace, no difference between groups was observed when the spaced extinction paradigm was used. These results might be related to a balance between reconsolidation and extinction processes occurring after a first retrieval experience, of which the outcome may depend on the extinction protocol, and on the age and strength of a memory.     

Age benefits in everyday prospective memory: the influence of personal task importance, use of reminders and everyday stress

The present diary study examined everyday prospective memory tasks in younger and old adults and explored the role of personal task importance, use of reminders and everyday stress as possible correlates of age-related prospective memory performance in everyday life. Results revealed an age benefit in everyday prospective memory tasks. In addition, task importance was identified as a critical moderator of age-related prospective memory performance. More frequent use of reminders and lower levels of stress, however, were associated with better prospective memory performance in general but did not contribute to age-related prospective memory performance. Exploring further possible correlates of prospective memory revealed that the strategy to reprioritize initially planned intentions was associated with age benefits in everyday prospective memory. Results suggest that the age-related benefit observed in experimenter-given tasks transfers to everyday prospective memory and varies in dependence of motivational and cognitive factors. Implications for theoretical models of prospective memory and aging are discussed.     

Involvement of the posteroventral caudate-putamen in memory consolidation in the Morris water maze

Male Sprague-Dawley rats implanted with bilateral intracerebral guide cannulae were trained in the standard hidden platform version of the Morris water maze and given immediate posttraining infusions of the D2 dopamine receptor antagonist sulpiride (10.0 or 100.0 ng/side) or saline vehicle into the posteroventral caudate-putamen. Retention was tested 2 days later with a probe trial. Sulpiride-treated rats spent less time swimming near the trained platform location and more time in the periphery of the maze than controls, although their latency to reach the trained platform location was not significantly affected. The pattern of results suggests that whereas the posteroventral caudate-putamen seems to be involved in consolidation of memory in the Morris water maze, it may be involved in memory for procedural aspects of the task in a manner distinct from that of other brain regions such as the hippocampus.     

Time-based and event-based prospective memory across adulthood: underlying mechanisms and differential costs on the ongoing task

The authors investigated the phenomenon that performance in an ongoing task declines when individuals must carry out a prospective memory (PM) task. This effect is referred to as the PM interference effect. The authors examined whether the PM interference effect differs between event-based and time-based PM tasks and whether it is increased among the elderly. The authors also investigated adult age differences in PM performance and the potential underlying mechanisms of the age deficits in PM. They found that the PM interference effect was greater in event-based than in time-based tasks. However, aging was not associated with an increase in PM interference effects. Age differences in PM performance were more exaggerated in time-based than event-based PM, but they were not mediated by age differences in traditional cognitive ability measures. In time-based PM, age showed a unique adverse effect even after controlling for the ability to externally monitor the time, leading to the possibility that aging disrupts time-based PM because of deficits in internally processing the time.     

Effects of ketamine on tunnel maze and water maze performance in the rat

The NMDA receptor, which has been implicated in memory formation, is noncompetitively blocked by ketamine. The present study examines the effect of ketamine (0, 3, 6, 12, and 25 mg/kg body wt; ip) on tunnel maze and water maze performance in Wistar rats. In the hexagonal tunnel maze (HTM) high doses of ketamine (12 and 25 mg/kg) decreased locomotor activity. Moreover, ketamine induced perimeter walking (6, 12, and 25 mg/kg) and attenuated exploratory efficiency (25 mg/kg). When the HTM was converted into a modified six-arm radial maze, ketamine impaired short-term but not long-term memory. In the Morris water maze, rats injected with ketamine (12 and 25 mg/kg) acquired a spatial navigation task more slowly than controls. When the escape platform was removed, the drug-treated rats did not preferentially search for it in the area where the platform had been during the acquisition phase. However, when the escape platform was visible, no differences in the performance of ketamine-treated and control rats could be found. In summary, ketamine seems to attenuate some but not all forms of learning in the tunnel maze and it impairs the acquisition of a spatial navigation task.     

The Duration and Intensity of the Exposure Light as Factors in Determining the Course of the Subsequent Dark-Adaptation: I. the Matching Method

The authors investigated the phenomenon that performance in an ongoing task declines when individuals must carry out a prospective memory (PM) task. This effect is referred to as the PM interference effect. The authors examined whether the PM interference effect differs between event-based and time-based PM tasks and whether it is increased among the elderly. The authors also investigated adult age differences in PM performance and the potential underlying mechanisms of the age deficits in PM. They found that the PM interference effect was greater in event-based than in time-based tasks. However, aging was not associated with an increase in PM interference effects. Age differences in PM performance were more exaggerated in time-based than event-based PM, but they were not mediated by age differences in traditional cognitive ability measures. In time-based PM, age showed a unique adverse effect even after controlling for the ability to externally monitor the time, leading to the possibility that aging disrupts time-based PM because of deficits in internally processing the time.