Environmental cue saliency influences the vividness of a remote spatial memory in rats

The Morris water maze is frequently used to evaluate the acquisition and retrieval of spatial memories. Few experiments, however, have investigated the effects of environmental cue saliency on the strength or persistence of such memories after a short vs. long post-acquisition interval. Using a Morris water maze, we therefore tested in rats the effect of the saliency of distal cues on the vividness of a recent (5 days) vs. remote (25 days) memory. Rats trained in a cue-enriched vs. a cue-impoverished context showed a better overall level of performance during acquisition. Furthermore, the probe trials revealed that the rats trained and tested in the cue-impoverished context (1) spent less time in the target quadrant at the 25-day delay, and (2) swam shorter distances in the target area, with fewer crossings at both 5- and 25-day delays, as compared to their counterparts trained and tested in the cue-enriched context. Thus, the memory trace formed in the cue-enriched context shows better resistance to time, suggesting an implication of cue saliency in the vividness of a spatial memory.     

Chronic propranolol induces deficits in retention but not acquisition performance in the water maze in mice

Agents that alter adrenergic receptors, such as "beta-blockers," also alter memory storage. However, reports suggest that beta-adrenergic receptor antagonists, such as propranolol, have conflicting behavioral effects with acute vs chronic dosing. This study was designed to evaluate the effects of chronic propranolol on retention for a spatial learning task. Adult male ICR mice were given daily injections of propranolol (2, 4, 8, or 12 mg/kg ip) or 0. 9% NaCl for 15 days prior to, and during, trials in a Morris water maze. Mice received five massed acquisition (escape) trials in each of three daily sessions, followed by a single 60-s probe trial on the fourth day. The location of the submerged platform was constant for each animal over acquisition trials, but varied across animals; starting position varied across trials. A 5 (dose) x 3 (trial blocks) mixed factorial ANOVA for escape time yielded a significant trial blocks effect only (p <.001), showing performance improving over sessions. Time spent in the target quadrant on the probe trial was shorter under all doses of propranolol when compared to vehicle group (all p <.001), indicating poorer retention of prior platform location. This effect, however, was not dose-related. Swim speed was not significantly affected by propranolol. These data demonstrate that chronic dosing with propranolol can impair retention of spatial learning, which cannot be attributed to reduced arousal or motor function.     

Extinction of appetitive learning is disrupted by cycloheximide and propranolol in the sand maze in rats

The present study investigated whether memory for extinction in an appetitive task (the sand maze) could be attenuated by administration of cycloheximide (protein synthesis inhibitor) or propranolol (β-adrenergic receptor antagonist). Ninety-day-old male Long-Evans rats were trained to retrieve a sweet cereal reinforcer from an open container in the sand maze. One day following this non-spatial training, rats received three extinction trials in which they were placed in the maze with the reinforcer present, but unattainable. Thirty minutes prior to the first extinction trial, rats received an intraperitoneal injection of cycloheximide (1mg/kg), propranolol (25mg/kg), or vehicle (1mg/kg distilled water). Twenty-four hours later, rats were tested in the sand maze with the reinforcer again available. Results from the test trial showed that both cycloheximide and propranolol groups found the reinforcer more quickly than controls. Two weeks later, rats were trained on a spatial version of the sand maze in which they had to search for a buried reinforcer using extramaze cues. Cycloheximide and propranolol groups learned this task significantly faster than the control group, demonstrating the long-lasting effect of cycloheximide and propranolol on the blocking of memory for extinction.     

Post-training administration of corticotropin-releasing hormone (CRH) enhances retention of a spatial memory through a noradrenergic mechanism in male rats

Hormones released in response to stress play important roles in cognition. In the present study, the effects of the stress peptide, corticotropin-releasing hormone (CRH), on spatial reference memory were assessed following post-training administration. Adult Long-Evans male rats were trained for 6 days on a standard water maze task of reference memory in which animals must learn and remember the fixed location of a hidden, submerged platform. Each day, immediately following three training trials, rats received bilateral infusions of CRH into the lateral ventricles over a range of doses (0.1, 0.33, 1.0, 3.3 μg) or a vehicle solution. Post-training infusions of CRH improved retention as indicated by significantly shorter latencies and path lengths to locate the hidden platform on the first training (retention) trial of days 2 and 3. Additionally, post-training administration of CRH increased spatial bias during probe trials as measured by proximity to the platform location. CRH did not enhance performance on retention or probe trials when administered 2 h after daily training indicating that CRH facilitated consolidation specifically. The effects of CRH were attenuated by intraventricular co-administration of the beta-adrenergic antagonist, propanolol, at bilateral doses that had no effect on retention alone (0.1, 1.0 μg). Results indicate that post-training administration of CRH enhanced spatial memory as measured in a water maze, and this effect was mediated, at least partly, by a noradrenergic mechanism.     

Recent exposure to a dangerous context impairs extinction and reinstates lost fear reactions

Rats were shocked in a context and then exposed to that context in the absence of shock. Shorter intervals between these extinction trials produced more long-term freezing than did longer ones, and shorter intervals between the final extinction trial and test produced more freezing than did longer ones. A short interval between a context extinction trial and test with an extinguished conditioned stimulus (CS) produced more freezing than did a longer one, and a short interval between a nonreinforced context exposure and an extinguished CS reinstated freezing when the CS was tested 24 hr later. The results suggest that recent fear acts to favor subsequent retrieval of the memory formed at conditioning rather than extinction and to render the retrieved memory more salient.     

Spatial Memory and Response Strategies in Rats: Age, Sex and Rearing Differences in Performance

Rats reared in social isolation made more errors on a spatial memory task and made errors earlier in each trial than socially reared rats. The difference in performance only occurred when rats were isolated prior to 50 days of age, and it survived IOO days of subsequent social housing. IOO days of isolation after 50 days of age did not influence performance on the spatial memory task. Subsequent experiments suggest that spatial abilities may not differ between groups but that isolates are slower to learn to make a particular response and to locate a particular arm when spatial and response cues are irrelevant. In contrast to previous experiments, clear response strategies were seen in the present experiments. These were prevalent in the young (54-days-old) rats, were less common at 90 days and had completely disappeared by 180 days. Response strategies were more common in male rats and in socially reared rats.     

Development of place navigation in rats from weaning to puberty

Young hooded rats were trained to escape onto a hidden platform after swimming in a pool of opaque water. Subjects 21, 28, 35, 42, and 64 days of age on the first training day were given 28 trials on 5 consecutive days. Half of the rats were required to localize the platform in relation to external room cues only ("place only" condition) and the other half were helped by the presence of a visible cue on the platform ("cue + place" condition). A deficiency in place navigation was observed in the 21- and 28-day groups; they showed slow escape and took circuitous routes more often than older rats. This deficiency was related to a poor spatial bias toward the training position when the subjects were allowed to swim for 30 s in the absence of the platform, at the end of the 28-trial training period (probe trial). The 35-day group showed adult-like learning ability in both training conditions, but failed to show searching behavior during the probe trial after having been trained in the presence of the proximal cue. Only rats older than 40 days showed typical adult behavior such as swimming directly toward the platform from any starting position and localized searching around the absent platform's position during the probe trial, no matter what the training conditions were. These results suggest that central nervous system structures responsible for place learning in the rat are functional from around 32 days of age, but fail to trigger searching behavior following cued training before the sixth week.     

东莨菪碱对大鼠空间参考记忆和工作记忆的不同影响

观察东莨菪碱对空间参考记忆和空间工作记忆的编码、保持和提取过程的作用。应用Morris水迷宫实验测定大鼠的空间参考记忆和空间工作记忆,分别在训练的不同阶段腹腔注射东莨菪碱（1mg/kg）和相同容量的生理盐水,比较各东莨菪碱组和生理盐水组之间游泳潜伏期、路径长度、轨迹和游泳速度的差异。结果发现：与注射生理盐水相比,在训练前和探测实验前注射东莨菪碱的大鼠在探测实验中对目标象限不表现出空间偏爱,说明东莨菪碱干扰参考记忆的信息编码和提取过程;而在训练结束后注射东莨菪碱的大鼠探测实验的结果与生理盐水组相比没有显著差异,说明东莨菪碱对参考记忆的保持过程没有影响。在工作记忆实验中,无论第一次测试前、第一次测试后和第2次测试前注射东莨菪碱,均造成大鼠游泳潜伏期延长,说明东莨菪碱干扰工作记忆的编码、保持和提取过程。研究提示M受体在空间工作记忆和参考记忆中发挥不同作用     

One retrieval trial induces reconsolidation in an appetitive learning paradigm in honeybees (Apis mellifera)

Combining memory retrieval with the application of a protein synthesis-inhibitor leads to an amnestic effect that is referred to as the reconsolidation phenomenon. Several behavioural studies demonstrate that only a few or weak retrieval trials (that do not result in significant extinction) lead to this phenomenon. In contrast, many trials (that result in significant extinction) combined with a protein synthesis inhibitor result in an inhibition of the extinction memory. Based on these findings it was suggested that extinction is the boundary condition for reconsolidation: when extinction is induced the consolidation of the extinction memory is the dominant process. Recently we were not able to confirm this hypothesis in the honeybee (Apis mellifera): We did not find the reconsolidation phenomenon after one retrieval trial, but demonstrated reconsolidation after five retrieval trials that led to extinction. To exclude that this observation resembles a special case in insects we here wanted to know if one retrieval trial induces reconsolidation as it has been demonstrated before in many other species. To do so we used experimental parameters that had been used before to demonstrate consolidation in the honeybee with the exception that this time the protein synthesis-inhibitor was applied 1 h after one memory retrieval instead after acquisition. We thereby demonstrate the reconsolidation phenomenon after one retrieval trial but only when using the doubled dose of protein synthesis-inhibitor that has been used to inhibit consolidation.     

Protective effect of practice on cognition during aging: implications for predictive characteristics of performance and efficacy of practice

In the present study, the effect of previous experience on spatial memory, which required the retention of information either over long intervals or within a single session, was longitudinally tested in the water maze in male F-344 rats that were from 6 to 24 months of age. Performance in these tasks was found to be age-dependent (Markowska, 1999). Other behavioral tasks in the straight alley and with a visible platform in the water maze controlled the noncognitive components of performance. For all tasks, performance was significantly correlated between 12-month-old and 18-month-old rats, indicating that cognitive performance at the early, but not advanced, stage of aging could be predicted from performance at a younger age if the novelty of the first exposure to the task was eliminated. The protective effect of experience was more robust in the reference memory task as compared to the working memory task and was modified by age when training was initiated. Behavior during the probe trials was more sensitive to the effect of aging and more resistant to the beneficial effect of practice as compared to the performance in the platform trials. The speed of swimming of experienced rats progressively decreased with age only when tested in the cognitive tasks but not in the straight alley. This indicates that speed of swimming during cognitive tasks does not exclusively reflect the ability to swim, but might be also affected by the cognitive demands of the task. Protective effect of experience on cognition was not modified by restriction in diet.     

Partial reinforcement and partial delay of reinforcement effects with 72-hour intertrial intervals and interpolated continuous reinforcement

Three groups of rats ran 108 trials in a straight runway, one trial every 3 days. On the first 44 trials, one group received continuous (and immediate) reinforcement (CRF), a second group 50 per cent partial reinforcement (PRF), and the third group a 50 per cent schedule of partial delay of reinforcement (PDR). All groups received CRF on the next 20 trials, and extinction on the last 44 trials. The PRF and PDR groups extinguished at approximately the same rate, and significantly more slowly than the CRF group.     

Higher levels of estradiol replacement correlate with better spatial memory in surgically menopausal young and middle-aged rats

The current study investigated whether, for spatial reference memory, age impacts (1) sensitivity to surgical ovarian hormone loss (Ovx), (2) response to estradiol therapy (ET), and (3) the relation between circulating estradiol levels and memory scores in ovary-intact sham and Ovx plus ET rats. Young, middle-aged and aged Fischer-344 rats received sham, Ovx or Ovx plus ET treatments, and were then tested on the Morris maze. After the last test trial, a probe trial was given whereby the platform was removed. Circulating estradiol levels were then determined and correlated with performance. In Study 1, Ovx facilitated learning on day one, but impaired performance after day one, in young rats. Ovx did not influence performance in middle-aged rats. In young and middle-aged Ovx rats, ET enhanced performance with higher exogenous estradiol levels correlating with better performance during testing and the probe trial. There was no relationship between endogenous estradiol levels and performance in sham young or middle-aged rats. Study 2 showed that, like middle-aged rats, aged rats were not impacted by Ovx. Further, for aged Ovx rats, the ET regimen that was beneficial at earlier ages was no longer effective during test trials, and had only minor benefits for platform localization as assessed by the probe trial. Collectively, the findings suggest that the effects of Ovx as well as responsivity to the currently utilized ET regimen changes with age. Further, there appears to be a distinction between sensitivity to Ovx and responsiveness to ET after Ovx for spatial reference memory performance.     

The canine sand maze: an appetitive spatial memory paradigm sensitive to age-related change in dogs

Aged dogs exhibit a spectrum of cognitive abilities including a syndrome similar to Alzheimer's disease. A major impediment to research so far has been the lack of a quick and accurate test of visuospatial memory appropriate for community-based animals. We therefore report on the development and validation of the Canine Sand Maze. A 4.5-m-diameter circular pool was filled with a sand and powdered food reward mix to a depth of 10 cm. Dogs were given 4 habituation and 16 learning trials which alternated a food reward being half (control trials) or fully-buried (acquisition trials) in a fixed location. After a 90-min break, a probe trial was conducted. Cognitively normal, aged (> 8 years, n = 11) and young (1-4 years, n = 11), breed-matched dogs were compared. After correction for differences in control trials, average probe times were 2.97 and 10.81 s for young and aged dogs, respectively. In the probe trial, both groups spent significantly more time in the target quadrant but there was a trend for young dogs to cross a 1 m(2) annulus zone around the buried reward more frequently (2.6 times) than aged dogs (1.5 times). Test-retest reliability in a subset of young dogs (n = 5) was high. On the basis of these findings, the Canine Sand Maze is presented as a quick, sensitive and nonaversive tool for assessing spatial learning and reference memory in dogs.     

MK-801 improves retention in aged rats: implications for altered neural plasticity in age-related memory deficits

Alterations in N-methyl-d-aspartate receptor (NMDAR)-dependent synaptic plasticity, characteristic of aged rodents, may contribute to impaired memory with advanced age. The purpose of the current research was to examine whether NMDARs contribute to rapid forgetting on a spatial memory task. Aged (22-24 months) and adult (3-6 months) male Fischer 344 rats received 18 training trials, over a period of 3 to 4 h, on the spatial version of the Morris water maze. Immediately after training, a standard free-swim probe trial was administered to assess the acquisition of spatial bias, which was determined by the percent of time spent in the goal quadrant and the number of platform crossings. Rats then received injections of the noncompetitive NMDAR antagonist, (+)-10, 11-dihydro-5methyl-5H-dibenzo(a,b)cycloheptene-5,10 imine (MK-801, 0. 05 mg/kg, i.p.), or a vehicle injection of equal volume. Approximately 24 h later, rats were administered a second free-swim probe trial to assess retention of spatial bias. All age/drug groups exhibited a spatial bias on the acquisition probe, with adults generally outperforming the aged rats. On the retention probe, this spatial bias continued to be shown by adult rats, regardless of treatment. For the aged group, in contrast, only MK-801-injected rats maintained a spatial bias on the retention probe, suggesting that NMDAR activity may be involved in rapid forgetting during aging. Because blockade of NMDARs also may impair new learning, which may, in turn, protect previously stored information from retroactive interference, rats in a second experiment received post-training injections of scopolamine (0.05 mg/kg), a compound known to inhibit learning. However, scopolamine did not enhance retention in the aged group, consistent with the hypothesis that MK-801 influenced memory in aged rats through its actions on NMDAR-dependent synaptic plasticity.     

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.     

Grouping, chunking, memory, and learning

An example of grouping is dividing a long series of digits into two or more smaller units by, for example, pausing for a short time between items within groups but for a longer time between groups. Grouping, virtually neglected in animal learning, was examined in each of five rat investigations reported here in which a series of two or more runway trials was either grouped together with or apart from a terminal large reward trial. It was found that running speed on early small reward trials in the series was greater when prior trials were grouped together with rather than apart from the terminal large reward trial and this when the intertrial interval was short, 20 sec, or long, 20 to 40 min. Three possible explanations of the present findings were examined: a reward schedule view, a rule-learning view, and an anticipation view based on memory. The most feasible of these explanations, it was suggested, was the anticipation view. According to this view, when prior trials are grouped together with a terminal large reward, there is a tendency for the rat to anticipate the terminal large reward well before its scheduled occurrence, elevating running speed on earlier small reward trials. Such anticipation occurs, it was suggested, because when trials are grouped together the memory of each reward event in the series is retrieved on each subsequent trial, including the remote terminal large reward trial, where it becomes a signal for large reward. Thus the present results implicate not merely adjacent associations—associations between adjacent events—but also the highly controversial remote associations—associations between two events separated not only in time but by one or more intervening events as well.     

Primacy, recency, and suffix effects in auditory short-term memory for pure tones: evidence from a probe recognition paradigm.

The present study was designed to explore serial position and suffix effects in the short-term retention of nonverbal sounds. In contrast with previous studies of these effects, a probe recognition paradigm was used to minimize the possibility that participants would use a verbal labelling strategy. On each trial, participants heard a memory set consisting of three pure tones, followed five seconds later by a probe tone. Participants were required to indicate whether or not the probe tone had been a member of the memory set. On most trials, a suffix sound was presented 1 second following the third sound in the memory set. Results revealed that tones presented in the first and last positions of the memory set were recognized more accurately than were tones presented in the middle position. Furthermore, recognition of sounds presented in the last position was compromised when the memory set was followed by a postlist suffix of similar pitch, spectral composition, and spatial location.     

Conditional forebrain deletion of the L-type calcium channel Ca V 1.2 disrupts remote spatial memories in mice

To determine whether L-type voltage-gated calcium channels (L-VGCCs) are required for remote memory consolidation, we generated conditional knockout mice in which the L-VGCC isoform Ca(V)1.2 was postnatally deleted in the hippocampus and cortex. In the Morris water maze, both Ca(V)1.2 conditional knockout mice (Ca(V)1.2(cKO)) and control littermates displayed a marked decrease in escape latencies and performed equally well on probe trials administered during training. In distinct contrast to their performance during training, Ca(V)1.2(cKO) mice exhibited significant impairments in spatial memory when examined 30 d after training, suggesting that Ca(V)1.2 plays a critical role in consolidation of remote spatial memories.     

Extinction memory in the crab Chasmagnathus: recovery protocols and effects of multi-trial extinction training

A decline in the frequency or intensity of a conditioned behavior following the withdrawal of the reinforcement is called experimental extinction. However, the experimental manipulation necessary to trigger memory reconsolidation or extinction is to expose the animal to the conditioned stimulus in the absence of reinforcement. Recovery protocols were used to reveal which of these two processes was developed. By using the crab contextual memory model (a visual danger stimulus associated with the training context), we investigated the dynamics of extinction memory in Chasmagnathus. Here, we reveal the presence of three recovery protocols that restore the original memory: the old memory comes back 4 days after the extinction training, or when a weak training is administered later, or once the VDS is presented in a novel context 24 h after the extinction session. Another objective was to evaluate whether the administration of multi-trial extinction training could trigger an extinction memory in Chasmagnathus. The results evince that the extinction memory appears only when the total re-exposure time is around 90 min independently of the number of trials employed to accumulate it. Thus, it is feasible that the mechanisms described for the case of the extinction memory acquired through a single training trial are valid for multi-trial extinction protocols. Finally, these results are in agreement with those reports obtained with models phylogenetically far apart from the crab. Behind this attempt is the idea that in the domain of studies on memory, some principles of behavior organization and basic mechanisms have universal validity.     

Spatial behavior in male and female crayfish (Orconectes rusticus): learning strategies and memory duration

Previous studies have demonstrated that animals use multiple strategies to solve spatial tasks. We used a T-maze to examine spatial behavior in crayfish, using visual and tactile stimuli as place cues and a food-scented escape tank as reinforcement to leave the maze. In trials on a single day and across multiple days, crayfish learned to exit the maze with significantly reduced latency and with fewer turns. In addition, we examined place memory in 40-min periods with the maze closed and found that crayfish spent longer in the vicinity of a previously open exit compared to a closed exit. Probe tests were conducted using a forced-choice procedure to determine whether crayfish remembered the route out of the maze using primarily place cues or response learning. We found that approximately equal numbers of animals used each strategy, and individuals were able to switch from one strategy to the other on different test days. Males and females did not differ significantly in their performance in the place memory test, maze exit task, or probe tests. Both sexes displayed place memory for the exit location and reduced latency to exit during trials 24 h, 48 h, 72 h, and 1 week after initial training trials, suggesting that spatial memories in crayfish are relatively enduring.