Spatial learning and memory at defined points of the estrous cycle: Effects on performance of a hippocampal-dependent task.

Learning based on hippocampal-dependent spatial navigation in female rats was assessed at identified points in the estrous cycle corresponding to low (estrus) and high (proestrus) circulating estrogen. With background training in water-maze procedures, rats learned the location of an escape platform in the maze in a single session of 8 training trials. A strong spatial bias for the escape platform was also evident in a probe trial used to assess retention of learning 30 min after the training session. This entire protocol was completed in less than an hour. The performance of the estrus and proestrus rats was indistinguishable on all behavioral measures, irrespective of the stage of estrous cycle during the task. These results indicate that rapid learning and retention for spatial information over a relatively short interval may be preserved despite morphological alterations in hippocampal dendritic spine density in the normally cycling female rat. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Delayed development of place navigation compared to directional responding in young rats.

Recent work from our laboratory demonstrates that both young and adult rats show a preference for directional responding over place navigation in the Morris water task. Based on these findings, previous studies on the postnatal development of spatial learning have most likely assessed the ontogeny of directional responding instead of true place navigation. Here, we examined the development of directional responding and place navigation among young male and female rats using two variants of the Morris water task that specifically require directional and place responses. In the place variant, the hidden platform remained in the same absolute spatial location regardless of pool position. In the direction variant, the platform remained in the same direction in the room regardless of pool position. We found that ability to solve the direction task emerged around 20 to 21 days of age, whereas ability to solve the place task did not emerge until 26 to 27 days of age. These findings indicate that directional responding and place navigation exhibit different developmental trajectories and suggest that the 2 forms of navigation have different neurobiological bases. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Local inhibition of hippocampal nitric oxide synthase does not impair place learning in the Morris water escape task in rats

Recent studies have provided evidence that nitric oxide (NO) has a role in certain forms of memory formation. Spatial learning is one of the cognitive abilities that has been found to be impaired after systemic administration of an NO-synthase inhibitor. As the hippocampus has a pivotal role in spatial orientation, the present study examined the role of hippocampal NO in spatial learning and reversal learning in a Morris task in adult rats. It was found that N omega-nitro-L-arginine infusions into the dorsal hippocampus affected the manner in which the rats were searching the submerged platform during training, but did not affect the efficiency to find the spatial location of the escape platform. Hippocampal NO-synthase inhibition did not affect the learning of a new platform position in the same water tank (i.e. reversal learning). Moreover, no treatment effects were observed in the probe trials (i.e. after acquisition and after reversal learning), indicating that the rats treated with N omega-nitro-L-arginine had learned the spatial location of the platform. These findings were obtained under conditions where the NO synthesis in the dorsal hippocampus was completely inhibited. On the basis of the present data it was concluded that hippocampal NO is not critically involved in place learning in rats.     

Transient sex differences in the between-sessions but not in the within-session memory underlying an active place avoidance task in weanling rats.

Spatial abilities were tested in male and female rats by training them to avoid an area in which there was a mild footshock while the arena rotated at 1 revolution/minute. The to-be-avoided area was stable in the coordinates of the room, so extramaze landmarks had to be used for accurate navigation, as the rotation made intramaze cues and substrate-based path integration useless for the avoidance. From Postnatal Day (PD) 19, rats were trained for 22 consecutive days. When the shock area was the same across sessions male rats reached optimal performance on PDs 23–24, 10 days before female rats, but when the location of the shock changed daily there were no sex differences. The results indicate that there are separate memory components underlying spatial competence: a within-session component that develops similarly in male and female rats and a between-sessions component that lasts at least 24 hr and appears earlier in male than in female rats. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Sex differences in performance in the Morris water maze and the effects of initial nonstationary hidden platform training.

Sex differences in rats' performance on a stationary hidden-platform task (spatial task) in the Morris water maze and the effects of initial nonstationary hidden platform training (NSP training) were examined. The NSP training was designed to familiarize rats with the general requirements of the water-maze task without providing spatial information. NSP training led to faster acquisition and improved retention of the subsequent spatial task in both males and females. There was a sex difference favoring males on acquisition and retention of the spatial task only in rats that had not received previous NSP training. Moreover, there was an apparent reversed sex difference favoring females on some measures of spatial performance in NSP-trained rats. These results suggest that performance on the water-maze task, including the expression of sex differences, can be altered by previous familiarization with nonspatial aspects of the task. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

An evaluation of spatial information processing in aged rats.

The spatial learning abilities of young, middle-age, and senescent rats were investigated in 2 experiments using several versions of the Morris water maze task. In Exp I, Long-Evans hooded rats were trained to find a submerged escape platform hidden within the water maze. Aged Ss exhibited acquisition deficits compared with either young or middle-age Ss. With continued training, all age groups eventually achieved comparable asymptotic levels of performance. To identify the basis of the age-related impairments observed in Exp I, naive young and aged Ss in Exp II were initially tested for their ability to locate a cued escape platform in the water maze. The escape latencies of both young and aged Ss rapidly decreased to equivalent asymptotic levels. Following cue training, young Ss exhibit a significant spatial bias for the region of the testing apparatus where the platform was positioned during training. In contrast, aged Ss showed no spatial bias. Training was continued in Exp II using a novel submerged platform location for each S. During these place training trials, the escape latencies of senescent Ss were longer than those of young Ss. These impairments were also accompanied by a lack of spatial bias among aged Ss relative to young controls. Results indicate that age-related impairments in water maze performance reflect a specific deficit in the ability of aged rats to utilize spatial information. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Evidence for extrahippocampal involvement in place learning and hippocampal involvement in path integration

Although there is a good deal of evidence that animals require the hippocampus for learning place responses, animals with damage to the afferent and efferent fibers coursing through the fimbria-fornix have been shown to acquire a place response. This finding suggests either that the cells of the hippocampus proper (CA1-4 and dentate gyrus), via their connections to the temporal lobe, can mediate place learning or that some extrahippocampal structure is sufficient. We examined this question using rats with ibotenic acid lesions of the cells of the hippocampus. Rats were pretrained to swim to a visible platform and then given probe trials on which the visible platform was removed. Video and kinematic analyses showed that the hippocampal rats expected to find the platform at its previous location because they swam directly to that location and paused and turned at that location after the platform was removed. Additional tests confirmed that they had learned a place response. There were, however, abnormalities in their swimming patterns, and despite having acquired one place response, they did not then acquire new place responses when only the hidden platform training procedure was used. These results demonstrate that place learning can be acquired by rats in which the hippocampus proper is removed. Contrasts between conditions in which hippocampal rats acquire a place response and conditions in which they fail suggests that the hippocampus may serve as an on line system for monitoring movement and integrating movement paths.     

Cholinergic receptor blockade impairs spatial localization by use of distal cues in the rat.

Studied spatial localization in the Morris water maze. 30 male Long-Evans hooded rats were required to escape from cool water by finding a submerged, invisible platform located at a fixed place. The start point randomly varied, and there were no local cues. After training, the platform was moved. Six Ss subjected to central cholinergic receptor blockade with atropine sulfate were compared with normal Ss and with 6 Ss receiving peripheral cholinergic blockade with atropine methylnitrate. The controls were a group of blind Ss and Ss for which the platform was moved from trial to trial. Results show that controls and the atropine methylnitrate Ss used a spatial mapping strategy to locate the platform. The atropine sulfate-treated Ss adopted a search strategy like that of the blind Ss and Ss for which the platform was randomly moved. Results support the idea that central cholinergic systems are important for spatial mapping, which demands the use of distal visual cues. (33 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Mutation analysis using the restriction site mutation (RSM) assay

Although two decades of research suggests that the hippocampus plays a special role in place learning, the present paper describes a series of studies using swimming pool spatial tasks that show that hippocampal rats have considerable place learning ability, which includes the abilities of finding, remembering, and searching for places. The same studies also show that when environmental cues are uninformative, as is the case early in original learning and again in reversal learning, hippocampal rats are impaired. Since control rats quickly resolve spatial ambiguity in these situations, it is argued that they must have a system with which they can calibrate spatial cues. The discussion considers the possibility that they use dead reckoning with path integration, a spatial strategy that provides guidance based on cues generated by a point of reference and subsequent self-movement and not the cues in the environment through which they are moving. With path integration an animal can monitor its location and at the same time attach spatial meaning to cues that it encounters. An ability to recalibrate external cues may provide the tuning that allows control rats to quickly acquire place responses while hippocampal rats are constrained by the processes of associative learning.     

Cerebellar contribution to spatial event processing: Morris water maze and T-maze

Recently, a cognitive function of cerebellar networks has been challenging the traditional view of the cerebellum as a motor control centre. Among the cognitive abilities reported to be affected by cerebellar deficits is the capacity to solve a spatial problem. We investigated the influence of a cerebellar lesion on spatial abilities by behavioural analysis of rats that had undergone surgical hemicerebellectomy (HCb; HCbed rats). Experiments were performed with a Morris water maze (MWM) and a water T-maze in both cue and place versions (visible or hidden platform respectively). Results indicate a severe impairment in coping with spatial information in all phases of MWM testing as well as in the T-maze paradigm. However, if the MWM cue phase was prolonged, HCbed rats displayed some ability to learn platform position, although at a level significantly different from controls. They succeeded in finding the platform, even in a pure place paradigm, such as finding a hidden platform with the starting points sequentially changed. Retention testing was also performed, demonstrating that HCb affects acquisition but not retention of spatial information. HCbed animals exhibit such disrupted exploration behaviour that they can display only peripheral circling, and they can acquire spatial relations only when proximal cues are available. Furthermore, in all phases of testing, platform finding for HCbed animals is essentially based on place strategies. Thus, a specific pattern of spatial behaviour, markedly different from that displayed following hippocampal or cortical lesions, characterizes cerebellar lesioned rats. These results are discussed taking into account the role in procedural learning recently assigned to cerebellar networks, demonstrating that the cerebellar circuits represent the keystone of the procedural components of spatial event processing.     

Preweanling rats solve the Morris water task via directional navigation.

Adult rats show a preference for directional navigation over place navigation in the Morris water task. Here, the authors investigated whether preweanling rats with a newly developed ability to perform the water task also solve the task via directional navigation. After 24-day-old rats were trained to find a hidden platform in a fixed spatial location, a no-platform probe trial was conducted with the pool either in the same position as that used during training (no shift group) or shifted to a new position in the room (shift group). The authors found that rats in the shift group did not search for the platform at its absolute spatial location but rather navigated in the same direction that the platform was located during training and searched at the correct distance from the pool wall, resulting in a search at a location that was never trained. This pattern of results suggests that young rats learn to solve the water task by navigating in a particular direction rather than navigating to a precise place--a finding that may have implications for understanding hippocampal development. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Posttraining paradoxical sleep in rats is increased after spatial learning in the Morris water maze.

The role of posttraining paradoxical sleep (PS) in spatial or nonspatial learning in the Morris water maze was evaluated. Sprague-Dawley rats were given a 12-trial training session in either the hidden or the visible platform versions of the task. Subgroups then underwent paradoxical sleep deprivation (PSD) beginning at different times after training. Rats with PSD imposed from 14 hr after spatial training had poorer retest scores than any other group. Other rats, implanted with electrodes to permit continuous recording of sleep electroencephalography, were found to undergo a prolonged period of elevated PS after spatial training. By contrast, rats trained in the nonspatial version of the water maze task did not show retention deficits after PSD or elevated PS after training. These results support a role for PS in spatial, but not nonspatial, learning in the Morris water maze. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Influence of a beacon on spatial learning based on the shape of the test environment.

In 5 experiments rats were required to escape from a triangular shaped pool by swimming to a submerged platform. The principal group of interest in each experiment received training with a beacon attached to the platform. The purpose of the experiments was to assess if the beacon overshadowed (Experiments 1–4) or blocked (Experiment 5) learning about the position of the platform with reference to the shape of the pool. The platform was located in the center of the pool for the first 2 experiments and in a corner for the remaining experiments. Although there was an overshadowing effect in Experiment 1, the remaining experiments failed to reveal any disruptive influence of the beacon on learning based on the shape of the pool. Moreover, in Experiments 3–5 there was an indication that the beacon facilitated such learning. The results suggest that spatial learning based on the shape of a test environment may not take place in the same way as that based on more discrete landmarks. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The effect of mouthrinses containing zinc and triclosan on plaque accumulation, development of gingivitis and formation of calculus in a 28-week clinical test

The basal and depolarization-induced arginine-vasopressin (AVP) release from intact pituitaries of SHR and WKY rats was studied in vitro in a perfusion chamber. Differences associated to strain, sex and two age periods (pre-adult: 25-30 days of age; adult: 60-70 days of age) were assessed. The results show an enhanced AVP release in the adult male as well as female SHR compared to the WKY rat. The stimulated AVP release was also significantly higher in the preadult male SHR and indicated in preadult females SHR. No differences associated to strain in basal AVP release were detected at the age interval 25-30 days. The response to muscimol was increased in preadult female and male SHR rats compared to the WKY animals. It is concluded that the augmented depolarization-induced AVP release and sensitivity to muscimol in the SHR is not related to sex, and no apparent change in this pattern was associated to the transition between the juvenile and adult condition.     

The effects of combined lesions of the subicular complex and the entorhinal cortex on two forms of spatial navigation in the water maze.

The role of the subicular complex and entorhinal cortex (SUB–EC) in spatial learning was examined in 2 water maze experiments. In Experiment 1, rats had to locate a hidden platform that was always a fixed distance and direction from an intramaze landmark. Each day, the landmark and platform were moved to a new location. Both control and SUB–EC-lesioned rats learned to locate the platform equally readily during training. However, the control group was impaired in locating the platform when the visual extramaze cues were concealed, whereas the lesioned group was unaffected by this manipulation. In Experiment 2, the lesioned rats were impaired in finding a hidden platform that was in a fixed place in the water maze and showed no evidence of having learned its location in a probe test. These results suggest that damage to the SUB–EC impairs the integration of geometric information but spares a more general navigational-directional strategy. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Vernier and grating acuity in adult hooded rats: The influence of sex.

Although morphological sex differences are pervasive in the primary visual cortex of hooded rats, it is not known whether sex differences occur in vision in these rats. In this study, grating acuity was measured in a forced-choice Y maze and a jumping stand in adult hooded rats, and vernier acuity thresholds were established in the jumping stand. With a criterion of 34 correct/50 trials, the number of correct choices for both sexes was high (1.0–1.6 cycles per degree [c/deg]) for spatial gratings. Female rats made more correct identifications of the coarse gratings (0.125 and 0.25 c/deg) than male rats, but no sex differences were found for higher spatial frequencies. In contrast, male rats were better at detecting smaller vernier offsets in both the individual criterion and group averages than female rats, and all of the rats detected vernier misalignments at 34.1 min (equivalent to 1.75 c/deg), which is above their grating acuity. Vernier acuity may mirror some sex differences in visual cortex anatomy. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Treatment of unresectable hepatocellular carcinoma with lipiodol chemoembolization: a multicenter randomized trial. Groupe CHC

We investigated the effect of successive administrations of SA4503 (1-(3,4-dimethoxyphenethyl)-4-(3-phenylpropyl)piperazine dihydrochloride), a novel cognitive enhancer with high affinity and selectivity for the sigma1 receptor subtype, on the cortical cholinergic dysfunction-induced impairment of the spatial learning performance in the Morris water maze (MWM) task in rats. The impairment of the spatial learning performance was produced by the ibotenic acid-induced lesion of the basal forebrain (BF) area in rats. Escape latencies to find the platform during the training trials of the MWM task were significantly prolonged in the BF-lesioned rats compared with the sham-operated rats. Daily treatment with SA4503 (0.1-0.5 mg/kg, P.O./day) for 13 days ameliorated this learning deficit. In the probe trial, BF-lesioned rats reduced the number of times each rat crossed the former platform location during the training trials (goal area) in comparison with sham-operated rats. Successive administrations of SA4503 (0.25 mg/kg, P.O./day) also significantly increased the BF lesion-induced reduction of the number of times each rat crossed the goal area. These results suggest that the successive administrations of SA4503 attenuate the impairment of the spatial learning performance in rats with cortical cholinergic dysfunction, and that SA4503 is useful as a therapeutic drug for Alzheimer's disease.     

Lack of task specificity and absence of posttraining effects of atropine on learning.

Three experiments, with 91 male Lister rats, examined the effect of the cholinergic antagonist atropine on the acquisition of learning tasks known to be sensitive or insensitive to impairment by hippocampal lesions, on the retention of performance acquired in the absence of the drug, and on memory consolidation immediately after daily training trials. In Exp I, intraperitoneal atropine sulfate (10 or 50 mg/kg) injected 30 min prior to training severely impaired learning of both spatial and nonspatial discrimination tasks when compared with saline or atropine methylnitrate (50 mg/kg). In Exp II, atropine sulfate (50 mg/kg) also impaired spatial discrimination accuracy in Ss previously trained to asymptote under drug-free conditions. These deficits were not due to either peripheral drug effects of gross sensorimotor impairments. In Exp III, daily posttraining injections of atropine sulfate (50 mg/kg) failed to influence either learning or subsequent retention of place navigation in Ss trained to find a single hidden escape platform. The data confirm that profound learning deficits occur when training is conducted under atropine but offer no support to the hypotheses that cholinergic neurons play an important role in memory consolidation or other posttraining processes. Results demonstrate dissimilarities between the behavioral impairments induced by cholinergic blockade and hippocampal lesions under appropriate test regimes. (50 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Absence of snapshot memory of the target view interferes with place navigation learning by rats in the water maze.

Contribution of visual and nonvisual mechanisms to spatial behavior of rats in the Morris water maze was studied with a computerized infrared tracking system, which switched off the room lights when the S entered the inner circular area of the pool with an escape platform. 10 naive male rats trained under light–dark (LD) conditions found the escape platform more slowly than 10 male rats trained in permanent light (LT). After group members were swapped, the LT-pretrained rats found under LD conditions the same target faster and eventually approached latencies attained during LT navigation. Performance of LD-trained rats deteriorated in permanent darkness (PD) but improved with continued PD training. Thus LD navigation improves gradually by procedural learning (extrapolation of the start-target azimuth into the zero-visibility zone) but remains impaired by lack of immediate visual feedback rather than by absence of the snapshot memory of the target view. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Visits to starts, routes, and places by rats (Rattus norvegicus) in swimming pool navigation tasks.

In 2 studies, 40 young adult female Sprague-Dawley rats were trained to escape to visible or to hidden platforms in a swimming pool and then given probe trials, which required that they searched for a platform that had been removed or repositioned. Results indicate that to solve the tasks, Ss simultaneously used a number of behavioral strategies including position responses, cue responses, and place responses. On the probe trials, they not only displayed behaviors that were reinforced during training but also displayed novel behaviors. Ss trained on the place task (hidden platform) made more swims across the platform's previous location, whereas Ss trained on the cue task (visible platform) made more returns to previously used start points. Increases in the number of start points produced more returns to start points, whereas increases in the number of platform locations produced more searches for platforms. It is concluded that rats make coextensive use of all relevant strategies to solving spatial navigation tasks and that their search patterns on probe trials reflect both previously reinforced behaviors and novel unconditioned search behaviors. (34 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)