Preserved learning about allocentric cues but impaired flexible memory expression in rats with hippocampal lesions

Several studies have shown that slight modifications in the standard reference spatial memory procedure normally used for allocentric learning in the Morris water maze and the radial maze, can overcome the classic deficit in allocentric navigation typically observed in rats with hippocampal damage. In these special paradigms, however, there is only intramaze manipulation of a salient stimulus. The present study was designed to investigate whether extramaze manipulations produce a similar outcome. With this aim a four-arm plus-shaped maze and a reference spatial memory paradigm were used, in which the goal arm was marked in two ways: by a prominent extramaze cue (intermittent light), which maintained a constant relation with the goal, and by the extramaze constellation of stimuli around the maze. Experiment 1 showed that, unlike the standard version of the task, using this special training procedure hippocampally-damaged rats could learn a place response as quickly as control animals; importantly, one day after reaching criterion, lesioned and control subjects performed the task perfectly during a transfer test in which the salient extramaze stimulus used during the acquisition was removed. However, although acquisition deficit was overcomed in these lesioned animals, a profound deficit in retention was detected 15 days later. Experiment 2 suggests that although under our special paradigm hippocampal rats can learn a place response, spatial memory only can be expressed when the requisites of behavioral flexibility are minimal. These findings suggest that, under certain circumstances, extrahippocampal structures are sufficient for building a coherent allocentric representation of space; however, flexible memory expression is dependent, fundamentally, on hippocampal functioning.     

Place and response learning of rats in a Morris water maze: differential effects of fimbria fornix and medial prefrontal cortex lesions

The question examined in this study is concerned with a possible functional dissociation between the hippocampal formation and the prefrontal cortex in spatial navigation. Wistar rats with hippocampal damage (inflicted by a bilateral lesion of the fimbria fornix), rats with damage to the medial prefrontal cortex, and control-operated rats were examined for their performance in either one of two different spatial tasks in a Morris water maze, a place learning task (requiring a locale system), or a response learning task (requiring a taxon system). Performance of the classical place learning (allocentric) task was found to be impaired in rats with lesions of the fimbria fornix, but not in rats with damage of the medial prefrontal cortex, while the opposite effect was found in the response learning (egocentric) task. These findings are indicative of a double functional dissociation of these two brain regions with respect to the two different forms of spatial navigation. When the place learning task was modified by relocating the platform, the impairment in animals with fimbria fornix lesions was even more pronounced than before, while the performance of animals with medial prefrontal cortex lesions was similar to that of their controls. When the task was again modified by changing the hidden platform for a clearly visible one (visual cue task), the animals with fimbria fornix lesions had, at least initially, shorter latencies than their controls. By contrast, in the animals with medial prefrontal cortex damage this change led to a slight increase in escape latency.     

Dissociation of Hippocampal and Striatal Contributions to Spatial Navigation in the Water Maze

Two experiments were conducted to compare the effects of fornix/fimbria and caudate-putamen lesions in Long–Evans hooded rats (Rattus norvegicus) trained on two water maze tasks that differed in the type of spatial localization required for optimum solution. In Experiment 1, the lesioned rats and surgical controls were trained on the standard place task in the water maze (Morris, 1981) and given two postacquisition tests (a platform removal probe and platform relocation test). In Experiment 2, rats with similar lesions and control rats were trained on a modified cue navigation task. Fornix/fimbria lesions impaired a late stage of place task acquisition but did not impair acquisition of the cue task. Caudate-putamen lesions resulted in a severe place acquisition impairment and a transient cue acquisition impairment, both of which were characterized by an initial tendency to swim near the wall of the pool. Post-hoc analyses of the direction and angles of departure from the start points suggested that rats with fornix/fimbria lesions used non-allocentric spatial strategies to solve the place task. These rats also demonstrated a significantly weakened spatial bias for the former training quadrant on the platform removal probe and reduced flexibility in navigating to a novel platform location on the platform relocation test. In contrast, rats with caudate-putamen lesions showed a significant spatial bias for the former training quadrant but failed to cross the exact location within the quadrant where the platform was formerly positioned. The results suggest that the hippocampus mediates the allocentric spatial component of the water maze place task while the dorsomedial striatum may play an important role in the acquisition of the procedural aspects of both place and cue versions of the task.     

Cue effects on memory for location when navigating spatial displays

Participants maneuvered a rat image through a circular region on the computer screen to find a hidden target platform, blending aspects of two well-known spatial tasks. Like the Morris water maze task, participants first experienced a series of learning trials before having to navigate to the hidden target platform from different locations and orientations. Like the dot-location task, they determined the location of a position within a two-dimensional circular region. This procedure provided a way to examine how the number of surrounding cues (1, 2, or 3) affects the memory for spatial location in navigation. Memory performance was better when there were more cues and when targets were close to cues, consistent with the idea that cues bolster fine-grain memory, especially in proximal regions. Early and late measures of bias in memory reflected biases in a direction toward the nearest cue, implicating a cue-based category structure of the navigational space. Collectively, results suggest cue-based spatial memory representations that have been inferred from the dot-location task generalize to a navigation task within a simple, computer-based environment, as demonstrated by the good fits of the spatial model developed for the dot-location task ( Fitting, Wedell, & Allen, 2005, 2007 ).     

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.     

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.     

Proximal versus distal cue utilization in spatial navigation: the role of visual acuity?

Proximal versus distal cue use in the Morris water maze is a widely accepted strategy for the dissociation of various problems affecting spatial navigation in rats such as aging, head trauma, lesions, and pharmacological or hormonal agents. Of the limited number of ontogenetic rat studies conducted, the majority have approached the problem of preweanling spatial navigation through a similar proximal-distal dissociation. An implicit assumption among all of these studies has been that the animal's visual system is sufficient to permit robust spatial navigation. We challenged this assumption and have addressed the role of visual acuity in spatial navigation in the preweanling Fischer 344-N rat by training animals to locate a visible (proximal) or hidden (distal) platform using double or null extramaze cues within the testing environment. All pups demonstrated improved performance across training, but animals presented with a visible platform, regardless of extramaze cues, simultaneously reached asymptotic performance levels; animals presented with a hidden platform, dependent upon location of extramaze cues, differentially reached asymptotic performance levels. Probe trial performance, defined by quadrant time and platform crossings, revealed that distal-double-cue pups demonstrated spatial navigational ability superior to that of the remaining groups. These results suggest that a pup's ability to spatially navigate a hidden platform is dependent on not only its response repertoire and task parameters, but also its visual acuity, as determined by the extramaze cue location within the testing environment. The standard hidden versus visible platform dissociation may not be a satisfactory strategy for the control of potential sensory deficits.     

Constructing representations of spatial location from briefly presented displays

Spatial memory and reasoning rely heavily on allocentric (often map-like) representations of spatial knowledge. While research has documented many ways in which spatial information can be represented in allocentric form, less is known about how such representations are constructed. For example: Are the very early, pre-attentive parts of the process hard-wired, or can they be altered by experience? We addressed this issue by presenting sub-saccadic (53 ms) masked stimuli consisting of a target among one to three reference features. We then shifted the location of the feature array, and asked participants to identify the target’s new relative location. Experience altered feature processing even when the display duration was too short to allow attention re-allocation. The results demonstrate the importance of early perceptual processes in the creation of representations of spatial location, and the malleability of those processes based on experience and expectations.     

Evidence of separable spatial representations in a virtual navigation task

Three experiments investigated spatial orientation in a virtual navigation task. Subjects had to adjust a homing vector indicating their end position relative to the origin of the path. It was demonstrated that sparse visual flow was sufficient for accurate path integration. Moreover, subjects were found to prefer a distinct egocentric or allocentric reference frame to solve the task. "Turners" reacted as if they had taken on the new orientation during turns of the path by mentally rotating their sagittal axis (egocentric frame). "Nonturners," by contrast, tracked the new orientation without adopting it (allocentric frame). When instructed to use their nonpreferred reference frame, both groups displayed no decline in response accuracy relative to their preferred frame; even when presented with reaction formats based on either ego or allocentric coordinates, with format unpredictable on a trial, both groups responded highly accurately. These findings support the assumption of coexisting spatial representations during navigation.     

Remembering the past and imagining the future: a neural model of spatial memory and imagery

The authors model the neural mechanisms underlying spatial cognition, integrating neuronal systems and behavioral data, and address the relationships between long-term memory, short-term memory, and imagery, and between egocentric and allocentric and visual and ideothetic representations. Long-term spatial memory is modeled as attractor dynamics within medial-temporal allocentric representations, and short-term memory is modeled as egocentric parietal representations driven by perception, retrieval, and imagery and modulated by directed attention. Both encoding and retrieval/imagery require translation between egocentric and allocentric representations, which are mediated by posterior parietal and retrosplenial areas and the use of head direction representations in Papez's circuit. Thus, the hippocampus effectively indexes information by real or imagined location, whereas Papez's circuit translates to imagery or from perception according to the direction of view. Modulation of this translation by motor efference allows spatial updating of representations, whereas prefrontal simulated motor efference allows mental exploration. The alternating temporal-parietal flows of information are organized by the theta rhythm. Simulations demonstrate the retrieval and updating of familiar spatial scenes, hemispatial neglect in memory, and the effects on hippocampal place cell firing of lesioned head direction representations and of conflicting visual and ideothetic inputs.     

Place navigation in mammals: a configuration-based model

Recent water maze experiments suggest that rats performing place navigation primarily use the geometric information provided by a set of landmarks, and neglect the featural information provided by the identities of the landmarks. Here, I develop a model that explains how an animal may perform place navigation by relying only on geometric information. The core of the model is the representation of places as panoramas defined by circular bar-codes embodying the relative bearings and apparent sizes of the landmarks, irrespective of their identities. There are two stages in the model. During the first stage, the animal freely explores its environment in order to acquire spatial information at the local level. During the second stage, the animal uses the information previously memorized to perform place navigation towards the goal it intends to reach. The possible role of two brain areas in place navigation is discussed within this framework. Beyond their primary role in landmark-based representations of places, hippocampal place cells may be involved in computing the current distances to the landmarks. Beyond their primary role in landmark-based representations of headings, post-subicular head-direction cells may be involved in computing the “compass bearings” of the landmarks. Received: 17 January 1998 / Accepted after revision: 19 April 1998     

Caudate nucleus and memory for egocentric localization

A large body of evidence suggests that the caudate nucleus (CN) plays a critical role in the processing of spatial localization information. Furthermore, evidence has begun to accumulate that the CN is involved in the processing of a very specific class of spatial cues, namely, egocentric cues (localization with reference to the organism). This is in contrast to allocentric localization, where an organism localizes on the basis of cues external to the organism. One would then predict that lesions to the CN should disrupt performance on any tasks that depend chiefly on egocentric spatial cues, while leaving performance on allocentric tasks intact. To test this prediction, two groups of rats were trained on two different egocentric memory tasks and two different allocentric memory tasks. Specifically, one group of rats was trained on an adjacent-arm (egocentric) and an 8-arm radial maze task (allocentric). A second group of rats was trained on a right-left discrimination (egocentric) and a place-learning task (allocentric). After training, both groups received bilateral lesions of the CN. Results showed that CN-lesioned animals were profoundly impaired on retention of the egocentric tasks. In sharp contrast to this, the same animals were not or were only transiently impaired or transiently affected on allocentric tasks. Sham-operated controls were either unimpaired or transiently affected on all tasks. These findings further support the idea that the CN plays a critical modulatory role in the processing of egocentric spatial and not allocentric spatial cues.     

Learning associated increase in heat shock cognate 70 mRNA and protein expression

The Morris water maze is a task widely used to investigate cellular and molecular changes associated with spatial learning and memory. This task has both spatial and aversive (swimming related stress) components. It is possible that stress may influence cellular modifications observed after learning the Morris water maze spatial task. Heat shock proteins, also known as stress proteins, are up-regulated in response to thermal stress, trauma, or environmental insults. In the rat hippocampus, psychophysiological stress increases the levels of heat shock protein 70 (HSC70). In this study, we investigated whether the expression of the hsc70 gene is modulated in the hippocampus during learning of the Morris water maze task. Five groups of rats were trained in the Morris water maze task for varying amounts of time (either 1, 2, 3, 4, or 5 days). Training consisted of 10 trials/day in which the animals were given 60s to find a submerged platform. Rats were sacrificed 24h after their last training trial. Results showed a significant increase in hsc70 mRNA and protein levels in the hippocampal formation after two and three days of training, respectively. The increase in mRNA and protein was associated with learning but not stress because the increase was not observed in the yoked control animals. These findings suggest that cellular and molecular changes can occur independent of stress. Moreover, the results are the first to implicate hsc70 expression in spatial learning.     

Asymmetric learning transfer between imagined viewer- and object-rotations: Evidence of a hierarchical organization of spatial reference frames

Neural resources subserving spatial processing in either egocentric or allocentric reference frames are, at least partly, dissociated. However, it is unclear whether these two types of representations are independent or whether they interact. We investigated this question using a learning transfer paradigm. The experiment and material were designed so that they could be used in a clinical setting. Here, we tested healthy subjects in an imagined viewer-rotation task and an imagined object-rotation task. The order of the tasks was counterbalanced across subjects. The results showed that subjects who did the viewer-rotation task first had fewer errors and shorter latencies of response in the object-rotation task, whereas subjects who did the object-rotation task first had little if any advantage in the viewer-rotation task. In other words, the results revealed an asymmetric learning transfer between tasks, which suggests that spatial representations are hierarchically organized. Specifically, the results indicate that the viewer-rotation task engaged allocentric representations and egocentric representations, whereas the object-rotation task engaged only egocentric representations.     

Asymmetric learning transfer between imagined viewer- and object-rotations: Evidence of a hierarchical organization of spatial reference frames

Neural resources subserving spatial processing in either egocentric or allocentric reference frames are, at least partly, dissociated. However, it is unclear whether these two types of representations are independent or whether they interact. We investigated this question using a learning transfer paradigm. The experiment and material were designed so that they could be used in a clinical setting. Here, we tested healthy subjects in an imagined viewer-rotation task and an imagined object-rotation task. The order of the tasks was counterbalanced across subjects. The results showed that subjects who did the viewer-rotation task first had fewer errors and shorter latencies of response in the object-rotation task, whereas subjects who did the object-rotation task first had little if any advantage in the viewer-rotation task. In other words, the results revealed an asymmetric learning transfer between tasks, which suggests that spatial representations are hierarchically organized. Specifically, the results indicate that the viewer-rotation task engaged allocentric representations and egocentric representations, whereas the object-rotation task engaged only egocentric representations.     

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.     

Sex differences in dogs’ social learning of spatial information

We used a modified version of the Do as I Do paradigm to investigate dogs’ preference and flexibility in the acquisition of different types of spatial information in social learning situations. When required to match the location of the demonstration, dogs (N = 16) preferentially relied on allocentric information, i.e., the relationship between the location of the demonstration and the various objects surrounding it. However, when allocentric cues were inadequate to solve the task, dogs learned to rely on egocentric information, i.e., the direction—left/right—taken by the human demonstrator. The ease of resorting to the non-preferred egocentric strategy was sex-dependent with males acquiring the egocentric strategy in fewer trials than females. This study shows that dogs rely preferentially on allocentric cues when recalling socially acquired spatial information. However, they are impressively flexible in switching to egocentric strategies according to the task requirements. Whether preference for the allocentric strategy in processing spatial information is embedded in the nature of social learning or restricted to our paradigm is an open question. This study also supports the idea that sex differences in cognitive domains are widespread among mammals and calls for further investigations aimed at shedding light on the evolution, function and mechanisms of such differences.     

Evidence for the substantia nigra pars compacta as an essential component of a memory system independent of the hippocampal memory system

The aim of the present study was to test if the nigrostriatal pathway is an essential component for a water maze cued task learning and if it works independently of the hippocampal memory system. This hypothesis was tested using an animal model of Parkinson's disease in which male Wistar rats were lesioned in the substantia nigra pars compacta (SNc) by the intranigral infusion of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), thus causing a partial depletion of striatal dopamine. SNc-lesioned and sham-operated animals were implanted bilaterally with guide cannulae above the dorsal hippocampus in order to be tested after the administration of 0.4 microl 2% lidocaine or saline into this structure. The animals were tested in a spatial or in a cued version of the water maze, memory tasks previously reported to model hippocampal-dependent spatial/relational and striatal-dependent S-R learning, respectively. Hippocampal inactivation, but not SNc lesion, impaired learning and memory in the spatial version of the water maze. An opposite situation was observed with the cued version. No significant interaction was observed between the SNc lesion and hippocampal inactivation conditions affecting scores in the spatial or in the cued version of the water maze. These results suggest that the nigrostriatal pathway is an essential part of the memory system that processes S-R learning and that it works independently of the hippocampal memory system that processes spatial/relational memories.     

Individual differences in anxiety trait are related to spatial learning abilities and hippocampal expression of mineralocorticoid receptors

Although high levels of anxiety might be expected to negatively influence learning and memory, it remains to be shown whether individual differences in anxiety may influence spatial learning and memory in outbred rat populations. We have studied this possibility in male Wistar rats whose levels of anxiety were first characterized as either high (HA) or low (LA) according to their behavior in the elevated plus maze or in the open field test. Subsequently, their performance in the Morris water maze was studied, a task dependent on hippocampal activity. Interestingly, LA rats showed a faster acquisition and better memory in the water maze when compared to HA rats. Indeed, this difference in performance could mainly be attributed to the increase in thigmotactic behavior (swimming in circles close to the maze walls) displayed by HA rats during spatial navigation. Glucocorticoids are known to affect the state of anxiety and the hippocampus is the main target of glucocorticoids in the brain. Hence, we investigated whether the hippocampal expression of the two classical corticosteroid receptors, mineralocorticoid (MR) and glucocorticoid (GR) differed in the two groups of rats. We found that LA rats displayed higher hippocampal expression of MR but not GR than HA rats. Indeed, the expression levels for these receptors were positively correlated with the amount of time spent by the animals in the open arms of the elevated plus maze. Moreover, we present evidence that the levels of anxiety quantified in the first stages of our study constitute a trait rather than a state. Taken together, this study has generated evidence of a close interaction between the anxiety trait, hippocampal MR expression and the learning abilities of individuals in stressful spatial orientation tasks.