Water maze swim path analysis based on tracking coordinates

In the Morris water maze, a task widely used to study spatial learning and memory in laboratory rodents, several parameters are employed to estimate cognitive abilities of animals by analyzing their swim path characteristics. An isolated view based on any one of these parameters is not always satisfactory, so multivariate procedures (factor analyses) are used to weight the parameters in context with the others. This method sheds light on some subtle differences in experimental animals’ spatial memories or strategies. However, this approach has some subjective problems, because the definition of the parameters depends on the experimenter’s opinion of appropriate measures; therefore, we suggest a bottom-up rather than a top-down analysis of swim paths by means of spatial coordinates. In the present study, swim paths were normalized to 100-element vectors and then subjected to a principal components analysis. Swim paths could be sufficiently described in terms of only three components, each of which accounted for specific characteristics of the trajectories. We found significant differences in swim path patterns between test groups of rats that could not be discriminated via standard water maze parameters. Thus, the components can be related to different aspects of spatial cognition not detectable by commonly used parameters.     

Reinforcement as a mediator of the perception of humans by horses (Equus caballus)

A central question in the interspecific human/animal relationship is how domestic animals perceive humans as a significant element of their environment. In this study, we tested the hypothesis that the use of positive or negative reinforcement in horse training may have consequences on the animals’ perception of humans, as a positive, negative or neutral element. Two groups of ponies were trained to walk backwards in response to a vocal order using either positive or negative reinforcement. Heart rate monitors and behavioural observations were used to assess the animals’ perception of humans on the short (just after training) and long (5 months later) terms. The results showed that the type of reinforcement had a major effect on the subsequent animals’ perception of familiar and unfamiliar humans. Negative reinforcement was rapidly associated with an increased emotional state, as revealed by heart rate measurements and behavioural observations (head movements and ears laid back position). Its use led the ponies to seek less contact with humans. On the contrary, ponies trained with positive reinforcement showed an increased interest in humans and sought contact after training. This is especially remarkable as it was reached in a maximum of 5 sessions of 1 to 3 min (i.e. 5 to 15 min) and had lasting effects (visible after 5 months). Even learning was positively influenced by positive reinforcement. Overall, horses seem capable of associating humans to particular experiences and display extended long-term memory abilities.     

Use of human-given cues by domestic dogs (Canis familiaris) and horses (Equus caballus)

Sixteen domestic dogs (Canis familiaris) and four horses (Equus caballus) were tested for their ability to use human-given manual and facial cues in an object-choice task. Two of the four horses used touch as a cue and one horse successfully used pointing. The performance of the dogs was considerably better, with 12 subjects able to use pointing as a cue, 4 able to use head orientation and 2 able to use eye gaze alone. Group analysis showed that the dogs performed significantly better in all experimental conditions than during control trials. Dogs were able to use pointing cues even when the cuer’s body was closer to the incorrect object. Working gundogs with specialised training used pointing more successfully than pet dogs and gundog breeds performed better than non-gundog breeds. The results of this experiment suggest that animals’ use of human given communicative signals depends on cognitive ability, the evolutionary consequences of domestication and enculturation by humans within the individual’s lifetime. Received: 15 July 1999 / Accepted after revision: 10 January 2000     

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.     

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.     

Posttraining androgens' enhancement of cognitive performance is temporally distinct from androgens' increases in affective behavior

Steroid hormone-induced variations in spatial learning and memory tasks have been reported. In this study, androgens’ effects in various cognitive and affective tasks were investigated in order to determine whether any observed differences in cognitive performance could be due to affective changes produced by the hormones. Ovariectomized rats (N = 72) received 0.0, 3.0, or 7.5 mg/kg subcutaneously, of testosterone (T), dihydrotestosterone (DHT), or 5α-androstane-3α, 17β-diol (3a-Diol) suspended in 10% ethanol/sesame oil v/v. For the cognitive tasks (Y maze, inhibitory avoidance, and object recognition), subjects were injected after training trials. For the affective tasks (open field, elevated plus maze, and tailflick), subjects were injected 1 or 24 h before testing. Posttraining injections that produced physiological concentrations of androgens - T, DHT, and 3α-Diol - 1 h later increased the percentage of correct choices in the Y maze, the latencies to cross to the shock-associated side of the inhibitory avoidance chamber, and percentage of time exploring novel objects 24 h later, when androgen levels were no longer increased. Administration of T, DHT, and 3α-Diol also increased the number of entries into the center squares of a brightly lit open field, open-arm time in the elevated plus maze, and tailflick latencies 1 but not 24 h following administration. These findings suggest that these androgens, when administered following training, can enhance cognitive performance in the tasks investigated 24 h later when androgen levels nadir, but overt changes in the affective behaviors examined occurred at the time of physiological concentrations 1 h but not 24 h following androgen administration. These findings suggest posttraining androgens can enhance consolidation and cognitive performance, independent of their anxiolytic actions.     

Aspects of spatial cognition in capuchins (Cebus apella): frames of reference and scale of space

Frames of reference (i.e. sets of loci defining spatial locations) determine animals’ performances in object search tasks. Reference frames are used at different scales. Although much behavioural research has been conducted on search strategies in many animal species, relatively little has been done on nonhuman primates. The two experiments reported here focused on the relative strength and the level of functioning of different reference frames at the small-scale level in four capuchins (Cebus apella). Two identical boxes and a landmark were placed on a round platform that could be rotated. A reward was hidden in subject’s view under one box, and then a sash-screen was lowered to hide the rotation of the platform; the sash-screen was then lifted and the subject allowed to search for the reward. In experiment 1 the rewarded box was always the closer to the landmark, in experiment 2 it could be either the box closer to or the box farther from the landmark. Capuchins were successful after invisible rotations in experiment 1, but they failed after invisible rotations in experiment 2. Two possible explanations are proposed: (1) capuchins relied heavily on the left-right body-axis as a frame, and they could only substitute it with a simple association between the rewarded position and the landmark; or (2) capuchins failed because they chose external cues in the room, therefore on a inappropriate scale. The latter explanation allows two further inferences: (a) the capuchins’ choice was indirectly related to their body-axes; and (b) the capuchins revealed a cognitive asymmetry between small-scale and large-scale spaces, thus differing from humans. Received: 10 October 1999 / Accepted after revision: 4 May 2000     

Reliability, Distribution, and Validity of Age-Related Cognitive Deficits in the Morris Water Maze

In the present study, F-344 rats throughout 1.5 to 26 months of age were tested in the reference memory version, a moving-platform repeated acquisition version, and in a cued platform version of the Morris water maze. The results suggest that: (1) performance in the water maze declines continuously, beginning at the earliest age, and very closely fits a linear function; (2) there are robust, reliable differences between individuals in terms of their performance in the Morris water maze, but chronological age accounts for only a fraction of the variance between individuals; (3) there is no evidence of a bimodal distribution among aged rats—there is no distinct subgroup of individuals that performs so poorly that they are qualitatively different from the majority of the population, and distinctions between “impaired” and “unimpaired” subjects must be based on arbitrary criteria that may not be consistent from one study to the next; (4) age-related deficits in the Morris water maze may not be restricted to learning and memory, but may also include deficits in attention, the ability to process spatial information, and/or the ability to develop efficient spatial search strategies; and (5) swim distance is the most appropriate measure of cognitive function in the Morris water maze, but the relationship between this measure and other measures of noncognitive function make it clear that swim distance may not be a pure measure of cognitive function. Although the Morris water maze remains a valuable preclinical test with better validity and specificity than many other behavioral tests, measures of performance in the Morris water maze should not be considered synonymous with cognitive function.     

Animal Disenhancement for Animal Welfare: The Apparent Philosophical Conundrums and the Real Exploitation of Animals. A Response to Thompson and Palmer

In his paper “The Opposite of Human Enhancement: Nanotechnology and the Blind Chicken problem” (Nanoethics 2: 305-36, 2008) Thompson argued that technological attempts to reduce or eliminate selected non-human animals’ capabilities (animal disenhancements) in order to solve or mitigate animal welfare problems in animals’ use pose a philosophical conundrum, because there is a contradiction between rational arguments in favor of these technological interventions and intuitions against them. In her response “Animal Disenhancement and the Non-Identity Problem: A Response to Thompson” (Nanoethics 5:43–48, 2011), Palmer maintained that the philosophical conundrum is even deeper if we introduce the non-identity problem into the discussion. In my brief response, I claim that in order to avoid the pitfalls of speculative ethics, empirical facts related to the technologies involved as well as costs for the non-human animals have to be taken into account. Depending on which changes we are referring to, ethical problems can be seen very differently. Widening the consideration to the socio-economic context in which non-human animals are currently used by humans, I challenge the idea of genuine philosophical conundrums from an antispeciesist and abolitionist perspective. Only in a context of exploitation, in which non-human animals are deprived of basic rights and their existence is totally dependent on human exploitation, the contradictions between improvement of welfare and disenhancement of capabilities make sense.     

Effects of Unilateral Entorhinal Cortex Lesion on Retention of Water Maze Performance

In a previous study, adult male Sprague-Dawley rats with unilateral, electrolytic entorhinal cortex lesions showed significant deficits in acquisition of a water maze task that measured working memory. The 10 days of testing used two trials per day with an intertrial interval of 1 h, and the rats with entorhinal damage were impaired in total distance to the platform in both trials. In the present retention study, rats who learned the same task prior to injury and were then retested for 5 days after lesion showed only a first day deficit in total distance to platform in the second trial. Analysis of swim patterns indicated that rats with unilateral entorhinal lesions used an altered strategy in retention testing to find the platform in the second trial of each day and incorporated the use of headings appropriate for Trial 1 only. This altered or compensatory strategy was not the optimum choice for problem solution. Although the rats then were able to switch headings and find the platform without significant impairment in total distance to platform on days 2–5 of testing, the use of an initial incorrect strategy indicated subtle residual deficits in cue integration and use of working memory.     

Realization,explanation and the mind-body relation

The Morris water maze has been put forward in the philosophy of neuroscience as an example of an experimental arrangement that may be used to delineate the cognitive faculty of spatial memory (e.g., Craver and Darden, Theory and method in the neurosciences, University of Pittsburgh Press, Pittsburgh, 2001; Craver, Explaining the brain: Mechanisms and the mosaic unity of neuroscience, Oxford University Press, Oxford, 2007). However, in the experimental and review literature on the water maze throughout the history of its use, we encounter numerous responses to the question of “what” phenomenon it circumscribes ranging from cognitive functions (e.g., “spatial learning”, “spatial navigation”), to representational changes (e.g., “cognitive map formation”) to terms that appear to refer exclusively to observable changes in behavior (e.g., “water maze performance”). To date philosophical analyses of the water maze have not been directed at sorting out what phenomenon the device delineates nor the sources of the different answers to the question of what. I undertake both of these tasks in this paper. I begin with an analysis of Morris’s first published research study using the water maze and demonstrate that he emerged from it with an experimental learning paradigm that at best circumscribed a discrete set of observable changes in behavior. However, it delineated neither a discrete set of representational changes nor a discrete cognitive function. I cite this in combination with a reductionist-oriented research agenda in cellular and molecular neurobiology dating back to the 1980s as two sources of the lack of consistency across the history of the experimental and review literature as to what is under study in the water maze.     

Artifice and virtue in the<Emphasis Type="Italic">Xunzi</Emphasis>

Xunzi was chronologically the third of the three great Confucian thinkers of China’s classical period, after Confucius and Mencius. Having produced the most comprehensive philosophical system of that period, he occupies a place in the development of Chinese philosophy comparable to that of Aristotle in the Western philosophical tradition. This essay reveals how Xunzi’s understanding of virtue and moral development dovetailed with his positions on ritual propriety, the attunement of names, the relation betweenli (patterns) andlei (categories), and his view ofdao (the way) in general. I have argued for a “constructivist” understanding of each of these aspects of Xunzi’s philosophy in some detail elsewhere (see Hagen 2000, 2001, 2002, 2003), and so here I will just briefly review a few key points before addressing their relation to moral development.     

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.     

A Necessity for MAP Kinase Activation in Mammalian Spatial Learning

Although the biochemical mechanisms underlying learning and memory have not yet been fully elucidated, mounting evidence suggests that activation of protein kinases and phosphorylation of their downstream effectors plays a major role. Recent findings in our laboratory have shown a requirement for the mitogen-activated protein kinase (MAPK) cascade in hippocampal synaptic plasticity. Therefore, we used an inhibitor of MAPK activation, SL327, to test the role of the MAPK cascade in hippocampus-dependent learning in mice. SL327, which crosses the blood-brain barrier, was administered intraperitoneally at several concentrations to animals prior to cue and contextual fear conditioning. Administration of SL327 completely blocked contextual fear conditioning and significantly attenuated cue learning when measured 24 hr after training. To determine whether MAPK activation is required for spatial learning, we administered SL327 to mice prior to training in the Morris water maze. Animals treated with SL327 exhibited significant attenuation of water maze learning; they took significantly longer to find a hidden platform compared with vehicle-treated controls and also failed to use a selective search strategy during subsequent probe trials in which the platform was removed. These impairments cannot be attributed to nonspecific effects of the drug during the training phase; no deficit was seen in the visible platform task, and injection of SL327 following training produced no effect on the performance of these mice in the hidden platform task. These findings indicate that the MAPK cascade is required for spatial and contextual learning in mice.     

Age-Related Changes in Plasma Catecholamine Responses to Acute Swim Stress

Young adult (3 months) and aged (22 months) Fischer 344 male rats were prepared with chronic tail artery catheters. Three days after surgery, rats were exposed acutely to swim stress at 20, 25, 30, or 35°C for 15 min. Blood samples were obtained from each rat under basal conditions, at the end of the swim stress episode, and 15, 30, and 45 min after swim stress. Basal plasma levels of norepinephrine and epinephrine (EPI) were similar for 3- and 22-month-old rats. In contrast, plasma catecholamine responses of aged rats were significantly greater than those of young adult rats following swim stress at 20 and 25°C. Plasma catecholamine responses were similar for rats of the two ages following swim stress at 30 or 35°C. These findings indicate that aged rats have exaggerated sympathetic-adrenal medullary responses to acute swim stress at the lower water temperatures. Given the modulatory effects of plasma EPI on memory, these age-related alterations in plasma catecholamine responses to acute swim stress may influence spatial memory performance of rats in the Morris water maze.     

Spatial learning in pigs: effects of environmental enrichment and individual characteristics on behaviour and performance

This study investigated the effects of both environmental enrichment and individual behavioural characteristics on spatial cognitive capabilities of pigs, using a novel latent spatial learning paradigm based on Tolman’s detour experiments (1948). Pigs were housed either in ‘barren’ pens or in pens enriched with straw bedding from birth. Pigs were restrained in a Backtest at 10 and 17 days postpartum. Based on their escape behaviour in this test, which has been shown to reflect their behavioural style, six ‘high-resisting’(HR) and six ‘low-resisting’ (LR) pigs were selected from each housing environment (n = 24 in total). At 12 weeks of age, pairs of pen mates (LR and HR) were exposed to a maze three times (exploration trials). Pigs were then placed individually in the maze, and social reinstatement proved to be a strong incentive to find the exit leading to the home pen. We subsequently blocked the direct route to the exit, forcing animals to find a detour (memory test 1, MT1). This test was repeated once to investigate the relative improvement, i.e. detour learning (memory test 2, MT2). Housing condition and Backtest response strongly affected exploration patterns. In spite of this, no effects on performance during the subsequent memory tests were found. Performance was substantially improved in MT2, indicating that once a goal is apparent, pigs are able to solve a complex spatial memory task easily. In conclusion, social reinstatement provided a good incentive to complete a spatial task, and the substantial improvement in performance between MT1 and MT2 stresses the need for task complexity when testing spatial memory in pigs. Housing conditions or individual behavioural style did not affect spatial memory during MT1 or MT2. However, housing environment and behavioural style strongly affected explorative behaviour of pigs in an unfamiliar maze during both exploration trials and memory tests. This implicates that apparent effects of environmental enrichment on spatial learning and memory in pigs might reflect differences in explorative patterns rather than in cognitive processes.     

Sleep deprivation selectively impairs memory consolidation for contextual fear conditioning

Many behavioral and electrophysiological studies in animals and humans have suggested that sleep and circadian rhythms influence memory consolidation. In rodents, hippocampus-dependent memory may be particularly sensitive to sleep deprivation after training, as spatial memory in the Morris water maze is impaired by rapid eye movement sleep deprivation following training. Spatial learning in the Morris water maze, however, requires multiple training trials and performance, as measured by time to reach the hidden platform is influenced by not only spatial learning but also procedural learning. To determine if sleep is important for the consolidation of a single-trial, hippocampus-dependent task, we sleep deprived animals for 0–5 and 5–10 h after training for contextual and cued fear conditioning. We found that sleep deprivation from 0–5 h after training for this task impaired memory consolidation for contextual fear conditioning whereas sleep deprivation from 5–10 h after training had no effect. Sleep deprivation at either time point had no effect on cued fear conditioning, a hippocampus-independent task. Previous studies have determined that memory consolidation for fear conditioning is impaired when protein kinase A and protein synthesis inhibitors are administered at the same time as when sleep deprivation is effective, suggesting that sleep deprivation may act by modifying these molecular mechanisms of memory storage.     

Norepinephrine infused into the basolateral amygdala posttraining enhances retention in a spatial water maze task

Recent evidence indicates that the amygdala plays a role in modulating memory processes in other brain regions. For example, posttraining intra-amygdala infusions of amphetamine enhanced memory in both spatial and cued training water maze tasks; these tasks are known to depend on the integrity of the hippocampus and caudate nucleus, respectively. To determine whether this modulation is dependent on noradrenergic activation within a subregion of the amygdala (the basolateral nucleus), the present study examined the effects of posttraining microinfusions (0.2 microl) of norepinephrine or propranolol into the basolateral amygdala immediately following training in a spatial version of the water maze task. Rats received a four-trial training session on each of 2 consecutive days. On the third day, rats were given a 60-s probe test in the absence of a platform. Retention latencies obtained on the second training day revealed that norepinephrine dose-dependently enhanced retention for the location of the hidden platform. In contrast, propranolol significantly impaired retention. Probe trial analysis revealed that rats treated with 0.25 microg norepinephrine demonstrated a selective spatial bias for the training platform location relative to all other groups. These findings are consistent with others and support the view that the basolateral amygdala has a role in modulating memory storage by interacting with other brain regions.     

Rhesus monkeys (Macaca mulatta) adaptively monitor uncertainty while multi-tasking

As researchers explore animals’ capacity for metacognition and uncertainty monitoring, some paradigms allow the criticism that animal participants—who are always extensively trained in one stimulus domain within which they learn to avoid difficult trials—use task-specific strategies to avoid aversive stimuli instead of responding to a generalized state of uncertainty like that humans might use. We addressed this criticism with an uncertainty-monitoring task environment in which four different task domains were interleaved randomly trial by trial. Four of five macaques (Macaca mulatta) were able to make adaptive uncertainty responses while multi-tasking, suggesting the generality of the psychological signal that occasions these responses. The findings suggest that monkeys may have an uncertainty-monitoring capacity that is like that of humans in transcending task-specific cues and extending simultaneously to multiple domains.