Strategy selection in a task with spatial and nonspatial components: effects of fimbria-fornix lesions in rats.

The main purpose of the present research was to investigate the ability of rats to learn a 12-arm radial maze task that requires the concurrent utilization of both spatial and intramaze cue information. The task involves in a single trial both place and cue learning as well as reference memory (RM) and working memory (WM). Since the animal can choose place and cue arms in any order, the strategies employed to learn the task can be studied as well as the kinds of memory errors that are made. The results of Experiment 1 showed that the number of errors made on the place and cue components of the task did not differ, and that more RM than WM errors were made early during learning. As the task was learned, the animals tended to choose the place arms before choosing the intramaze cue arms, thus suggesting that a spatial strategy was employed first followed by a cue strategy. In Experiment 2 lesions of the fimbria-fornix resulted in temporary impairments in both RM and WM that were especially apparent on the spatial component of the task. The lesioned rats also switched from choosing mostly place arms early during the trial to choosing more cue arms. While fimbria-fornix lesioned rats recovered from the memory impairments with training, the change in response strategy persisted throughout postoperative testing. The procedure of combining both spatial and non-spatial components concurrently in the same task should prove of value in studying response strategies in animals.     

Learning strategy selection in the water maze and hippocampal CREB phosphorylation differ in two inbred strains of mice

Learning strategy selection was assessed in two different inbred strains of mice, C57BL/6 and DBA/2, which are used for developing genetically modified mouse models. Male mice received a training protocol in a water maze using alternating blocks of visible and hidden platform trials, during which mice escaped to a single location. After training, mice were required to choose between the spatial location where the platform had been during training (a place strategy) and a visible platform presented in a new location (a cued/response strategy). Both strains of mice had similar escape performance on the visible and hidden platform trials during training. However, in the strategy preference test, C57BL/6 mice selected a place strategy significantly more often than DBA/2 mice. Because much evidence implicates the hippocampus and striatum as important neural substrates for spatial/place and cued/response learning, respectively, the engagement of the hippocampus was then assessed after either place or cue training by determining levels of cAMP response element-binding protein (CREB) and phosphorylated CREB (pCREB) in these two mouse strains. Results revealed that hippocampal CREB levels in both strains of mice were significantly increased after place in comparison to cued training. However, the relation of hippocampal pCREB levels to training was strain dependent; pCREB was significantly higher in C57BL/6 mice than in DBA/2 mice after place training, while hippocampal pCREB levels did not differ between strains after cued training. These findings indicate that pCREB, specifically associated with place/spatial training, is closely tied to differences in spatial/place strategy preference between C57BL/6 and DBA/2 mice.     

Orientation in the cuttlefish <Emphasis Type="Italic">Sepia officinalis</Emphasis>: response <Emphasis Type="Italic">versus</Emphasis> place learning

Several studies have demonstrated that mammals, birds and fish use comparable spatial learning strategies. Unfortunately, except in insects, few studies have investigated spatial learning mechanisms in invertebrates. Our study aimed to identify the strategies used by cuttlefish (Sepia officinalis) to solve a spatial task commonly used with vertebrates. A new spatial learning procedure using a T-maze was designed. In this maze, the cuttlefish learned how to enter a dark and sandy compartment. A preliminary test confirmed that individual cuttlefish showed an untrained side-turning preference (preference for turning right or left) in the T-maze. This preference could be reliably detected in a single probe trial. In the following two experiments, each individual was trained to enter the compartment opposite to its side-turning preference. In Experiment 1, distal visual cues were provided around the maze. In Experiment 2, the T-maze was surrounded by curtains and two proximal visual cues were provided above the apparatus. In both experiments, after acquisition, strategies used by cuttlefish to orient in the T-maze were tested by creating a conflict between the formerly rewarded algorithmic behaviour (turn, response learning) and the visual cues identifying the goal (place learning). Most cuttlefish relied on response learning in Experiment 1; the two strategies were used equally often in Experiment 2. In these experiments, the salience of cues provided during the experiment determined whether cuttlefish used response or place learning to solve this spatial task. Our study demonstrates for the first time the presence of multiple spatial strategies in cuttlefish that appear to closely parallel those described in vertebrates.     

An assessment of response, direction and place learning by rats in a water T-maze

Behavioral data suggest that distinguishable orientations may be necessary for place learning even when distal cues define different start points in the room and a unique goal location. We examined whether changes in orientation are also important in place learning and navigation in a water T-maze. In Experiment 1, rats were trained to locate a hidden platform and given a no-platform probe trial after 16 and 64 trials with the maze moved to a new position. Direction and response strategies were more prevalent than a place strategy. In Experiment 2, acquisition of place, response and direction strategies was assessed in a water T-maze that was moved between two locations during training. Rats were impaired on the place task when the maze was translated (moved to the L or R) but were successful when the maze was rotated across trials. These data are consistent with findings from appetitive tasks.     

Adult blood pressure reduction in spontaneously hypertensive rats reared by normotensive Sprague-Dawley mothers.

Spontaneously hypertensive (SHR), Wistar-Kyoto (WKY) normotensive, and Sprague-Dawley (SD) normotensive rats were either reared by their natural mothers (controls) or fostered to a mother of one of the other strains. The effects of rearing environment were assessed by measures of body weight at weaning and adult resting mean arterial blood pressure (MAP) and heart rate (HR). At weaning, SHR control rats weighed less than WKY controls which in turn weighed less than SD controls. SHR and WKY rats reared by SD mothers weighed significantly more than their respective controls, whereas SD rats reared by either SHR or WKY mothers weighed less than SD control rats. Manipulation of the maternal environment was attended by a change in adult resting MAP in only one group. SHR rats reared by SD mothers had MAPs which were significantly lower than SHRs reared by their natural mothers. No within-strain adult HR differences were observed between control and cross-fostered groups. These data indicate that the effects of cross-fostering on adult resting MAP previously reported for SHR and WKY animals are generalizable to another normotensive strain. That is, genetically hypertensive (SHR) animals exposed to a normotensive (WKY or SD) maternal environment display a reduction in adult resting MAP, whereas hypertension or an increase in adult MAP is not induced in normotensive rats (WKY or SD) as a consequence of exposure to a hypertensive maternal environment.     

Emergence of a cue strategy preference on the water maze task in aged C57B6 x SJL F1 hybrid mice

The effects of age on cue learning, spatial reference memory, and strategy preference were assessed in B6 × SJL F1 mice by using the Morris water maze. This mouse strain is of particular interest because it is the background strain for a common transgenic model of Alzheimer's disease, the Tg2576 mouse, which develops plaques and other neurobiological markers of pathology beginning at 8 mo and increasing in severity with advanced age. In the current study, 12- and 23-mo-old C57B6 × SJL F1 mice were serially trained in cue and place versions of the Morris water maze task. At the completion of training, mice received a strategy probe test in which place (hidden) and cue (visible) strategies were in competition. Cue and spatial learning ability was maintained between 12 and 23 mo of age; however, on the strategy preference probe test, the 23-mo-old mice exhibited a significant bias toward the selection of a cue strategy. There was no relationship between strategy preference in the probe test and spatial learning ability, but the 23-mo-old mice did exhibit a strong trend toward shorter latencies during visible platform training, possibly reflecting the enhanced function of striatal-based neural systems in aging. These data demonstrate that 23-mo-old C57B6 × SJL F1 mice are capable of effective place learning, but if a place strategy is pitted against the use of a cue strategy, the use of a cue strategy predominates in the aged mice. The strategy preference observed here may reflect an emergence of differential processing in underlying brain circuitry with age in the B6 × SJL F1 mouse strain.     

Spatial learning in a T-maze by the crayfish Orconectes rusticus

The T-maze has commonly been used to investigate the mechanisms underlying spatial learning in vertebrates and has yielded much information about how animals use response and place cues to orient toward a goal. We designed a T-maze to study the spatial learning abilities of crayfish (Orconectes rusticus), using tactile stimuli as a place cue and escape from warm water for reinforcement. An initial experiment found that most animals did not display a side-turning bias when first placed in the maze, and hence animals were randomly assigned to escape from the left or the right arm, one of which contained a smooth floor and the other a rough floor. We found that, over repeated trials, the latency to escape and the number of turns made prior to escaping significantly decreased indicating that crayfish learned to escape from the maze more rapidly and efficiently. Learning occurred over the course of six trials on a single day, and over 5 days of testing, providing evidence for spatial memory lasting 24 hr. In probe trials, in which experienced animals started the maze in an arm opposite to that used during training trials, crayfish did not display a preference for either response-based learning or place-based learning. Instead they engaged in renewed exploration of the entire maze. These findings suggest that, in addition to remembering the location of the exit, crayfish also remembered the overall configuration of the maze.     

Combined uridine and choline administration improves cognitive deficits in spontaneously hypertensive rats

Rationale. Hypertension is considered a risk factor for the development of cognitive disorders, because of its negative effects on cerebral vasculature and blood flow. Genetically induced hypertension in rats has been associated with a range of cognitive impairments. Therefore, spontaneously hypertensive rats (SHR) can potentially be used as a model for cognitive deficits in human subjects. Consecutively, it can be determined whether certain food components can improve cognition in these rats. Objective. The present study aimed to determine whether SHR display specific deficits in attention, learning, and memory function. Additionally, effects of chronic uridine and choline administration were studied. Methods. 5-7 months old SHR were compared with normotensive Wistar-Kyoto (WKY) and Sprague-Dawley (SD) rats. (a) The operant delayed non-matching-to-position (DNMTP) test was used to study short-term memory function. (b) The five-choice serial reaction time (5-CSRT) task was used to assess selective visual attention processes. (c) Finally, the Morris water maze (MWM) acquisition was used as a measure for spatial learning and mnemonic capabilities. Results. (1) SHR exhibited significantly impaired performance in the 5-CSRT test in comparison with the two other rat strains. Both the SHR and WKY showed deficits in spatial learning when compared with the SD rats. (2) Uridine and choline supplementation normalized performance of SHR in the 5-CSRT test. (3) In addition, uridine and choline treatment improved MWM acquisition in both WKY and SHR rats. Conclusion. The present results show that the SHR have a deficiency in visual selective attention and spatial learning. Therefore, the SHR may provide an interesting model in the screening of substances with therapeutic potential for treatment of cognitive disorders. A combination of uridine and choline administration improved selective attention and spatial learning in SHR.     

Development of spatial memory and spatial orientation in preschoolers and primary school children

The present study addresses the question of what kind of information children use when orientating in new environments, if given proximal and distal landmarks, and how spatial memory develops in the investigated age groups. Ten 5-year-old, ten 7-year-old and ten 10-year-old children were presented with the ‘Kiel Locomotor Maze’, containing features of the Radial Arm Maze and the Morris Water Maze, in order to assess spatial memory and orientation. Children had to learn to approach baited locations only. Task difficulty was equated with respect to the children's age. Training was given until the children reached criterion. During testing, the maze configuration and response requirements were systematically altered, including response rotation, cue rotation, cue deletion and response rotation with cue deletion in order to assess the spatial strategies used by the children. During training and testing, working-memory errors (WM), reference-memory errors (RM) and working-reference memory errors (WR) were recorded. As expected, no difference between age groups appeared during training, thus confirming comparable task difficulty across age groups. During testing, age groups differed significantly with regard to the orientation strategy used. The 5-year-olds were bound to a cue strategy, orientating towards local, proximal cues. The 10-year-olds mastered all tasks, thus displaying a place strategy, being able to use distal cues for orientation, and were even able to do so after being rotated 180°. The 7-year-olds proved to be at an age of transition: five of them were bound to a cue strategy, five children were able to adopt a place strategy. The differences in the orientation strategies used by children of different age groups was reflected by the sum of errors they made, also by RM. WM were found to be rare, especially in older children. We conclude that preschoolers use a cue strategy, that the development of place strategies occurs during primary school age and seems to be complete by the age of 10 years.     

Complementary roles for the amygdala and hippocampus during different phases of appetitive information processing

Evidence collected from rodent models of memory storage suggests that rapid forms of learning engage the involvement of multiple brain regions each of which may participate in a different component of information processing. The present study used temporary inactivation of the amygdala and hippocampus during different phases of information processing on a one-trial appetitive-conditioning task to examine how these two regions might participate in the storage of appetitive memories. Male Long Evans rats were chronically implanted into the amygdala or dorsal hippocampus and food deprived. Rats were trained on a radial maze conditioned cue preference task where training occurred in one 40-min session and testing took place 24 h later. The amygdala or hippocampus was inactivated separately with muscimol (50 ng/microl) injected immediately before or after training, or immediately before testing. Saline-injected rats displayed a conditioned preference by spending more time in the arm that previously contained food than in the arm that did not contain food. Muscimol injected into the amygdala before training or testing blocked the conditioned preference. Muscimol injected into the hippocampus immediately after training blocked the conditioned preference. These results suggest that the processing of memories may require multiple contributions from separate brain systems for at least short-term (24 h) storage. The resulting output from each system may converge on a similar downstream target to influence behavior.     

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.     

Test for effects of visual and position cues on T-maze learning in toads

This research was concerned with the effects of different classes of cues on the ability of toads (Bufo marinus) to learn an escape task, discrimination learning, in a T-maze. The cues were either a black or white brightness cue, a right or left position cue, or combinations of brightness and position cues. The toads were given a .6-A shock until they made the correct response. Results suggested that toads are capable of learning a discrimination task based on either a position or brightness cue. However, the rate of learning was influenced by strong aversion to the white arm when escaping from an aversive stimulus. No particular preference for either brightness or position cues was found independent of this aversion.     

Bonobos, chimpanzees, gorillas, and orang utans use feature and spatial cues in two spatial memory tasks

Animals commonly use feature and spatial strategies when remembering places of interest such as food sources or hiding places. We conducted three experiments with great apes to investigate strategy preferences and factors that may shape them. In the first experiment, we trained 17 apes to remember 12 different food locations on the floor of their sleeping room. The 12 food locations were associated with one feature cue, so that feature and spatial cues were confounded. In a single test session, we brought the cues into conflict and found that apes, irrespective of species, showed a preference for a feature strategy. In the second experiment, we used a similar procedure and trained 25 apes to remember one food location on a platform in front of them. On average, apes preferred to use a feature strategy but some individuals relied on a spatial strategy. In the final experiment, we investigated whether training might influence strategy preferences. We tested 21 apes in the platform set-up and found that apes used both, feature and spatial strategies irrespective of training. We conclude that apes can use feature and spatial strategies to remember the location of hidden food items, but that task demands (e.g. different numbers of search locations) can influence strategy preferences. We found no evidence, however, for the role of training in shaping these preferences.     

Auditory startle in normotensive and hypertensive rats

In the present experiment auditory startle was examined in male and female rats of the spontaneously hypertensive (SHR) and Wistar-Kyoto normotensive (WKY) strains and borderline hypertensive rats (BHR) derived from cross-breeding SHR females with WKY males. The magnitude of auditory startle declined over trials and was significantly higher in WKYs than in both SHRs and BHRs which did not differ from each other. These data add to an increasing body of literature concerning behavioral differences between hypertensive and normotensive rats and are discussed as they relate to the possible strain differences in either behavioral reactivity or tonic fear.     

Glucose injections into the dorsal hippocampus or dorsolateral striatum of rats prior to T-maze training: modulation of learning rates and strategy selection

The present experiments examined the effects of injecting glucose into the dorsal hippocampus or dorsolateral striatum on learning rates and on strategy selection in rats trained on a T-maze that can be solved by using either a hippocampus-sensitive place or striatum-sensitive response strategy. Percentage strategy selection on a probe trial (P(crit)) administered after rats achieved criterion (nine of 10 correct choices) varied by group. All groups predominately exhibited a response strategy on a probe trial administered after overtraining, i.e., after 90 trials. In experiment 1, rats that received intrahippocampal glucose injections showed enhanced acquisition of the T-maze and showed increased use of response solutions at P(crit) compared with that of unimplanted and artificial cerebral spinal fluid (aCSF)-treated groups. These findings suggest that glucose enhanced hippocampal functions to accelerate the rate of learning and the early adoption of a response strategy. In experiment 2, rats that received intrastriatal glucose injections exhibited place solutions early in training and reached criterion more slowly than did aCSF controls, with learning rates comparable to those of unoperated and operated-uninjected controls. Relative to unoperated, operated-uninjected and glucose-injected rats, rats that received intrastriatal aCSF injections showed enhanced acquisition of the T-maze and increased use of response solutions at P(crit). The unexpected enhanced acquisition seen after striatal aCSF injections suggests at least two possible interpretations: (1) aCSF impaired striatal function, thereby releasing competition with the hippocampus and ceding control over learning to the hippocampus during early training trials; and (2) aCSF enhanced striatal functioning to facilitate striatal-sensitive learning. With either interpretation, the results indicate that intrastriatal glucose injections compensated for the aCSF-induced effect. Finally, enhanced acquisition regardless of treatment was accompanied by rapid adoption of a response solution for the T-maze.     

Intrahippocampal muscimol shifts learning strategy in gonadally intact young adult female rats

Learning strategy preferences depend upon circulating estrogen levels, with enhanced hippocampus-sensitive place learning coinciding with elevated estrogen levels. The effects of estrogen on strategy may be mediated by fluctuations in GABAergic function, given that inhibitory tone in the hippocampus is low when estrogen is high. We investigated the effects on learning strategy of intrahippocampal injections of a GABA(A) agonist in gonadally intact female rats. On the day of training, rats received 0.3 microL intrahippocampal infusions of muscimol (0.26 nmol or 2.6 nmol) or saline 20 min prior to training on a T-maze in which place (hippocampus-sensitive) or response (striatum-sensitive) strategies offer effective solutions. Muscimol treatment increased the use of the response strategy in a dose-dependent manner without influencing learning speed, indicating that muscimol modulated strategy and not learning ability. Furthermore, the muscimol-related shift to response strategies varied across the estrous cycle. The results indicate that increasing inhibition in the hippocampus biases rats away from hippocampus-sensitive place learning strategies and toward hippocampus-insensitive response learning strategies without a learning deficit. Furthermore, rats at proestrus demonstrated the most dramatic shift in learning strategy following muscimol treatment compared with control conditions, while rats at estrus demonstrated the most complete bias toward response strategies. The enhanced use of hippocampus-sensitive strategies at proestrus likely results from reduced hippocampal inhibition.     

Passive-avoidance behavior of spontaneously hypertensive rats

Spontaneously hypertensive rate (SHR) generally exhibit higher performance in avoidance tasks than Wistar-Kyoto control rats (WKY) do. The SHR are more active than the WKY after transfer to a novel environment and after electric footshocks. The present study examined the performance, behavior, and plasma corticosterone of young male SHR and WKY in a passive-avoidance task in which high levels of locomotor activity do not facilitate performance. The effects of three levels of discriminability of the safe area were studied. Passive-avoidance performance was statistically significantly lower in the SHR, but the difference was small. There was no difference between the SHR and the WKY in post-test plasma-corticosterone levels, and there was no relationship between ambulation and plasma-corticosterone levels. The behavioral differences between the SHR and the WKY varied as a function of the discriminability of the safe area. Specifically, in the low-discriminability condition, ambulation, but not rearings, was equally suppressed in the SHR as in the WKY and there was no difference in immobility. In the high-discriminability condition the SHR exhibited more ambulation, more rearing, and less immobility than the WKY. These data confirm that the SHR exhibit an increased tendency for facilitation of locomotor activity during activation compared to the WKY. Because the passive-avoidance performance of the SHR was lower than that of the WKY, these data suggest that previous reports of superior avoidance learning in the SHR reflect their elevated level of locomotor activity rather than an improved ability to acquire conditioned responses. Ability to discriminate stimuli seems to be normal in the SHR since ambulation was modified according to stimulus parameters.     

Tiger salamanders’ (<Emphasis Type="Italic">Ambystoma tigrinum</Emphasis>) response learning and usage of visual cues

We explored tiger salamanders’ (Ambystoma tigrinum) learning to execute a response within a maze as proximal visual cue conditions varied. In Experiment 1, salamanders learned to turn consistently in a T-maze for reinforcement before the maze was rotated. All learned the initial task and executed the trained turn during test, suggesting that they learned to demonstrate the reinforced response during training and continued to perform it during test. In a second experiment utilizing a similar procedure, two visual cues were placed consistently at the maze junction. Salamanders were reinforced for turning towards one cue. Cue placement was reversed during test. All learned the initial task, but executed the trained turn rather than turning towards the visual cue during test, evidencing response learning. In Experiment 3, we investigated whether a compound visual cue could control salamanders’ behaviour when it was the only cue predictive of reinforcement in a cross-maze by varying start position and cue placement. All learned to turn in the direction indicated by the compound visual cue, indicating that visual cues can come to control their behaviour. Following training, testing revealed that salamanders attended to stimuli foreground over background features. Overall, these results suggest that salamanders learn to execute responses over learning to use visual cues but can use visual cues if required. Our success with this paradigm offers the potential in future studies to explore salamanders’ cognition further, as well as to shed light on how features of the tiger salamanders’ life history (e.g. hibernation and metamorphosis) impact cognition.     

Open-field behavior in two models of genetic hypertension and the behavioral effects of salt excess

In order to assess the relationship of behavior to blood pressure and salt intake, open-field behavior was studied in 123 rats of the spontaneously hypertensive (SHR), Wistar-Kyoto (WKY), Sprague-Dawley (SD), and Dahl resistant (DR) and sensitive (DS) strains. DS rats become hypertensive upon exposure to either high dietary salt or psychogenic stress, while DR rats remain normotensive. A circular photobeam open field was used under full room illumination. Three 5-min trials were given on consecutive days. Rats were tested with or without 5 days of an 8% NaCl diet. We found that DS rats were less active than DR rats, regardless of diet. In contrast, SHR rats were more active than WKY rats. However, DS and SHR rats were equally active. Thus, behavioral differences between these two models of hypertension are expressed by the normotensive control strains. The relative ranking of activity levels between strains was DR = SD greater than SHR = DS greater than WKY. High-salt-enhanced intertrial habituation, defined as the decrease in activity across trials (DS, 100%; SD, 82%; SHR, 90%; WKY, 1350%; but DR, -50%) as well as intratrial habituation, defined as the decrease from the first to the second half of the trial (14%, all subjects). Defecation was increased with high salt (DS, 975%; SD, 59%; SHR, 267%; WKY, 89%; but DR, 40%). These effects of high salt may reflect an increase in an emotionality factor. DR rats were largely resistant to the behavioral effects of salt. Total activity was positively correlated with blood pressure in hypertensive rats, r(42) = 0.33, p less than .01, but negatively correlated in normotensive rats, r(81) = -0.34, p less than .01. The proportion of total activity occurring in the first half of the trial for the initial test day was correlated with blood pressure in normotensive rats r(81) = 0.44, p less than .01. Dietary salt excess has behavioral as well as cardiovascular consequences.     

Training method dramatically affects the acquisition of a place response in rats with neurotoxic lesions of the hippocampus.

A considerable number of studies have demonstrated that hippocampal damage impairs the acquisition of a place response in rats. In Experiment 1, using a four-arm plus-shaped maze, we replicated this finding. Experiment 2 showed, however, that hippocampally damaged rats can learn a place response just as well as control rats when, during the training, a salient intramaze landmark indicates the position of the goal (the west arm). After reaching criterion, the hippocampal and control groups performed the task with the same degree of mastery during a transfer test in which the intramaze signal used during the acquisition was removed. In Experiment 3, the intramaze cue was substituted by an egocentric cue. The results revealed that both control and lesioned subjects learned the spatial problem well. However, a transfer test showed that control rats learned the task using a place response strategy but hippocampally lesioned animals used a rigid, hyperspecific strategy. Taken together, these results suggest that special training procedures which encourage variability in response versus perseveration make it possible to overcome the acquisition deficit normally observed in hippocampal rats.