Multiple spatial learning strategies in goldfish (Carassius auratus)

There is a considerable amount of evidence that mammals and birds can use different spatial learning strategies based on multiple learning and memory systems. Unfortunately, only a few studies have investigated spatial learning and memory mechanisms in other vertebrates. This study aimed to identify the strategies used by goldfish to solve two different spatial tasks in a series of three experiments. In experiment 1, two groups of goldfish (Carassius auratus) were trained either in a spatial constancy task (SC), in which visual cues signalled the goal indirectly, or in a directly cued task (DC) in which similar cues signalled the goal directly. Transfer tests were conducted to study the effects of discrete cue deletion on the performance in both tasks. In these transfer tests the performance of the animals trained in the DC task dropped to chance level when the cue that signalled the goal directly was removed. In contrast, the removal of any single cue did not disrupt SC performance. In experiment 2, fish trained in the SC or the DC task were trained with the goal reversed. Goldfish in the SC group needed fewer sessions to master the reversal task than DC animals. Finally, experiment 3 investigated the effects of a substantial modification of the geometrical features of the apparatus on the performance of animals trained in the SC or in the DC condition. The performance of DC goldfish was not affected, whereas the same change disrupted performance in the SC animals despite the presence of the visual cues. These results suggest that there are separate spatial learning and memory systems in fish. Whereas the DC animals used a typical guidance strategy, relying only on the cue that signalled the goal directly, SC fish relied on a strategy with the properties of an actual spatial mapping system. Thus, the comparative approach points to the generality of these learning strategies among vertebrates. Received: 10 October 1998 / Accepted after revision: 16 April 1999     

Interaction between locale and taxon strategies in human spatial learning

Three computer-based experiments which tested human participants in a non-immersive virtual watermaze task sought to determine factors which dictate whether the presence of a visual platform disrupts locale learning and taxon learning. In Experiment 1, the visible platform disrupted locale but not taxon learning based on viewpoint-independent and viewpoint-dependent information, respectively. In Experiment 2, taxon learning based on non-geometric cues providing viewpoint-dependent information was disrupted by the visible platform when the cues required relational information to disambiguate them from other cues. Experiment 3 placed participants in an isosceles triangular pool. The presence of the visible platform did not disrupt the encoding of relational information provided by shape of the pool. These results support the notion that geometric cues are encoded in a separate module which is impenetrable to non-geometric cues not creating the shape of the environment.     

Stress modulates the use of spatial versus stimulus-response learning strategies in humans

Animal studies provided evidence that stress modulates multiple memory systems, favoring caudate nucleus-based "habit" memory over hippocampus-based "cognitive" memory. However, effects of stress on learning strategy and memory consolidation were not differentiated. We specifically address the effects of psychosocial stress on the applied learning strategy in humans. We designed a spatial learning task that allowed differentiating spatial from stimulus-response learning strategies during acquisition. In 13 subsequent trials, participants (88 male and female students) had to locate a "win" card out of four placed at a fixed location in a 3D model of a room. Relocating one cue in the last trial allowed inferring the applied learning strategy. Half of them participated first in the "Trier Social Stress Test." Salivary cortisol and heart rate measurements were taken. Stressed participants used a stimulus-response strategy significantly more often than controls. Subsequent verbal report revealed that spatial learners had a more complete awareness of response options than stimulus-response learners. Importantly, learning performance was not affected by stress. Taken together, stress prior to learning facilitated simple stimulus-response learning strategies in humans-at the expense of a more cognitive learning strategy. Depending on the context, we consider this as an adaptive response.     

Impairment of spatial learning and hippocampal synaptic potentiation in c-kit mutant rats

The c-kit receptor tyrosine kinase encoded by the white-spotting (W) gene is highly expressed in rat hippocampal CA1–CA4 regions. We found an impaired spatial learning and memory in homozygous c-kit (Ws/Ws) mutant rats that have a 12-base deletion in the tyrosine kinase domain of the c-kit gene and a very low kinase activity. Electrophysiological studies in hippocampal slices revealed that the long-term potentiation (LTP) induced by the tetanic stimulation (100 Hz, 1 sec) in the mossy fiber (MF)–CA3 pathway, but not in the Schaffer collaterals/commissural–CA1 pathway, was significantly reduced in c-kit mutants compared with wild-type (+/+) rats. The paired-pulse facilitation (PPF) was measured before the tetanus and after the establishment of the LTP in each slice. The initial PPF in the MF–CA3 pathway positively correlated with the amplitude of the LTP in the wild-type rats but not in the c-kit mutant rats. Furthermore, they failed to show the normal characteristics observed in the MF–CA3 pathway of +/+ rats; that is, the negative correlation between the initial PPF and the changes in PPF measured after the LTP. These findings suggest an involvement of SCF/c-kit signaling in hippocampal synaptic potentiation and spatial learning and memory.     

Chronic stress modulates the use of spatial and stimulus-response learning strategies in mice and man

Acute stress modulates multiple memory systems in favor of caudate nucleus-dependent stimulus-response and at the expense of hippocampus-dependent spatial learning and memory. We examined in mice and humans whether chronic stress has similar consequences. Male C57BL/6J mice that had been repeatedly exposed to rats ("rat stress") used in a circular hole board task significantly more often a stimulus-response strategy (33%) than control mice (0%). While velocity was increased, differences in latency to exit hole, distance moved or number of holes visited were not observed. Increased velocity and performance during retention trials one day later indicates altered emotionality and motivation to explore in rat stressed mice. Forty healthy young men and women were split into "high chronic stress" and "low chronic stress" groups based on their answers in a chronic stress questionnaire ("Trier Inventory of Chronic Stress"-TICS) and trained in a 2D task. A test trial immediately after training revealed that participants of the "high chronic stress" group used the S-R strategy significantly more often (94%) than participants of the "low chronic stress" group (52%). Verbal self-reports confirmed the strategy derived from participants' choice in the test trial. Learning performance was unaffected by the chronic stress level. We conclude that one consequence of chronic stress is the shift to more rigid stimulus-response learning, that is accompanied by changes in motivational factors in mice.     

Reversible disconnection of the hippocampal-prelimbic cortical circuit impairs spatial learning but not passive avoidance learning in rats

Wistar rats, treated with the GABA(A) receptor agonist muscimol, were used to investigate the role of the hippocampal-prelimbic cortical (Hip-PLC) circuit in spatial learning in the Morris water maze task, and in passive avoidance learning in the step-through task. In the water maze task, animals were trained for three consecutive days and tested 24 h after the end of training. In the step-through task, the animals were trained once and tested 24h after training. On the training days, daily infusion of muscimol (0.5 microg/0.25 microl) was given (1) bilaterally to the ventral hippocampus (vHip), (2) bilaterally to the prelimbic cortex (PLC), (3) to the unilateral vHip and the ipsilateral PLC, or (4) for disconnecting the Hip-PLC circuit, to both the unilateral vHip and the contralateral PLC 30 min before training. The results showed that inhibition of the vHip resulted in disruption of performance in both tasks. Inhibition of the PLC produced impaired water maze performance, but had no effect on the step-through task. Disconnection of the Hip-PLC circuit produced similar effects to PLC inhibition. However, simultaneous inhibition of the unilateral vHip and the ipsilateral PLC had little effect on performance of the water maze task. The results suggested that spatial learning depends on the Hip-PLC circuit, whereas passive avoidance learning is independent of this circuit.     

Functional interaction of mGlu5 and NMDA receptors in aversive learning in rats

Metabotropic glutamate receptor 5 (mGlu5) has been implicated in a variety of learning processes and is important for inhibitory avoidance and conditioned taste aversion learning. MGlu5 receptors are physically connected with NMDA receptors and they interact with, and modulate, the function of one another in several brain regions. The present studies used systemic co-administration of an mGlu5 receptor positive allosteric modulator, 3-cyano-N-(1,3-diphenyl-1H-pyrazol-5-yl)benzamide (CDPPB) and an NMDA receptor antagonist dizocilpine maleate (MK-801) to characterize the interactions of these receptors in two aversive learning tasks. Male Sprague-Dawley rats were trained in a single-trial step-down inhibitory avoidance or conditioned taste aversion task. CDPPB (3 or 10mg/kg, s.c.), delivered by itself prior to the conditioning trial, did not have any effect on performance in either task 48 h after training. However, CDPPB (at 3mg/kg) attenuated the MK-801 (0.2mg/kg, i.p.) induced learning deficit in both tasks. CDPPB also reduced MK-801-induced hyperactivity. These results underlie the importance of mGlu5 and NMDA receptor interactions in modulating memory processing, and are consistent with findings showing the efficacy of positive allosteric modulators of mGlu5 receptors in reversing the negative effects of NMDA receptor antagonists on other behaviors such as stereotypy, sensorimotor gating, or working, spatial and recognition memory.     

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

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

Dietary restriction inhibits spatial learning ability and hippocampal cell proliferation in rats1

Abstract: We investigated the effect of dietary restriction on spatial learning ability and hippocampal cell proliferation in adult rats using two spatial learning tasks and immunohistochemical staining with 5‐bromo‐2′‐deoxyuridine (BrdU). Sixteen rats were divided into restricted or ad lib feeding groups at 70 days of age, and were trained in the delayed‐matching‐to‐place (DMTP) task (a working memory task) from 93 days of age, and then the Morris water maze task (a reference memory task). Dietary restriction had no effect on the DMTP task with 30 s delay and on the water maze task. However, in the DMTP task with 30 min delay, restricted rats performed significantly more poorly than ad lib rats. Quantitative analysis of hippocampal cell proliferation revealed that the density of newborn cells in restricted rats was significantly lower than that in ad lib rats. These results suggest that a loss of proliferating capacity in the hippocampus may be a candidate for an anatomical and biological basis for the cognitive decline caused by dietary restriction.     

Multiple systems for spatial learning: dead reckoning and beacon homing in rats

Rats homed with food in a large lighted arena. Without visual cues, they used dead reckoning. When a beacon indicated the home, rats could also use the beacon. Homing did not differ in 2 groups of rats, 1 provided with the beacon and 1 without it; tests without the beacon gave no evidence that beacon learning overshadowed dead reckoning (Experiment 1). When the beacon was at the home for 1 group and in random locations for another, there was again no evidence of cue competition (Experiment 2). Dead reckoning experience did not block acquisition of beacon homing (Experiment 3). Beacon learning and dead reckoning do not compete for predictive value but acquire information in parallel and are used hierarchically.     

Testosterone fails to reverse spatial memory decline in aged rats and impairs retention in young and middle-aged animals

Recently, the vasopressin (AVP) innervation in the rat brain was shown to be restored in senescent rats following long-term testosterone administration. In order to investigate whether this restoration is accompanied by an improvement in learning and memory, both sham- and testosterone-treated young (4.5 months), middle-aged (20 months), and aged (31 months) male Brown-Norway rats were tested in a Morris water maze. All animals learned to localize a cued platform equally well, indicating that the ability to learn this task was not affected by sensory, motoric, or motivational changes with aging or testosterone treatment. There were no significant differences in retention following cue training. Subsequent training with a hidden platform in the opposite quadrant of the pool (place training) revealed impaired spatial learning in middle-aged and aged animals. Retention following place training was significantly impaired in the sham-treated aged rats as compared with sham-treated young rats. Testosterone treatment did not improve spatial learning nor retention of spatial information, but, on the contrary, impaired retention in young and middle-aged animals. The present results confirm earlier reports on an impairment of spatial learning and memory in senescent rats but fail to support a role of decreased plasma testosterone levels and central AVP innervation in this respect.     

Patterns of brain acetylcholine release predict individual differences in preferred learning strategies in rats

Acetylcholine release was measured simultaneously in the hippocampus and dorsal striatum of rats before and during training on a maze that could be learned using either a hippocampus-dependent spatial strategy or a dorsal striatum-dependent turning strategy. A probe trial administered after rats reached a criterion of 9/10 correct responses revealed that about half of the rats used a spatial strategy and half a turning strategy to solve the task. Acetylcholine release in the hippocampus, as well as the ratio of acetylcholine release in the hippocampus vs. the dorsal striatum, measured either before or during training, predicted these individual differences in strategy selection during learning. These findings suggest that differences in release of acetylcholine across brain areas may provide a neurobiological marker of individual differences in selection of the strategies rats use to solve a learning task.     

Chronic, severe hypertension does not impair spatial learning and memory in Sprague-Dawley rats

This study tested the hypothesis that long-term hypertension impairs spatial learning and memory in rats. In 6-wk-old Sprague-Dawley rats, chronic hypertension was induced by placing one of three sizes of stainless steel clips around the descending aorta (above the renal artery), resulting in a 20–80-mm Hg increase of arterial pressure in all arteries above the clip, that is, the upper trunk and head. Ten months later, the rats were tested for 5 d in a repeated-acquisition water maze task, and on the fifth day, they were tested in a probe trial; that is, there was no escape platform present. At the end of the testing period, the nonsurgical and sham control groups had similar final escape latencies (16±4 sec and 23±9 sec, respectively) that were not significantly different from those of the three hypertensive groups. Rats with mild hypertension (140–160 mm Hg) had a final escape latency of 25±6 sec, whereas severely hypertensive rats (170–199 mm Hg) had a final escape latency of 21±7 sec and extremely hypertensive rats (>200 Hg) had a final escape latency of 19±5 sec. All five groups also displayed a similar preference for the correct quadrant in the probe trial. Together, these data suggest that sustained, severe hypertension for over 10 mo is not sufficient to impair spatial learning and memory deficits in otherwise normal rats.     

Changes in cytochrome oxidase activity following spatial working memory learning in rats treated with tacrine

We evaluated change in cytochrome oxidase (COx) activity of the hippocampus and related structures of the limbic system following spatial working memory learning in rats after treatment with tacrine (8.0mg/kg). Control groups treated with saline and tacrine and an untreated group were added. Acetylcholinesterase optical density levels were also measured. The tacrine and saline groups showed similar behavioral results, but a decrease in COx activity was found in the tacrine group in the prefrontal cortex, nucleus accumbens, anterior thalamus, hippocampus and nucleus basalis of Meynert. Similarly, acetylcholinesterase levels of the tacrine group were lower in most of the regions. Learning-related increase in COx activity was found in the prefrontal cortex and dentate gyrus in the saline group. The tacrine group presented the same increase in the anterodorsal thalamus, dentate gyrus, CA3 and mammillary nuclei. These results suggest that inhibition of the acetylcholinesterase produces a different pattern of learning-related neuronal activity in the limbic system of the rat.     

Choice strategies in multiple-cue probability learning

Choice strategies for selecting among outcomes in multiple-cue probability learning were investigated using a simulated medical diagnosis task. Expected choice probabilities (the proportion of times each outcome was selected given each cue pattern) under alternative choice strategies were constructed from corresponding observed judged probabilities (of each outcome given each cue pattern) and compared with observed choice probabilities. Most of the participants were inferred to have responded by using a deterministic strategy, in which the outcome with the higher judged probability is consistently chosen, rather than a probabilistic strategy, in which an outcome is chosen with a probability equal to its judged probability. Extended practice in the learning environment did not affect choice strategy selection, contrary to reports from previous studies, results of which may instead be attributable to changes with practice in the variability and extremity of the perceived probabilities on which the choices were based.     

The effects of spatial configuration on preschoolers' attention strategies,selective attention,and incidental learning

This study investigated the effects of spatial arrangement on preschool children's selective attention and incidental learning. Three‐ and four‐year old children were shown a multi‐coloured box designated as a ‘special place’ containing miniature chairs and models of animals. One category of objects were designated as relevant and one as irrelevant. Relevant items were placed in each of the apparatus' corners, in the middle of its walls, or in two corners and in the middle of two walls. Findings revealed that children shown relevant items in corners demonstrated the greatest number of correct relocations for relevant items while those shown relevant items in the middle of the walls showed the greatest number of correct relocations for irrelevant items. Findings also suggest that for both age groups, the ability to recall relevant items may have been independent of their ability to demonstrate a selective attention strategy. Copyright © 2005 John Wiley & Sons, Ltd.     

Rats acquire spatial learning sets

This experiment was designed to examine the development of a spatial learning set in rats and some of the variables influencing the retention of individual problems. The apparatus was a plus maze. At the beginning of each test, the rat was put on two arms, each in a different place. Food was present in one of the arms, but not in the other. The rat was then given a choice between these two places; the correct response was to return to the place that previously contained food (win-stay, lose-shift, response-reinforcement contingency). Fifty different two-choice spatial discriminations were given, each in a different location. At the end of testing, the mean percentage of correct responding for the first choice between the two places was 83%. Control procedures showed that the discriminative stimuli were distal, extramaze spatial stimuli. Variations of the procedure examined the influence of proactive interference and temporal delay on the memory for each discrimination. These results demonstrate that rats can develop a spatial learning set and provide new information about the characteristics of the memory underlying learning sets.     

Prolonged inactivation of the hippocampus reveals temporally graded retrograde amnesia for unreinforced spatial learning in rats

We investigated whether systems consolidation of spatial memory could be detected in a non-navigational, spatial-learning test that takes advantage of rats’ natural propensity to preferentially investigate an object that was displaced relative to spatial cues more than an object that remained stationary. Previous studies using navigational spatial-learning tests have generally failed to reveal temporally-graded retrograde amnesia, possibly because the hippocampus needs to be intact for the retrieval and/or processing of navigational information during the test. In the present study, the hippocampus of rats was kept inactivated, at two sites along its septo-temporal axis (dorsal and intermediate), for four consecutive days, beginning either 3 h or 5 days after familiarization to two identical objects in an open field. Rats that had their hippocampus inactivated beginning 5 days but not 3 h after familiarization showed evidence that they remembered the previous location of the displaced object. The results suggest that systems consolidation of spatial memories can be detected using a non-navigational test of spatial memory.     

Estrogens and progestins enhance spatial learning of intact and ovariectomized rats in the object placement task

Steroid modulation of cognitive function has focused on estrogen (E(2)), but progestins naturally co-vary with E(2) and may also influence cognitive performance. Spatial performance in the object placement task over endogenous hormonal states in which E(2) and progestins vary, and when E(2) and/or progestins were administered, was examined. Experiment 1: Rats in proestrus or estrus had significantly better performance in the object placement task than did diestrus rats. Experiment 2: Rats in the third trimester, post-partum, or lactation exhibited significantly better performance in the object placement task than did rats in the first trimester. Experiment 3: Ovariectomized (ovx) rats administered 17beta-estradiol (0.9 mg/kg), subcutaneously (sc), progesterone (P; 4 mg/kg, sc), or E(2) and P, immediately after training in the object placement task, performed significantly better when tested 4h later, than did control rats administered vehicle (sesame oil 0.2 cc). Experiment 4: ovx rats administered E(2) or P with a 1.5h delay after training in the object placement task, did not perform differently than vehicle-administered controls. Experiment 5: ovx rats administered post-training E(2), which has a high affinity for both E(2) receptor (ER)alpha and beta isoforms, or propyl pyrazole triol (PPT; 0.9 mg/kg, sc), which is more selective for ERalpha than ERbeta, had significantly better performance in the object placement task than did rats administered vehicle or diarylpropionitrile (DPN; 0.9 mg/kg, sc), an ERbeta selective ligand. Experiment 6: ovx rats administered P, or its metabolite, 5alpha-pregnan-3alpha-ol-20-one (3alpha,5alpha-THP; 4 mg/kg, sc), immediately post-training performed significantly better in the object placement task than did vehicle control rats. Thus, performance in the object placement task is better when E(2) and/or P are naturally elevated or when E(2), the ERalpha selective ER modulator PPT, P, or its metabolite, 3alpha,5alpha-THP, are administered post-training.