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PubMed2003

Massed but not spaced training impairs spatial memory.

The Morris water maze and the object displacement task are two popular tools used to investigate spatial learning and memory. Research has focused mainly on the acquisition of spatial tasks while little attention has been given to the retention phase. We examined the effects of different training procedures on retention of the water maze and also reactivity to spatial change in the object displacement task 7 days post-acquisition. We found that massed-trained animals were impaired on retention of the water maze compared to those animals that had received spaced-training. We also found that the massed-trained animals habituated readily to their environment in the object displacement task while the spaced-trained group did not. Furthermore the massed-trained group did not react to spatial change 7 days post-habituation compared to the increased reactivity displayed by the spaced-trained group. Results are discussed in terms of poor encoding of the environment leading to poor retention.

Analysis of Variance↗

PubMed1995

Spatial- and locomotion-related neural representation in rat hippocampus following long-term survival from ischemia.

Spatial and locomotion-related behavioral correlates of hippocampal cell discharge were compared between ischemic and sham-control rats performing a spatial maze. Ischemic rats showed impaired choice accuracy during maze acquisition, but not during asymptote performance. Single-unit correlates during asymptote performance revealed enhanced spatial selectivity of CA2/3 complex-spike cells coincident with attenuated place-specific firing by hilar complex-spike or subicular cells. Responsivity to locomotion state by stratum granulosum interneurons was exaggerated, and locomotion-induced changes in firing of hilar and subicular interneurons was reduced. Ischemic rats showed recovered spatial learning abilities as evidenced by the fact that acquisition of the spatial task in a second environment was not impaired. Because representational reorganization was also observed in ischemic, maze-naive rats, brain injury per se appears to change information coding schemes.

Animals↗

PubMedDate not supplied

The effects of telencephalic pallial lesions on spatial, temporal, and emotional learning in goldfish.

In mammals, the pallial amygdala is implicated in emotional learning and memory, whereas the hippocampus is involved in spatial, contextual, or relational memory. This review presents a set of experiments aimed to study the involvement of the dorsomedial and dorsolateral telencephalon of goldfish in spatial and active avoidance learning. Results showed that (1) medial lesions impaired both acquisition and retention of conditioned avoidance response in two-way active avoidance learning experiments with stimuli overlapping (emotional factor) and with an interstimuli gap (temporal and emotional factors), and (2) the medial lesion did not affect spatial learning (spatial, contextual, or relational factors). In contrast, lateral lesions did not impair conditioned avoidance response with stimuli overlapping, but affected conditioned avoidance response with an interstimuli gap and spatial learning. These results support the presence of two differentiated memory systems in teleost fish based on discrete pallial regions: emotional (dorsomedial telencephalon) and spatial/temporal or relational (dorsolateral telencephalon). Furthermore, these functional data support the homology between the medial pallium of the teleost and the pallial amygdala of land vertebrates, and between the teleost lateral pallium and the mammalian hippocampus.

Amygdala↗

PubMed1997

The time course of spatial and object learning in Parkinson's disease.

Parkinson's disease (PD) is characterized by spatial memory dysfunction, but the selectivity of the deficit remains unclear. We addressed this issue by comparing performance on spatial and object variants of a conditional associative learning task, and by analysing the data with time series analytical techniques. The 11 PD subjects and 15 normal control subjects learned stimulus-stimulus pairings through trial-and-error learning. PD subjects were selectively impaired on the spatial condition: they required more trials to achieve criterion, learned at a slower rate and displayed a working memory deficit. The groups did not differ in the object condition. These results suggest a distinction between material-specific spatial and object visual memory systems. Further, they indicate that spatial learning and memory are selectively impaired in early PD, suggesting that interactions between the basal ganglia and prefrontal cortex are important for the mediation of high-level cognition.

Aged↗

PubMed1991

Simplifying environmental cues in a Morris-type water maze improves place learning in old NMRI mice.

Old virgin female NMRI mice aged 17 months were compared with mice aged 3 months for their spatial learning abilities in two versions of the Morris water maze. The first one was a simplified version with a salient configuration of cues comparable to a black/white discrimination and the second one was the classical version of the Morris test with many distal cues surrounding the maze. In the simplified version, old mice presented a slower rate of acquisition and a transient poorer retention compared to young mice. However, old mice achieved a final level of performance statistically comparable to their young counterparts as assessed by latencies to escape onto the concealed platform and by the spatial bias measured in probe trials at intervals during testing. When subsequently subjected to classical Morris maze learning, the same old animals showed marked learning deficits and were persistently impaired in their latencies to escape onto the platform. They presented no spatial bias for the location of the platform in the different probe trials. When the goal was cued at the end of the experiment, the performances of old mice rapidly improved, showing that motivation, motor disabilities, or fatigue and ability to use proximal cues cannot explain the place learning deficit. Our results were discussed in terms of cognitive versus sensory/perceptual disabilities in aged rats and mice.

Aging↗

PubMed2004

A novel version of the 8-arm radial maze: effects of cerebral ischemia on learning and memory.

A novel version of the 8-arm radial maze task was developed to quantify spatial learning and memory in rats subjected to transient cerebral ischemia (TCI) using the 4-VO model. This maze uses the rat's natural behavior of avoiding open, illuminated areas, and preference for a darkened, enclosed shelter. Ischemic rats were required to escape from the central area into the darkened goal box. Ischemia was induced before or after training to examine its influence on acquisition and retention of cognition, respectively. During the acquisition test, latency of ischemic rats to find the goal box, and working memory performance were significantly impaired (P < 0.005-0.001). The performance for retention of cognition was also disrupted by ischemia (P < 0.05-0.01). There was no correlation between the degree of CA1 pyramidal cell loss and behavioral deficits. The present data reveal that the aversive version of the 8-arm radial maze is sensitive to the cognitive effects of ischemia. Since it excludes the need for food deprivation or immersion of the animal in water, the method should provide a sensitive and more practical behavioral test with which to evaluate the effects of ischemic brain damage on cognition.

Animals↗

PubMed2004

Impact of enriched-environment housing on brain-derived neurotrophic factor and on cognitive performance after a transient global ischemia.

Environmental enrichment promotes structural and functional changes in the brain, including enhanced learning and memory performance in rodents. Transient global cerebral ischemia (15 min) causes specific damage to dorsal hippocampal area CA1 pyramidal cells of the rat concomitantly with cognitive deficits. Thus, we investigated if environmental enrichment can protect rats against the cognitive and neurological consequences of transient ischemia. We evaluated the impairment of learning and memory with three tasks: odour discrimination, object exploration and spatial learning. Contrary to expectation, we found that the enriched environment improved performances for both ischemic and sham rats in odour discrimination and object exploration tasks compared with standard condition housed rats. After exposure to an enriched environment, ischemic rats performed better in the water maze than those in the standard housing conditions. However, exposure to an enriched environment does not protect against actual loss of CA1 pyramidal cells. Brain-derived neurotrophic factor (BDNF) levels were increased in environmental enrichment animals compared to those housed in standard conditions. We conclude that environmental enrichment has positive effects that are independent of the effects of ischemic brain lesions.

Analysis of Variance↗

PubMed2006

A long-term video-EEG and behavioral follow-up after endothelin-1 induced middle cerebral artery occlusion in rats.

The aim was to test the hypothesis that occlusion of the middle cerebral artery (MCA) results in the development of epilepsy in rats. Further, we investigated whether lesion volume, hippocampal pathology, early seizures, or severity of behavioral impairment is associated with the development and severity of epilepsy or interictal spiking. MCA occlusion was induced by intracerebral injection of endothelin-1 (ET; 120 pmol). One group of ET-injected rats were followed-up for 6 months (n = 15) and another for 12 months (n = 20). Sham-operated animals were injected with saline (n = 12). Occurrence of early and late seizures was monitored by intermittent video-electroencephalography. Sensorimotor function was tested with the running wheel and tapered beam-walking tests. Emotional learning and memory were assessed with the fear conditioning test and spatial learning and memory with the Morris water maze. Finally, brains were processed for histology. Only one rat developed late spontaneous seizures (i.e., epilepsy). Epileptiform interictal spiking was detected in 9 of 26 animals. Early seizures did not predict the development of epilepsy, spiking activity, or severity of behavioral impairment. Production of MCA stroke by intracerebral injection of ET was not a strong trigger of epileptogenesis in adult rats. Further studies are needed to investigate the effect of age, genetic background, and location of ET-injection on the development of hyperexcitability and the risk of post-stroke epileptogenesis.

Animals↗

PubMed2001

Visual discrimination learning impairments produced by combined transections of the anterior temporal stem, amygdala and fornix in marmoset monkeys.

Marmoset monkeys (Callithrix jacchus) with bilateral transections of the anterior temporal stem, amygdala and fornix were unable to relearn a 2-choice object discrimination first learnt prior to surgery, and were very severely impaired at relearning a concurrent object discrimination task which they had learnt and relearnt prior to surgery, indicating that they had a dense retrograde amnesia. They also had difficulty learning new visual object discriminations but were only mildly impaired on spatial learning. When tested on new learning of concurrent discriminations 8 to 10 weeks after surgery, three operated monkeys were unable to reach criterion in 400 trials while the remaining two operated monkeys performed within the normal range. The operated monkeys were subsequently shown to be impaired on acquisition of shape discriminations using black objects. These anterograde effects suggest that the impairment runs mainly in the domain of visual analysis. The monkeys also exhibited many of the features of the Klüver-Bucy syndrome. Histological analysis indicated that in addition to cutting some of the subcortical temporal lobe efferent pathways, the surgical procedures had cut the cholinergic afferents to the temporal neocortex, entorhinal cortex, and hippocampus. In a second experiment we found that treatment with the cholinergic agonist pilocarpine, which is effective in monkeys with specific cholinergic lesions, was unable to remediate the lesion-induced impairments. This suggests that transection of the non-cholinergic afferents, or the temporal lobe subcortical efferents, contributed to the behavioural syndrome and the learning and retention deficits seen in these monkeys.

Acetylcholinesterase↗

PubMed2007

Developmental exposure to methylmercury alters learning and induces depression-like behavior in male mice.

To investigate the long-term effects of developmental exposure to methylmercury (MeHg), pregnant mice were exposed to at 0.5 mg MeHg/kg/day via drinking water from gestational day 7 until day 7 after delivery. The behavior of offspring was monitored at 5-15 and 26-36 weeks of age using an automated system (IntelliCage) designed for continuous long-term recording of the home cage behavior in social groups and complex analysis of basic activities and learning. In addition, spontaneous locomotion, motor coordination on the accelerating rotarod, spatial learning in Morris water maze, and depression-like behavior in forced swimming test were also studied. The analysis of behavior performed in the IntelliCage without social deprivation occurred to be more sensitive in detecting alterations in activity and learning paradigms. We found normal motor function but decreased exploratory activity in MeHg-exposed male mice, especially at young age. Learning disturbances observed in MeHg-exposed male animals suggest reference memory impairment. Interestingly, the forced swimming test revealed a predisposition to depressive-like behavior in the MeHg-exposed male offspring. This study provides novel evidence that the developmental exposure to MeHg can affect not only cognitive functions but also motivation-driven behaviors.

Alkaline Phosphatase↗

PubMed1994

Brain lesions and water-maze learning deficits after systemic administration of kainic acid to adult rats.

The relationship between hippocampal damage and spatial learning deficiencies was studied in rats injected with kainic acid (10 mg/kg i.p.). A single injection was given either before or after the acquisition phase of the Morris water-maze task. In this acquisition phase, the animals were required to find a hidden underwater platform starting from four different points. The task was repeated twice a day for 10 days. In the retention phase after 10 days rest, the rats repeated the same task. The damage caused by the treatment occurred in several prosencephalic areas, including the piriform and enthorhinal cortices, the thalamus and the hippocampus. In the latter, greatest damage was seen in CA1 followed by CA3 while CA2 and the gyrus dentatus appeared almost unaffected. The behavioural results indicated that kainic acid impaired but did not preclude the acquisition of the water-maze task. During the retention phase, no significant differences in latencies were found between animals that were treated before and after acquisition, thus, indicating that pretraining does not play an important role in the recovery of these spatial abilities following hippocampal lesions.

Animals↗

PubMed2000

Reduced visual acuity impairs place but not cued learning in the Morris water task.

The Morris water task is a standard method for testing spatial learning in rodents. In a place version of the task, animals utilize multiple visual cues to learn the location of a hidden platform. The ability of animals to locate a cued platform is often used to qualitatively test for possible non-cognitive contributions to deficient place learning, including reduced visual function. We investigated the role of visual acuity in water maze performance quantitatively by depriving rats of pattern vision during a critical period for visual plasticity, which reduced their acuity by approximately 27% and then tested them in typical place and cued platform configurations of the Morris water task. Animals with reduced visual acuity had a significant deficit in place learning, but eventually reached the same escape latency as non-deprived animals. Deprived and non-deprived animals, however, did not differ in their ability to locate a cued platform following place learning. These data indicate that reduced visual acuity in rats can influence measurement of their place learning and that a typical cued platform version of the task cannot detect a modest, but significant, visual deficit.

Animals↗

PubMed2006

Place learning strategy of substantia nigra pars compacta-lesioned rats.

The substantia nigra pars compacta (SNc) and the dorsal striatum are often considered to be necessary for stimulus-response (S-R) habit learning, whereas the dorsal hippocampus is considered to be necessary for relational (declarative) memory. Spatial learning is a kind of relational learning that occurs when a rat is released from different locations (variable start) in a water maze to find a submerged platform that is kept in a constant location. However, when the rat is always released from the same starting position (constant start), it can learn to find the platform oriented by a fixed configuration of cues, that is, by S-R learning. To test the critical role of the SNc in S-R and relational learning, the authors tested adult male Wistar rats, sham-operated or with a lesion in the SNc, in these 2 versions of the water maze task. The SNc lesion was induced by bilateral intranigral infusion of 0.5 micromol 1-methyl-4-phenyl- 1,2,3,6-tetrahydropyridine. Although the SNc-lesioned rats learned the variable-start version as effectively as sham rats did, they were significantly impaired in learning the constant-start version of the task.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗

PubMed1995

The effect of dizocilpine (MK-801) on spatial and visual discrimination tasks in the rat.

The present experiments investigated the effect of the non-competitive N-methyl-d-aspartate (NMDA)-receptor antagonist, dizocilpine (MK-801) (0.075mg/kg) on acquisition and reversal of either a spatial or a visual, appetitively rewarded, simultaneous discrimination task in a Y-maze. The experimental design for the spatial and the visual discriminations was identical, the only difference between the tasks being the nature of the stimulus. Dizocilpine had not effect on acquisition of the spatial task although, when this task was reversed, dizocilpine-treated rats took significantly more trials to reach criterion. On the visual task, dizocilpine impaired both acquisition and reversal. Thus, systemic administration of dizocilpine did not produce a specific spatial learning impairment. The fact that dizocilpine impaired reversal but not acquisition in the spatial task argues against a global performance deficit. Although both the acquisition and reversal phases of the experiment make equal sensory and motor demands on the animal, reversal involves specific learning processes that may be disrupted by dizocilpine.

Journal Article↗

PubMed1985

Learning and memory deficits after lesions of the nucleus basalis magnocellularis: reversal by physostigmine.

The role of the cholinergic nucleus basalis magnocellularis in spatial learning and memory was studied in the rat. Animals received bilateral injections of ibotenic acid (5 micrograms/microliters) into the region of the nucleus basalis magnocellularis. Six weeks postoperatively they were deprived of food and trained for 5 weeks in a 16-arm radial maze in which 9 of the arms were baited with food. The nucleus basalis magnocellularis-lesioned animals showed significant deficits in the acquisition of the task. Further analysis of the data indicated that this was due primarily to a deficit in reference (long-term) as opposed to working (short-term) memory. After the 5-week training period the nucleus basalis magnocellularis-lesioned animals received intraperitoneal injections of physostigmine sulphate (0.5 mg/kg) 30 min before each daily trial for 1 week. This treatment resulted in a significant improvement in the performance of the spatial memory task on all three measures. The ibotenate lesions reduced the activity of choline acetyltransferase by about 40% in the anterior cortex and by 15% in the posterior cortex. Hippocampal choline acetyltransferase activity was not affected, indicating that the septohippocampal cholinergic projection was spared by the lesions. The activity of glutamate decarboxylase was not affected in any of these regions. These results suggest that the cholinergic projections of the nucleus basalis magnocellularis play an important role in the acquisition of a spatial memory task.

Animals↗

PubMed2004

Sleep deprivation impairs hippocampus-mediated contextual learning but not amygdala-mediated cued learning in rats.

Prolonged sleep deprivation results in cognitive deficits. In rats, for example, sleep deprivation impairs spatial learning and hippocampal long-term potentiation. We tested the effects of sleep deprivation on learning in a Pavlovian fear conditioning paradigm, choosing a sleep deprivation paradigm in which REM sleep was completely prevented and non-REM sleep was strongly decreased. During conditioning, rats were given footshocks, either alone or paired with a tone, and tested 24 h later for freezing responses to the conditioning context, and to the tone in a novel environment. Whereas control animals had robust contextual learning in both background and foreground contextual conditioning paradigms, 72 h of sleep deprivation before conditioning dramatically impaired both types of contextual learning (by more than 50%) without affecting cued learning. Increasing the number of footshocks did not overcome the sleep deprivation-induced deficit. The results provide behavioural evidence that REM/non-REM sleep deprivation has neuroanatomically selective actions, differentially interfering with the neural systems underlying contextual learning (i.e. the hippocampus) and cued learning (i.e. the amygdala), and support the involvement of the hippocampus in both foreground and background contextual conditioning.

Amygdala↗

PubMed2004

Cholecystokinin tetrapeptide improves water maze performance of neonatally 6-hydroxydopamine-lesioned young rats.

This study addressed the proposed memory-modulating effect of the cholecystokinin (CCK) 2 agonist Boc-CCK-4 in rats using a Morris water maze. In the brain, CCK is colocalized and interacts with dopamine, respectively. To impair dopaminergic neurotransmission, and consequently, dopamine-mediated learning and memory, rat pups received the neurotoxin 6-hydroxydopamine (6-OHDA) into the left [Day 5 postnatal (p.n.)] and right (Day 8 p.n.) ventricles (50 microg/5 microl each). After 6-OHDA treatment, dopamine brain levels were reduced by 60% on Day 50 p.n. Lesioned rats had a lower body weight but normal swimming abilities. In the acquisition phase of the water maze (Day 50 p.n.), sham-lesioned rats learned quickly, compared to lesioned rats. Treatment with Boc-CCK-4 (40 microg/kg ip) did not affect performance in sham-lesioned rats but restored the learning curve in lesioned rats without increasing swimming speed indicating a better spatial learning in the dopamine-depleted rats. In summary, these findings demonstrate that stimulation of CCK2 receptors may counteract cognitive deficits of dopamine-depleted rats.

Animals↗

PubMed2002

Morphine conditioned reward is inhibited by MPEP, the mGluR5 antagonist.

In the present study we examined the effect of MPEP [2-methyl-6-(phenylethynyl)-pyridine] a potent, selective and systemically active metabotropic glutamate receptor (mGluR) type I (subtype mGluR5) antagonist on conditioned morphine reward in mice. In an unbiased version of conditioned place preference (CPP) paradigm, single conditioning with 10 mg/kg of morphine produced reliable place preference. MPEP at 30, but not 10 mg/kg significantly inhibited the acquisition as well as expression of morphine-induced CPP, but it neither produced place preference or aversion, nor affected locomotor activity of mice. Effects of MPEP on learning and memory were studied in the elevated plus maze model of spatial learning. In contrast to 0.1 mg/kg of MK-801, which inhibited the acquisition of this task, 30 mg/kg of MPEP affected neither learning nor memory retrieval. These data suggest that mGluR5 may be involved in conditioned morphine reward.

Animals↗