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Double dissociation of function within the hippocampus: spatial memory and hyponeophagia.

Complete and dorsal hippocampal lesions impaired spatial performance on 2 working memory tasks: rewarded alternation on the T maze and matching to position in the water maze. In contrast, ventral hippocampal lesions had no effect on these tasks, even when task difficulty was increased by the introduction of delays. Ventral lesions did resemble complete lesions in reducing anxiety in 3 commonly used tests of anxiety (social interaction, plus-maze, and hyponeophagia). Dorsal lesions also appeared to be anxiolytic in the social interaction and plus-maze tests, but they did not affect hyponeophagia. Complete- and dorsal-lesioned rats displayed hyperactivity, whereas ventral-lesioned rats did not. These results show a double dissociation between dorsal and ventral hippocampal lesions (hyponeophagia vs. spatial memory), suggesting differentiation of function along the septotemporal axis of this structure.

Amphetamine↗

Imposing structure on a Corsi-type task: evidence for hierarchical organisation based on spatial proximity in serial-spatial memory.

Structure was imposed on a tapping task by requiring participants to reproduce sequences of responses to icons organised in spatial clusters. A first experiment featured sequences either segregated or not segregated by clusters. Accuracy was higher for sequences segregated by clusters. Moreover, inter-response times were longer at cluster boundaries than within cluster boundaries. To rule out possible confounding effects of movement length, this temporal pattern was replicated in a second experiment requiring a single response indicating the next sequential step, following the presentation of a portion of a previously practised sequence. These results suggest that sequence reproduction can be sustained by a hierarchical representation based on spatial proximity and provide a first indication of the role of spatial structure in serial-spatial memory.

Adolescent↗

Enrichment enhances spatial memory and increases synaptophysin levels in aged female mice.

The present study tested whether environmental enrichment can reduce age-related spatial reference memory deficits and alter synaptic protein levels in aged female mice. Female C57BL/6 mice, (4 or 27-28 months), were tested in spatial and cued Morris water maze tasks. Prior to (14 days) and during testing, a subset of aged females was exposed to rodent toys and running wheels for 3h per day. The remaining aged females were group housed but were not exposed to enriching objects. At the conclusion of testing, levels of the presynaptic protein synaptophysin were measured in hippocampus and frontoparietal cortex. Enrichment improved spatial memory acquisition; relative to young controls, aged enriched females performed similarly, whereas aged control females were impaired. Enrichment also accelerated the development of a spatial bias in spatial probe trials. In contrast, the cued task was not significantly affected by enrichment. Hippocampal and cortical synaptophysin levels were increased in aged enriched females relative to young and aged controls. These data suggest that environmental enrichment can be a potent cognitive enhancer for aged females and suggests a potential neurobiological mechanism of this effect.

Aging↗

NGF improves spatial memory in aged rodents as a function of age.

Aged rats were tested for place navigation in a circular water maze for spatial memory ability at 18 and 30 months of age; 45% of the 18-month-old rats displayed impaired place navigation performance relative to young control rats, while essentially all of the 30-month-old rats were impaired. The aged impaired rats were retested twice during NGF or vehicle infusion in the right lateral ventricle. In the 18-month-old group, NGF-infused rats showed improved retention of previously acquired place navigation performance and improved spatial acuity over the former platform site when the invisible platform was removed. NGF infusion also had a significant effect in the much more severely impaired 30-month-old rats: while the vehicle-infused aged rats showed a progressive decline in the performance between the first and second test weeks, the performance of the NGF-infused rats remained stable throughout the infusion period. The interpretation of these effects in the oldest animals, however, was confounded by a progressive decline in swim speed seen in the vehicle-infused animals. The 30-month-old vehicle-infused control rats showed a significant cell loss and cell shrinkage relative to the young control rats in the septal/diagonal band area, the striatum, and the nucleus basalis as assessed by NGF-receptor (NGFr) and ChAT double-label immunocytochemistry. A significant increase in the size but not in the number of cells was observed on the side of the NGF infusion in the 30-month-old NGF-infused rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗

The modified Location Learning Test: norms for the assessment of spatial memory function in neuropsychological patients.

This study examines the applicability of the modified Location Learning Test (mLLT) as a test of spatial memory in neuropsychological patients. Three groups of participants were examined: stroke patients, patients with diabetes mellitus and healthy participants (N=411). Three error measures were computed, the Total Score (index of overall performance), the Learning Index (the learning curve over subsequent trials) and the Delayed Recall Score, measuring decay over time. The Learning Index was the most sensitive measure, showing differences between the three groups as well as lateralization effects within the stroke group. Also, the mLLT correlated significantly with the Rey Auditory Verbal Learning Test, as well as with age and education level. Regression-based normative data were computed based on the healthy participants. In all, the mLLT appears to be a sensitive and valid test for the detection of object-location memory impairments in clinical groups.

Adolescent↗

[Neural basis for spatial memory in animals: what do hippocampal neurons tell us?].

Recent studies relying on the recording of neuronal unit activity in freely moving rats show the existence of two populations of neurons signalling the animal's location or head direction: place cells found primarily in the hippocampus and head direction cells found in brain areas anatomically and functionally related to the hippocampus. The properties of these two neuronal populations suggest that their activity strongly depends upon information cues stemming from the spatial environment, and also suggest their involvement in spatial memory. Place cells and head direction cells would jointly participate in a neural network allowing the animal to orient in space and to store spatial locations in memory. This network would also be operating in humans, in particular for encoding specific events in episodic memory.

Animals↗

A study on the effect of lesions of area 7 of the parietal cortex on the short-term visual spatial memory of rhesus monkeys (Macaca mulatta).

This research is focused on the contribution of area 7 to the short-term visual spatial memory. Three rhesus monkeys (Macaca mulatta) were trained in the direct delayed response task in which 5 delay intervals were used in each session. When each monkey reached the criterion of 90% correct responses in 5 successive sessions, two monkeys underwent a surgery while the other one received a sham operation as a control. In the first stage of the surgery, bilateral areas 7a, 7b and 7ip of the parietal cortex of two monkeys were precisely lesioned. After 7 days of recuperation, the monkeys were required to do the same task. The average percentage of correct responses in the lesioned animals decreased from 94.7% to 89.3% and 93.3% to 82.0% respectively (no significance, P > 0.05, n = 2). In addition, the monkeys' complex movements were mildly impaired. The lesioned monkeys were found to have difficulty picking up food from the wells. In the second stage, bilateral area 7m was lesioned. In the 5 postoperative sessions, the average percentage of correct responses in one monkey, with a relatively precise 7m lesion, decreased from 94.7% to 92.2% (no significance, P > 0.05), while the other monkey, with widely spread necrosis of lateral parietal cortex, showed an obvious decline in performance, but still over the chance level. After 240 trials this monkey reattained the normal criterion.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Involvement of brain-derived neurotrophic factor in spatial memory formation and maintenance in a radial arm maze test in rats.

Brain-derived neurotrophic factor (BDNF) regulates both short-term synaptic functions and activity-dependent synaptic plasticity such as long-term potentiation. In the present study, we investigated the role of BDNF in the spatial reference and working memory in a radial arm maze test. The radial arm maze training resulted in a significant increase in the BDNF mRNA expression in the hippocampus, although the expression in the frontal cortex did not change. When spatial learning was inhibited by treatment with 7-nitroindazole, an inhibitor of brain nitric oxide synthase, the increase in the hippocampal BDNF mRNA did not occur. To clarify the causal relation between BDNF mRNA expression and spatial memory formation, we examined the effects of antisense BDNF treatment on spatial learning and memory. A continuous intracerebroventricular infusion of antisense BDNF oligonucleotide resulted in an impairment of spatial learning, although the sense oligonucleotide had no effect. Treatment with antisense, but not sense, BDNF oligonucleotide was associated with a significant reduction of BDNF mRNA and protein levels in the hippocampus. Furthermore, treatment with antisense BDNF oligonucleotide in rats, which had previously acquired spatial memory by an extensive training, impaired both reference and working memory. There were no differences in locomotor activity, food consumption, and body weight between the antisense and sense oligonucleotide-treated rats. These results suggest that BDNF plays an important role not only in the formation, but also in the retention and/or recall, of spatial memory.

Analysis of Variance↗

Re-evaluation of the spatial memory deficits induced by hippocampal short lasting inactivation reveals the need for cortical co-operation.

Evidence has accumulated that the rat hippocampus plays a central role in spatial memory. In complement to lesion studies, reversible lidocaïne-induced inactivations have been used to investigate the time-course of the memory processes mediated by the hippocampus. A number of studies suggest that, in some conditions, the hippocampus is not necessary for online acquisition of spatial information. To test this hypothesis, we examined the effects of bilateral lidocaïne-induced inactivations of the dorsal hippocampus in the acquisition of new spatial information. After initial learning of a place navigation task in the water maze, rats were tested for acquisition of a new platform location and received injections of lidocaïne in the hippocampus prior to each daily four-trial block. The training blocks were separated by a 24-h period allowing the hippocampus to recover from inactivation. The results show that lidocaïne-injected rats were able to learn the new platform location like controls. Inactivations, however, was found to induce a within-block learning impairment. This suggests that the hippocampus can perform off-line processing and that another structure is able to handle spatial information during hippocampal inactivations. Parietal-lesioned rats that received an injection of lidocaïne were still able to learn the new platform location suggesting that the parietal cortex does not sustain this role. Overall, our results suggest that the hippocampus is not necessary for all stages of memory formation and co-operates with other brain, possibly cortical, structures which remain to be determined.

Anesthetics, Local↗

Spatial memory deficits following stimulation of hippocampal 5-HT1B receptors in the rat.

In this study we examined a possible contribution of serotonin (5-hydroxytryptamine, 5-HT) to spatial memory performance in the rat. Rats were trained to run in a radial maze in a manner that involved two kinds of memory function, i.e. working memory and reference memory. They received intrahippocampal microinjections of a 5-HT1A [8-hydroxy-2-(di-n-propylamino)tetralin or 8-OH-DPAT], or a 5-HT1B [3-(1,2,5,6-tetrahydropyrid-4-yl)pyrrolo[3,2-b]pyrid-5-one or CP-93,129] receptor agonist, and a muscarinic receptor antagonist (scopolamine). 8-OH-DPAT (5 micrograms/microliters), like injections of saline, induced no change in performance levels. In contrast, rats suffered an impairment in both reference and working memory following injection of scopolamine (10 micrograms/microliters). CP-93,129 induced a higher frequency of reference memory errors than of working memory errors at the intermediate (10 micrograms/microliters) and higher doses (16 micrograms/microliters). Thus, the stimulation of 5-HT1B receptors in the CA1 field of the dorsal hippocampus impairs the performance of rats in a spatial learning task.

8-Hydroxy-2-(di-n-propylamino)tetralin↗

Spatial memory deficits in aged rats: contributions of monoaminergic systems.

Age-dependent changes in monoaminergic systems and their relationship to senescent memory decline were investigated in 4- and 25-26-month-old, female, Fischer 344 rats. Spatial memory performance was tested on an 8-arm radial maze, and levels of norepinephrine (NE), dopamine (DA) and metabolites 3,4-dihydroxyphenylacetic acid and homovanillic acid, serotonin (5-HT) and metabolite 5-hydroxyindoleacetic acid were measured in brain areas which contribute to memory function--basal forebrain cholinergic nuclei, subfields of the hippocampus, frontal and entorhinal cortex--and in monoaminergic cell body areas. The performance of aged subjects was significantly impaired as compared to young subjects, and alterations of 20-60% in monoamine and metabolite levels were measured in specific brain areas of aged rats. Decreased NE levels were found in basal forebrain nuclei and cortical areas but not in hippocampal subfields of aged rats. Changes in the 5-HT system were present in hippocampal, cortical and basal forebrain sites. Changes in the DA system were the most pervasive with aged rats showing decreased DA and/or metabolites in several basal forebrain nuclei, cortical areas, and the hippocampus. Aged rats showed 50% decreases of monoamines in locus coeruleus and substantia nigra and 30% decreases in the dorsal raphe nucleus. Some but not all of the changes correlated with memory performance. The present results in rats support evidence that age-dependent changes in monoaminergic function in discrete brain sites contribute to senescent memory decline and suggest that monoaminergic-cholinergic interactions within basal forebrain nuclei may be important in this decline.

Aging↗

Activation of CB1 cannabinoid receptors in rat hippocampal slices inhibits potassium-evoked cholecystokinin release, a possible mechanism contributing to the spatial memory defects produced by cannabinoids.

Cannabinoid use is known to disrupt learning and memory in a number of species. cholecystokinin (CCK) release and CCK receptors have been implicated in spatial memory processes in rodents. Rat hippocampal CCK interneurons express cannabinoid 1 receptors (CB1). The CB1 agonist R(+)WIN 55,212-2 (WIN+), at 1 and 10 micromol, strongly inhibited potassium-evoked CCK release from rat hippocampal slices, while the inactive isomer S(-)WIN,55,212-3 (WIN-) had no effect. CCK release from cerebral cortical slices was not altered by WIN+.

Animals↗

[The Location Learning Test as a measure of spatial memory: applicability of a modified administration procedure and normative data].

The Location Learning Test is a neuropsychological test that can be used to assess memory for object locations. The test has originally been developed for the assessment of visuo-spatial memory impairment in patients with dementia. However, ceiling effects may be present in other patient groups. This study has examined the applicability of a modified administration procedure with a shorter presentation duration and longer delay. The test was administered in a group of stroke patients (n = 105), a group of patients with diabetes (n = 93), as well as a group of healthy volunteers (n = 97). The results indicate that the Location Learning Test can be used to discriminate the diabetes and stroke patients from the control group. Furthermore, differences between patients with a left and a right-hemisphere stroke were found. The test has a high correlation with another memory test. The performance of the group healthy volunteers was used to calculate normative data for use in clinical practice.

Adolescent↗

Ginkgo biloba promotes short-term retention of spatial memory in rats.

This study examines possible interactions between exposure to Ginkgo biloba extract and enriched environments on the acquisition and retention of spatial learning following massed and spaced trials. After 4 weeks of exposure to either ginkgo or vehicle, 8-week-old rats were tested using a Morris Water Maze in either massed or spaced trials. While ginkgo did not have an effect on maze acquisition or long-term retention, it did promote short-term retention of spatial memory. Following reversal training, ginkgo promoted short-term retention for two groups but impaired retention for a third. These results suggest that ginkgo has powerful effects on short-term retention that vary with training conditions.

Animals↗

How marsh tits find their hoards: the roles of site preference and spatial memory.

Marsh tits (Parus palustris) store single food items in scattered locations and recover them hours or days later. Some properties of the spatial memory involved were analyzed in two laboratory experiments. In the first, marsh tits were offered 97 sites for storing 12 seeds. They recovered a median of 65% of them 2-3 hr later, making only two errors per seed while doing so. Over trials, they used some sites more often than others, but during recovery they were more likely to visit a site of any preference value if they had stored a seed there that day than if they had not. Recovery performance was much worse if the experimenters moved the seeds between storage and recovery. A fixed search strategy that had some of the same average properties as the tits' search behavior also did worse than the real birds. In Experiment 2, any tendency to visit the same sites on successive daily tests in the aviary was placed in opposition to memory for storage sites by allowing the tits to store more seeds 2 hr after storing a first batch. They tended to avoid individual storage sites holding seeds from the first batch. When the tits searched for all the seeds 2 hr later, they tended to recover more seeds from the second batch than from the first, i.e., there was a recency effect.

Animals↗

The effects of NMDA lesions centered on the postrhinal cortex on spatial memory tasks in the rat.

Rats with bilateral N-methyl-D-aspartate lesions centered on the postrhinal cortex (POR) and sham lesions were tested in a series of spatial memory tasks. The POR-lesioned rats were significantly impaired compared with sham rats in the reference memory version of both the water maze and radial arm maze tasks and in the standard radial arm maze working memory task. The POR-lesioned rats displayed a delay-independent impairment in the working memory versions of the water maze and in a delayed nonmatching-to-place (DNMP) version of the radial arm maze task. The POR-lesioned rats were also impaired in a DNMP procedure conducted in the T-maze. These findings indicate that the POR has a delay-independent role in the processing of spatial information.

Analysis of Variance↗

Obstructive jaundice in rats: cause of spatial memory deficits with recovery after biliary decompression.

Children with end-stage liver disease have been found to have cognitive deficits. The aim of this study was to examine whether cholestatic jaundice causes spatial deficits in rats and if these cognitive deficits are reversed by biliary drainage. Rats were randomly divided into three groups. In the first group, the bile duct was ligated for 3 weeks (BDL group); in the second group, the proximal bile duct was ligated with a Broviac CV catheter for 2 weeks followed by a tube bilioduodenostomy (TBD group); in the third group, a sham operation was performed (SHAM group). All the surviving rats were assessed for spatial learning and memory (a major cognitive function in rats) by the Morris water maze task about 3 weeks after the first operation. Blood was aspirated by cardiocentesis and assayed for total bilirubin, albumin, ammonia, and hemoglobin levels on the day following the water maze task. During the four consecutive acquisition trial days of the Morris water maze, jaundiced rats (BDL group) had a significant longer latency to escape than the SHAM group ( p < 0.05). Rats that underwent biliary decompression for 1 week (TBD group) showed improved status of the spatial deficit, as they required less time to reach the escape platform, approaching the performance of the SHAM group. The BDL group had a significantly higher serum ammonia level, higher bilirubin level, and lower hemoglobin level than the other two groups. After biliary decompression for 1 week, the serum albumin concentration in the TBD group still did not return to the level of the SHAM group. The results of this study suggest that long-term cholestasis results in spatial memory deficits in rats that correlate with anemia and hyperbilirubinemia encephalopathy. Early biliary decompression of obstructive jaundice improves spatial memory deficits, possibly related to the recovery of the serum ammonia and hemoglobin levels.

Analysis of Variance↗

Pigs shift too: foraging strategies and spatial memory in the domestic pig.

In a previous experiment, we showed that domestic pigs, Sus scrofa, unlike many other species, performed accurately in a spatial memory task, where visits to a previously baited food trough were rewarded (win-stay). We investigated whether pigs have a predisposition for this strategy, by comparing their performance in a radial arm maze under either win-stay (N=10) or win-shift (N=10) reward contingencies. Contrary to our earlier results, only one of the animals in the win-stay condition was able to reach the imposed criterion level of accuracy. The performances of the other win-stay pigs did not deviate from random. All pigs in the win-shift condition reached criterion by day 25 of the experiment, and performed better than expected by chance. Analysis of the types of errors made matched our a priori predictions that shift movements would occur more frequently, especially within visits to the maze. We suggest that the difference in learning rates may reflect the fact that win-stay pigs needed to use two different rules, stay between trials and shift within trials, while win-shift pigs only needed to use the shift rule. In our previous study, win-stay pigs did not experience a conflict of rules and this may have facilitated stay learning. We found evidence of a recency effect in win-shift animals and a primacy effect in the win-stay group. However, we discuss the unsuitability of these specific terms in this type of experiment, and propose an alternative interpretation of the results. Copyright 2000 The Association for the Study of Animal Behaviour.

Journal Article↗