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Spatial memory and N-methyl-D-aspartate receptor antagonists APV and MK-801: memory impairments depend on familiarity with the environment, drug dose, and training duration.

Rats given N-methyl-D-aspartate (NMDA) antagonists were tested in the radial maze in spatial working memory (WM) and reference memory (RM) tasks. Female rats given (+)-10,11-dihydro-5-methyl-5H-dibenzo [a,d] cycloheptene-5,10 imine (MK-801; 0.0625 mg/kg ip) before daily testing in an 8-arm WM task were impaired even after 70 days. Control rats learned quickly, were assigned to a group given MK-801 or saline, and were trained to avoid 4 of the 8 arms. MK-801 impaired this reversal learning but did not affect WM performance. Male rats were trained on an 8-arm WM task for 19 days and then given intracranial aminophosphonovaleric acid (APV; 33 mM), which impaired both WM and motor behavior. Male rats were trained for 65 days to enter 4 of 8 arms and then given intracranial APV (20 or 30 mM). WM and RM were normal in the familiar environment but were both impaired in an unfamiliar environment. Results suggest that the mnemonic effects of NMDA antagonists depend on environmental familiarity, dose, and training duration.

2-Amino-5-phosphonovalerate

Behavioral parameters of the spatial memory correlate with the potentiation of the population spike, but not with the population excitatory postsynaptic potential, of the CA1 region in rat hippocampal slices.

Rats were tested for spatial performance in a water maze with further in vitro investigation of short-term and long-term potentiation (STP and LTP) in the CA1 region of the hippocampus. Recordings of the population spike in stratum pyramidale and population excitatory postsynaptic potential (EPSP) in stratum radiatum were made with extracellular electrodes after stimulation of the radiatum and oriens inputs in the region. It was found that for both inputs, STP and LTP of the population spike amplitude correlated with behavioral parameters of memory: latency of reaching the hidden platform (escape latency) and percent of time which the animal spent inside the quadrant with the platform. Potentiation of the initial slope of EPSP, in contrast, did not correlate with these parameters. These data support the hypothesis that hippocampal LTP may underlie spatial performance and show that potentiation of the output characteristic of the hippocampus (population spike), but not of the EPSP, is a physiological correlate for spatial memory.

Action Potentials

The retrieval of visuo-spatial memories by honeybees.

In order to explore how honeybees manage to retrieve the right landmark-memory in the right place, we trained bees along a short foraging route which consisted of two identical huts 33 m apart. Bees entered each hut to collect a drop of sucrose on the floor. The location of the drop was defined by the same arrangement of four blue and yellow cylindrical landmarks. However, in one hut the drop was between two yellow cylinders and in two other it was to the east of the blue cylinders. On tests with the sucrose missing, bees tended to search in the appropriate area in each hut (Fig. 1), thus showing that they used cues other than the sight of the local landmarks to select the appropriate memory. In a second experiment, the position of the sucrose was specified by yellow cylinders in one hut and by blue triangles in the other. When the arrays were swapped between huts, bees searched in the position specified by the array they encountered (Fig. 2). Thus, memories can be triggered by visual features of local landmarks. Bees were also trained outside to collect food from two platforms 40 m apart. The location of sucrose on one platform was defined by yellow cylinders, and on the other it was defined by blue triangles. When these arrays were exchanged between platforms, bees searched on each platform as though the landmarks had not been swapped. It seems that the more distant surroundings, which fill most of the visual field, may be more potent than the local landmarks in deciding which memory should be retrieved.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Previous experience facilitates preservation of spatial memory in the senescent rat.

In an attempt to evaluate whether previous training antagonizes age-related memory deficits, aged rats with previous training experience were compared with aged and young naive rats in the Morris water maze test. The findings of our study indicate that experience seems to facilitate the preservation of the spatial reference memory for 12 months in the aged rat, whereas senescent naive animals showed the usual age-related memory deficits. However, experience seems task-specific since the same aged rats fail to acquire a new different task.

Aging

In situ binding of bouton zinc reversibly disrupts performance on a spatial memory task.

Neurons with zinc in the presynaptic vesicles innervate much of the telencephalon, but the functional significance of the vesicular zinc has never been established. The present work shows that reversible binding of zinc by drug infusion into the hippocampus produces a time-locked and selective disruption of hippocampal-dependent spatial-working memory. A role for vesicular zinc in neurotransmission or neuromodulation is implied.

Animals

[A test for the evaluation of visuo-spatial memory].

Review of available literature reveals the lack of reports on memory impairment in relation to visuo-spatial and tridimensional dominance. Considering the absence of specific methods for assaying evaluations, the intention of our study was to devise a systematic testing procedure in order to explore the patterns referrable to this aspect.

Adolescent

Amelioration of spatial memory impairment by intrahippocampal grafts of mixed septal and raphe tissue in rats with combined cholinergic and serotonergic denervation of the forebrain.

Previous studies in the rat have shown that a serotonergic depletion greatly potentiates the learning and memory impairments produced by pharmacological or lesion-induced cholinergic blockade in the forebrain. The impairment produced by combined serotonergic-cholinergic lesions is reminiscent of that seen in memory-impaired aged rats. In the present experiment, we investigated whether grafts of cholinergic septal tissue and serotonergic mesencephalic raphe tissue, placed in the hippocampus, could reverse the severe memory impairment produced by combined cholinergic-serotonergic lesions. Adult rats were given an intraventricular injection of 5,7-dihydroxytryptamine followed by a radiofrequency lesion of the septum 1-2 weeks later. Three weeks after lesion surgery, the rats were given bilateral intrahippocampal cell suspension grafts of either fetal septal or mesencephalic raphe tissue, or both. The rats were tested for spatial learning and memory in the Morris water maze task at 4 and 10 months after grafting. At 4 months, lesioned and grafted groups were all impaired compared to the normal controls in their swim time and distance swum to find the platform, and they did not show any spatially focussed search strategy in the spatial probe trial when the platform was removed from the tank. At 10 months, the rats with mixed cholinergic and serotonergic grafts were no longer impaired compared to normals in their swim time and distance to find the platform, and they were significantly improved compared to the other grafted groups. Moreover, in the spatial probe trial, the rats with mixed cholinergic and serotonergic grafts displayed a spatially focussed search behaviour over the previous platform site, which was not seen in the lesioned control rats or in the other graft groups. Morphological analysis of the hippocampus revealed that the septal grafts produced an acetylcholinesterase-positive innervation but were totally devoid of serotonin innervation. The raphe grafts produced mainly a serotonin innervation, of both acetylcholinesterase- and serotonin-positive fibres. The results suggest that a mixture of septal and raphe tissue is required when grafted to the hippocampal formation in order to ameliorate the severe spatial learning and memory impairments produced by a combined cholinergic and serotonergic denervation, and that each of these graft types separately are not sufficient to ameliorate such deficits.

Animals

A homing procedure for studying spatial memory in immature and adult rodents.

In this procedure, subjects learn the spatial position of one hole out of many, that allows them to escape from a large open-field into their home cage. The arena is circular and can be rotated between trials so that no proximal landmark is permanently associated with the target hole. This task is thus similar to the Morris water maze procedure, since subjects must remember the position of the escape hole relative to extra-arena cues only. In addition it allows studying the importance of olfactory cues such as scent marks in or around a hole. Since the motivation is to reach home and the motor requirement is low, this task provides a useful alternative to the Morris place navigation task for studying spatial orientation in weanling or senescent rats. Examples are given showing that various behavioural parameters provide a good estimation as how subjects learn this task.

Animals

GABAergic mediation of indirect transsynaptic control over basal and spatial memory testing-induced activation of septo-hippocampal cholinergic activity in mice.

A neurochemical study of the transsynaptic interactions established between septal GABAergic interneurones and cholinergic septo-hippocampal neurones was conducted using mice. The effects of acute in vivo injections of either muscimol (20-500 ng/0.2 microliter), bicuculline (100 ng-1 micrograms/0.2 microliter) or saline vehicle (0.2 microliter) into the medial septum on septo-hippocampal cholinergic activity were evaluated using measures of hippocampal high affinity choline uptake at 30 min post-injection in two main groups of mice. The first (quiet control) remained in their home cages during the post-injection period whereas the second (active) were submitted, 10 min following injection to a 20-min period of spatial working memory testing in an 8-arm radial maze. Intraseptal injections of either muscimol or bicuculline produced significant (25-50%) inhibition of hippocampal cholinergic activity in quiet conditions (basal) as compared to intact or saline-injected mice. In the active groups, whereas memory testing induced significant cholinergic activation (+15-20%) in intact and saline injected mice at 30 s post-test no significant memory testing-induced activation was observed in either muscimol or bicuculline-injected mice at any dose. The role of septal GABAergic interneurones in the indirect transsynaptic control over the basal and activated states of septo-hippocampal cholinergic activity is discussed with respect to the concept that these complex neuronal interactions contribute to the physiological mechanisms involved in the modulation of working memory performance.

Animals

The selective 5-HT3 receptor antagonist, WAY100289, enhances spatial memory in rats with ibotenate lesions of the forebrain cholinergic projection system.

The effects of three doses (0.003, 0.03 and 1.0 mg/kg sc) of the 5-HT3 receptor antagonist, WAY 100289, on spatial learning and memory in the water maze were examined in rats before and after ibotenate lesions to the nucleus basalis and medial septal brain regions at the source of cholinergic projections to cortex and hippocampus. The representative cholinergic nicotinic and muscarinic receptor agonists nicotine (0.1 mg/kg) and arecoline (1.0 mg/kg) were also tested for comparison. Both arecoline and nicotine improved initial acquisition in rats before lesioning, in terms of latency to find a hidden platform and accuracy of search strategy. WAY100289 did not affect the performance of normal rats significantly, apart from some non-significant trends towards improvement with the highest dose. However, in animals showing transient navigational deficits in retention and relearning after lesioning, WAY100289 improved performance at all three doses, though ameliorative effects of nicotine and arecoline were more marked also in lesioned rats. These results show that WAY100289 improved spatial learning in animals impaired after lesions to cholinergic projection nuclei, which may reflect an interaction with cholinergic transmission to enhance cognitive function. However, in the present study, WAY100289 appeared to be less effective than direct cholinergic agonists.

Animals

The effects of reversible inactivations of the hippocampus on exploratory activity and spatial memory.

This study was aimed at testing the effects of a reversible inactivation of the ventral hippocampus on behavior in response to a change, following a period of habituation with a hippocampus that functions normally. A new dishabituation paradigm was used, which allowed the testing of visuospatial memory. A salient stimulus was placed under the glass floor of the apparatus during initial exploration and was removed during the test session. The time spent above the zone where the stimulus was initially located indicated the rats' reaction to the change. Unlike the control rats who reacted to the removal of the salient stimulus by reexploring its previous location, lidocaine-injected subjects did not display any similar searching behavior. Experiment 2 examined the hypothesis that landmarks located under the floor could help hippocampus-inactivated animals to accurately react to the change. Two objects were located either close to the stimulus or some distance away from it. Even when the objects were closely associated to the stimulus, the same failure to react to the removal of the stimulus was found in lidocaine-injected rats. However, these animals displayed a higher activity level measured by the time spent on a "neutral" zone. This behavioral pattern suggests a specific localization deficit. The method of reversible inactivation appears to be a promising approach to the study of the time course of memory process with short-term experimental paradigms such as those used in the present study.

Animals

[Characteristics of the role of spatial memory in the choice reactions of white rats].

Behaviour of the rats, previously learnt to come back to one and the same place of reinforcement was studied in conditions of periodical changes of this place. It was found that after detection of the new place of reinforcement, the rats could optimize their behaviour according to disposition of this place. Optimization of behaviour consisted in shifts of running direction towards the new reinforcement place and (or) in selective displacements before blinds, according to the places of reinforcement in the experiment. It is suggested that an increase of the role of working memory and apparatus of probabilistic prognosis at choice lies in the basis of optimization.

Animals

Spatial memory by blind and sighted children.

Non-verbal recall of haptically presented spatial positions by three age groups of blind and sighted children was tested under conditions varying cueing, recall type and stimulus position in a within-subject design. Slighted status was not only significant, but interacted significantly with recall type, and further with stimulus position, consistent with sequential haptic by blind and quasi-simultaneous visual processing by sighted children. Age was significant, but its only significant interaction was a relatively small one with cueing conditions and stimulus position, suggesting that the oldest group, regardless of sightedness, used verbal strategies in pre-cued conditions. The findings support the hypothesis that visual and haptic modalities of representation have demonstrably different effects on processing and efficiency in spatial recall, but counterindicate the hypothesis that these relate differentially to age. Results also suggest that a combination of cue utilization and verbal strategies is a significant, but relatively minor, factor in improvements in spatial recall.

Age Factors