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Can age-related deficits in spatial memory be attenuated through the use of verbal coding?

In a sequential mental rotation task, women of three age groups (18-28, 50-60, and 70-80) viewed semi-abstract figures which were rotated in the picture plane. To investigate the effects of verbal mediation, each figure was presented under one of four labeling conditions. Errors increased as a function of age. Meaningful labels were beneficial in decreasing errors for the older subjects. Reaction time results generally replicated earlier studies, but there were indications that some women in the oldest group might have used strategies other than mental rotation. Results suggest that possible age related deficiencies in spatial abilities may be compensated for by greater use of verbal mediation.

Adolescent↗

Locomotion, active choice, and spatial memory in children.

In two studies, children between 4 and 6 years old were tested on a radial search task requiring nonredundant sampling of eight identically labeled positions in a room. In the training phase (5 days), children made free choices by walking between positions, were passively transported in a pushchair, actively directed their own route from a pushchair, or were led on foot to positions selected by the experimenter. When tested (whether walking or directing while seated in a pushchair), children who had either walked independently or directed the experimenter while being pushed performed competently; those led on foot without spatial choice performed almost as well. Only the children who had neither independent locomotor experience nor autonomous choice performed very poorly. The results are related to neurobiological models of spatial cognition and may have implications for the transportation of children with mobility problems.

Child, Preschool↗

Behavioral manipulation of retrieval in a spatial memory task for Drosophila melanogaster.

A paradigm for operant conditioning of freely walking single Drosophila flies has been described previously. A fly can be conditioned to avoid one side of a small test chamber if the chamber is heated whenever the fly enters this side. In a subsequent memory test without heat the fly continues to avoid the previously heat-associated side. In this experimental design one cannot exclude that flies mark the heated side by an odor that they subsequently avoid during the test. As a final proof for associative learning in the present experiment, flies are trained in one chamber and tested for learning in another, similar one. Handling in the transfer experiment interferes with memory display, even if the fly is returned to the old chamber instead of a new one. Memory can be reactivated, however, by subjecting the fly to an additional brief training (priming), which is too short to establish significant learning in naive flies. For efficient priming, heat has to be applied to the same side as during training in the old chamber. Only then the fly subsequently shows a side preference and avoids the side of the new chamber, which in the old one had been associated with heat. The two chambers are similar but not identical The transfer experiment therefore raises the question as to what the flies use as spatial reference during training and test. In the light, they can be shown to orientate according to visual landmarks associated with the chamber. In complete darkness, where training and memory scores do not differ from those in the light, they are assumed to use a combination of tactile and idiothetic information for orienting.

Animals↗

Effects of systemic and intracerebroventricular administration of mecamylamine, a nicotinic cholinergic antagonist, on spatial memory in rats.

The effects of both systemic and intracerebroventricular administration of mecamylamine, a nicotinic antagonist, were tested on the Morris water maze performance of rats. In experiment 1, mecamylamine (0, 3, and 10 mg/kg, IP) was administered before daily training sessions on the Morris water maze, a task in which rats use environmental cues to learn the location of an invisible escape platform in a large pool of water. The escape latencies of rats given the higher dose of mecamylamine were significantly longer than the latencies of rats given either saline or the peripherally-acting nicotinic antagonist hexamethonium (10 mg/kg). Analysis of search patterns during a free swim trial conducted in the absence of an escape platform confirmed the disruptive effects of the higher dose of mecamylamine. Similar drug effects were not observed when these rats were trained to a visible platform, and mecamylamine did not affect the retrieval of spatial information in well-trained rats. In experiment 2, similar effects were observed with ICV administration of mecamylamine (0, 10, 30, and 100 micrograms). The two higher doses increased escape latencies during the last day of place training and all three doses significantly impaired performance on a free swim. No significant effects were noted on subsequent training to a visible platform, and only the highest dose marginally impaired the retrieval of spatial information in well-trained animals. Thus, mecamylamine appears to impair the acquisition of spatial information in the Morris water maze but does not affect retrieval of previously acquired spatial information at comparable doses.

Animals↗

Passive and active place avoidance as a tool of spatial memory research in rats.

A modified model of the arena described by Bures et al. (Bures J, Fenton AA, Kaminsky Y, Zinyuk L. Place cells and place navigation, Proc. Natl. Acad. Sci. USA. 1997a;94:343-350) was applied to the place learning of adult male rats in two different avoidance paradigms. In the passive avoidance task rats exploring a stationary circular arena had to avoid a 60 degrees sector entering of which was punished by mild footshocks. Intramaze as well as extramaze cues could be used for adequate solution of this task. In the active avoidance paradigm rats were trained to avoid a room frame defined sector (e.g. North-East) of a slowly rotating arena the movement of which forced the animals to rely on extramaze cues and to ignore intramaze information. Rats had to find an active solution of the task since otherwise they were passively transported into the room frame defined punished zone. The suitability of these tasks for testing spatial abilities of rats is discussed.

Animals↗

Effects of the uncompetitive NMDA receptor antagonist memantine on hippocampal long-term potentiation, short-term exploratory modulation and spatial memory in awake, freely moving rats.

Chronic treatment of adult male F-344 rats (9-12 months old) with therapeutically relevant doses of memantine (30 mg/kg/day in chow for > 8 weeks) increased the maintenance of long-term potentiation of field excitatory postsynaptic potentials from perforant path-granule cell hippocampal synapses recorded in the fascia dentata in vivo. In contrast, there was no effect of memantine on baseline synaptic responses or population spikes. Likewise, short-term exploratory modulation of these hippocampal evoked responses was not different between memantine-treated and control rats. Both groups of rats were able to learn the spatial version of the Morris water task equally well, but the memantine-treated group showed a strong tendency to show more selective spatial search patterns in the training quadrant of the water pool during a final probe trial. As such, these studies provide the first electrophysiological evidence that memantine can increase the durability of synaptic plasticity and provide preclinical confirmation of the cognitive improvement seen with memantine in the treatment of demented patients.

Animals↗

Effect of a novel prolyl endopeptidase inhibitor, JTP-4819, on spatial memory and on cholinergic and peptidergic neurons in rats with ibotenate-induced lesions of the nucleus basalis magnocellularis.

We conducted behavioral and neurochemical studies of a novel prolyl endopeptidase inhibitor, (S)2-[[(S)-2-(hydroxyacetyl)-1pyrrolidinyl]carbonyl]-N-(phenylmeth yl)-1-pyrrolidine-carboxamide (JTP-4819), in rats with lesions of the nucleus basalis magnocellularis (NBM-lesioned rats) induced by ibotenate. Administration of JTP-4819 (1 and 3 mg/kg, p.o.), on and after the 8th day, significantly shortened the escape latency in the Morris water maze as compared to the vehicle-treated group. JTP-4819 also significantly increased the path length in the quadrant with the platform removed in the spatial probe trial. Neurochemical studies of brains removed after the Morris water maze task showed that choline acetyltransferase activity in the cerebral cortex, but not the hippocampus, was significantly reduced by NBM lesioning, while there were no changes of muscarinic M1 receptor binding activity detected using [3H]pirenzepine. JTP-4819 had almost no effect on these cholinergic parameters in NBM-lesioned rats. Substance P-like immunoreactivity (LI), thyrotropin-releasing hormone (TRH)-LI, and arginine-vasopressin-LI were not significantly changed in the cerebral cortex and hippocampus of NBM-lesioned rats as compared to sham-operated rats. However, these neuropeptide levels were significantly increased in both brain regions by repeated administration of JTP-4819 (1, 3 and/or 10 mg/kg, p.o.). These results suggest that JTP-4819 ameliorated memory impairment due to NBM lesioning by potentiating SP, TRH and AVPergic neurons secondary to PEP inhibition.

Animals↗

Effects of retention interval length on young and elderly adults' memory for spatial information.

Adult age differences in spatial memory following retention intervals of various lengths were examined in 47 young and 56 elderly subjects who recalled spatial information following either a 3-, 15-, or 30-min retention interval. The elderly adults were significantly less accurate than the young adults following the 30-min retention interval only; there was no statistically significant effect of age at the 3-min and 15-min retention intervals. It is concluded that younger adults experience greater temporal stability of spatial memory than do older adults, and the relevance of the present findings for Craik's environmental support hypothesis is discussed.

Adolescent↗

5-HT1B receptor knock-out mice exhibit increased exploratory activity and enhanced spatial memory performance in the Morris water maze.

In an attempt to characterize the contribution of the 5-HT1B receptor to behavior, 5-HT1B knock-out (KO) mice were subjected to a battery of behavioral paradigms aimed at differentiating various components of cognitive and emotional behaviors. In an object exploration task, wild-type (WT) and 5-HT1B KO mice did not differ in locomotor activity. 5-HT1B KO mice, however, displayed lower thigmotaxis (an index of anxiety) associated with a higher level of object exploratory activity, but no genotype differences were observed in the elevated plus maze. 5-HT1B KO mice also displayed a lack of exploratory habituation. In the spatial version of the Morris water maze, 5-HT1B KO mice showed higher performances in acquisition and transfer test, which was not observed in the visual version of the task. No genotype differences were found in contextual fear conditioning, because both WT and 5-HT1B KO mice were able to remember the context where they had received the aversive stimulus. The deletion of the 5-HT1B receptor, associated with appropriate behavioral paradigms, thus allowed us to dissociate anxiety from response to novelty, and perseverative behavior (lack of habituation) from adaptive behavioral inhibition underlying cognitive flexibility (transfer stage in the water maze). The deletion of the 5-HT1B receptor did not result in significant developmental plasticities for other major 5-HT receptor types but may have influenced other neurotransmission systems. The 5-HT1B receptor may be a key target for serotonin in the modulation of cognitive behavior, particularly in situations involving a high cognitive demand.

Analysis of Variance↗

Effects of concomitant nicotinic and muscarinic blockade on spatial memory disturbance in rats are purely additive: evidence from the Morris water task.

This study reexamined the role played by a concurrent manipulation of nicotinic and muscarinic acetylcholine (ACh) receptors on performance of rats in the Morris water maze. A series of experiments was performed to test decreasing doses of scopolamine, a muscarinic ACh blocker, given concurrently with a fixed dose level of mecamylamine, a nicotinic ACh blocker, down to a subthreshold combination. Both substances were also tested separately. Data were analyzed to distinguish between a summative and a greater than additive (synergistic) effect of the two blocking agents. Our results fully support the important role played by ACh systems on cognitive functions and also show the substantial functional independence of the two ACh receptors in regulating spatial learning processes. In fact, data analysis did not reveal any significant interaction between the two ACh receptor blockers other than their additive effect: the hypothesis of a reciprocal modulation between the two ACh receptors, raised by some authors, cannot be supported for spatial learning mechanisms, at least with regard to the Morris water maze paradigm.

Animals↗

Pigeons' spatial memory: III. Effect of distractors on delayed matching of key location.

The effect of distractors on pigeons' delayed matching of key location was investigated. Baseline trials began with a "ready" stimulus (brief operation of the grain feeder). Then one (randomly chosen) key from a three-by-three matrix was lit briefly as the sample. After a short delay (retention interval) the sample key was lit again along with one of the other eight keys. A peck at the key that had served as the sample (correct comparison) produced grain reinforcement, whereas a peck to the other key (incorrect comparison) produced only the intertrial interval. In Experiment 1, a houselight distractor, presented during either the sample, retention interval, or choice phases of the trial, had little if any effect on accuracy of matching key location. In Experiment 2, one of three types of spatial stimuli was interpolated during the retention interval, or the interval was blank as during baseline trials. The three stimuli were: the sample (correct comparison) location for that trial, the incorrect comparison location for that trial, or one of the seven unused locations for that trial. Relative to blank trials, accuracy improved slightly on sample-interpolated trials, decreased slightly on unused location-interpolated trials, and decreased considerably on incorrect comparison-interpolated trials. In Experiment 3, retention intervals were blank or had one of six types of interpolation: the sample, the incorrect comparison, two presentations of the sample, two presentations of the incorrect comparison, the sample followed by the incorrect comparison, or the incorrect comparison followed by the sample.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

A comparison of the effects of medial prefrontal, cingulate cortex, and cingulum bundle lesions on tests of spatial memory: evidence of a double dissociation between frontal and cingulum bundle contributions.

Rats were trained on an automated delayed nonmatching-to-position (DNMP) task. They then received cytotoxic lesions in either the medial prefrontal cortex (n = 13) or the cingulate and retrosplenial cortices (n = 8), or radiofrequency lesions in either the fornix (n = 6) or the cingulum bundle (n = 8). Twelve animals served as surgical controls. Only the fornical and medial prefrontal lesions disrupted DNMP performance, both groups showing a loss of accuracy and an increase in bias. The rats were then trained on a lever discrimination and reversal task, the medial prefrontal and fornical groups showing evidence of an increase in bias when compared with the cingulate cortex group. Finally, the rats were trained on a forced alternation task in a T-maze. Marked deficits were observed in the fornix and cingulum bundle groups, but the medial prefrontal and cingulate groups were unimpaired. The double dissociation between the effects of the prefrontal and cingulum bundle lesions highlights the very different nature of the two spatial tasks (DNMP and T-maze alternation), even though both involved a nonmatching rule. These findings may reflect the involvement of divergent outputs from the fornix-anterior thalamic pathway. One possibility is that anterior thalamic projections to the medial prefrontal cortex are concerned with processing egocentric information, while anterior thalamic projections to temporal regions via the cingulum bundle are concerned with allocentric information. The results also indicate that the effects of conventional lesions in the cingulate cortex and medial prefrontal cortex may be compromised by additional damage to the cingulum bundle.

Animals↗

Memory for spatial layouts in relation to age and schema typicality.

The hypothesis that prior experience, specifically a knowledge-based schema for typical house layouts, can compensate for age declines in spatial memory was evaluated in 4 experiments. Old and young adults explored and subsequently recalled house layouts presented 1 room at a time on a computer screen. The findings failed to support the compensation hypothesis in that schema-relevant layouts facilitated recall equivalently for the 2 age groups. Violation of a typical house schema had a more negative effect on recall of the older group. Individual differences in spatial visualization ability explained much of the age difference in performance but not the effects of schema manipulations. It was concluded that there is age invariance in the facilitatory effects of relevant prior knowledge on spatial memory but an age-related decrease in the ability to inhibit irrelevant prior knowledge.

Adult↗

Spatial memory in aged rats: population heterogeneity and effect of levocarnitine acetyl.

The existence in a population of aging rats of classes that display a different performance in the Morris water-maze test was investigated by cluster analysis procedure. These classes identified at 18 months of age showed a different response to levocarnitine acetyl and had a different behavioral profile when tested at 25 months of age. These findings demonstrate the need for an alternative interpretation of variability in animal populations as measured by the standard statistical analyses. The data analysis strategy we propose here will allow for the use of variability as a useful source of information.

Acetylcarnitine↗

Symmetry and asymmetry of human spatial memory.

Six experiments investigated the limiting conditions on and the causes of asymmetries in estimates of euclidean distance. Participants estimated distances between locations on recently learned maps or between buildings on their college campus. Estimates between landmarks and neighboring nonlandmarks were often asymmetric, but estimates between other pairs of locations were typically symmetric. These and other results were inconsistent with the predictions of models that attribute asymmetries to stimulus or to retrieval bias. A contextual scaling model of asymmetry is proposed. According to this model, asymmetries in proximity judgments are caused by general principles of human memory and judgment: (a) Stimuli differ in the contexts they establish in working memory and (b) magnitude estimates are scaled by the context in which they are made.

Attention↗

Bacterial alkaloids mitigate seizure-induced hippocampal damage and spatial memory deficits.

Studies of human patients with temporal lobe epilepsy and animal models of epilepsy have established relationships between seizures, excitotoxic hippocampal damage, and memory impairment. We report that bacterial alkaloids, recently shown to mimic actions of neurotrophic factors in cell culture, attenuate seizure-induced damage to hippocampal neurons and memory impairment in adult rats when administered subcutaneously. Intrahippocampal administration of convulsant doses of kainic acid (KA) to adult rats resulted in degeneration of neurons in CA3, CA1, and hilus. Rats administered KA exhibited (24 h later) deficits in performance on both goal latency and probe trial tasks in Morris water maze (MWM) tests of visuospatial memory. Seizure-induced damage to hippocampal neurons was significantly reduced, to varying extents, in rats administered the bacterial alkaloids K252a, K252b, or staurosporine (daily injections of 4 micrograms/kg body weight) prior to KA administration. The KA-induced deficits in MWM goal latency performance were abrogated in rats administered K252a or K252b, and K252a and staurosporine completely prevented seizure-induced impairment on the MWM probe trial. The alkaloids did not suppress electroencephalographic seizure activity, suggesting a dissociation between synchronization of activity and synaptically mediated excitotoxic injury to hippocampal neurons. Each alkaloid caused an increase in levels of protein tyrosine phosphorylation as determined by Western blot analysis of hippocampal tissue. Our data indicate that these bacterial alkaloids have potent antiexcitotoxic activities which may have clinical utility in epilepsy and other disorders that involve excitotoxic damage.

Alkaloids↗