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PubMed1999

Age-related differences in spatial memory: effects of structural and organizational context.

The authors examined effects of structural and organizational spatial context on younger and older adults' memory for an arrangement of dollhouse furniture pieces. For half of the participants, landmark objects (Experiment 1) and a floor plan beneath the array (Experiment 2) served as structural context during study and replacement. Organizational context was varied by grouping items randomly or as 6 rooms in a prototypical house. Two study and replacement trials were given. In Experiment 1, landmark structural cues improved younger adults' performance, whereas both age groups benefited from the floor plan in Experiment 2. In both experiments, positive effects of organizational context and trial occurred. Higher order interactions further revealed that structural and organizational context effects varied in size across trials, suggesting that both age groups used spatial contextual cues more effectively with practice. Implications of these results for current views on cognitive compensation in adulthood are discussed.

Adult↗
PubMed1990

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↗
PubMed1989

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↗
PubMed2001

Behavioral assessment of Alzheimer's transgenic mice following long-term Abeta vaccination: task specificity and correlations between Abeta deposition and spatial memory.

Long-term vaccinations with human beta-amyloid peptide 1-42 (Abeta1-42) have recently been shown to prevent or markedly reduce Abeta deposition in the PDAPP transgenic model of Alzheimer's disease (AD). Using a similar protocol to vaccinate 7.5-month-old APP (Tg2576) and APP+PS1 transgenic mice over an 8-month period, we previously reported modest reductions in brain Abeta deposition at 16 months. In these same mice, Abeta vaccinations had no deleterious behavioral effects and, in fact, benefited the mice by providing partial protection from age-related deficits in spatial working memory in the radial arm water maze task (RAWM) at 15.5 months. By contrast, control-vaccinated transgenic mice exhibited impaired performance throughout the entire RAWM test period at 15.5 months. The present study expands on our initial report by presenting additional behavioral results following long-term Abeta vaccination, as well as correlational analyses between cognitive performance and Abeta deposition in vaccinated animals. We report that 8 months of Abeta vaccinations did not reverse an early-onset balance beam impairment in transgenic mice. Additionally, in Y-maze testing at 16 months, all mice showed comparable spontaneous alternation irrespective of genotype or vaccination status. Strong correlations were nonetheless present between RAWM performance and extent of "compact" Abeta deposition in both the hippocampus and the frontal cortex of vaccinated APP+PS1 mice. Our results suggest that the behavioral protection of long-term Abeta vaccinations is task specific, with preservation of hippocampal-associated working memory tasks most likely to occur. In view of the early short-term memory deficits exhibited by AD patients, Abeta vaccination of presymptomatic AD patients could be an effective therapeutic to protect against such cognitive impairments.

Alzheimer Disease↗
PubMed1992

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↗
PubMed2004

Estrogen alters hippocampal dendritic spine shape and enhances synaptic protein immunoreactivity and spatial memory in female mice.

Estrogen (E) treatment induces axospinous synapses in rat hippocampus in vivo and in cultured hippocampal neurons in vitro. To better explore the molecular mechanisms underlying this phenomenon, we have established a mouse model for E action in the hippocampus by using Golgi impregnation to examine hippocampal dendritic spine morphology, radioimmunocytochemistry (RICC) and silver-enhanced immunocytochemistry to examine expression levels of synaptic protein markers, and hippocampal-dependent object-placement memory as a behavioral readout for the actions of E. In ovariectomized mice of several strains and F(1) hybrids, the total dendritic spine density on neurons in the CA1 region was not enhanced by E treatment, a finding that differs from that in the female rat. E treatment of ovariectomized C57BL/6J mice, however, caused an increase in the number of spines with mushroom shapes. By RICC and silver-enhanced immunocytochemistry, we found that the immunoreactivity of postsynaptic markers (PSD95 and spinophilin) and a presynaptic marker (syntaxin) were enhanced by E treatment throughout all fields of the dorsal hippocampus. In the object-placement tests, E treatment enhanced performance of object placement, a spatial episodic memory task. Taken together, the morphology and RICC results suggest a previously uncharacterized role of E in synaptic structural plasticity that may be interpreted as a facilitation of the spine-maturation process and may be associated with enhancement of hippocampal-dependent memory.

Animals↗
PubMed1999

Sensitivity to cholinergic drug treatments of aged rats with variable degrees of spatial memory impairment.

As a first step, the present experiment aimed at characterizing learning and memory capabilities, as well as some motor and sensorimotor faculties, in aged (24-26.5 months) Long-Evans female rats. As a second step, a psychopharmacological approach was undertaken in order to examine the sensitivity of aged rats to muscarinic blockade and to cholinomimetic treatments. Young adult (3-5.5 months) and aged rats were tested for beam-walking performance, locomotor activity in the home cage and an open field, and spatial learning/memory performance in a water maze and a radial maze. Spontaneous alternation rates were assessed in a T-maze. Statistical analysis discriminated between aged rats showing moderate impairment (AMI) and those showing severe impairment (ASI) in the water maze test. Beside their different degrees of impairment in the water maze, AMI and ASI rats were similarly (no significant difference) impaired in beam-walking capabilities, home cage activity and radial maze performance. In the spontaneous alternation task aged rats were not impaired and, in the open-field test, AMI rats were hypoactive, but not as much as ASI rats. Neither of the cognitive deficits was correlated with a locomotor or a sensorimotor variable, or with the body weight. When tested in the radial maze, a low dose of scopolamine (0.1 mg/kg i.p.) produced memory impairments which were significant in AMI and ASI rats, but not in young rats. Combined injections of scopolamine and physostigmine (0.05 and 0.1 mg/kg) or tacrine (THA, 3 mg/kg) showed physostigmine (0.1 mg/kg) to compensate for the scopolamine-induced impairments only in AMI rats. whereas THA was efficient in both AMI and ASI rats. The results indicate: (i) that rats with different degrees of spatial memory impairment in the water maze are similarly hypersensitive to muscarinic blockade when tested in a radial maze test; and (ii) that under the influence of a dose of scopolamine which is subamnesic in young rats, aged rats respond to anticholinesterase treatments according to the level of performance achieved in the water maze: moderately impaired rats are sensitive to both physostigmine and THA, whereas more severely impaired rats are sensitive only to THA.

Aging↗
PubMed1995

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↗
PubMed2002

A spatial memory task appropriate for electrophysiological recordings.

We developed a novel method for assessing spatial learning that is compatible with the requirements of electrophysiological recording of multiple single neurons. The behavioral task utilized a rectangular track with 8 reward boxes of which a subset contained available food (bait). Errors were scored whenever the rat investigated a non-baited box location (commission), failed to investigate a baited box location (omission), or hesitated in front of a non-baited box location (hesitation). Several controls encouraged the animal to solve the task through allocentric cues rather than through procedural strategies or simple local cue pairing. The learning curve for this task (3-5 d to criterion) was comparable to that of other spatial learning tasks when adequately motivated. The types of errors varied as the animal learned the task. Unlike other spatial learning tasks, the multi-box track allows many repeated samples of the same spatial coordinates within a short period of time to allow, for example, reliable determination of place fields while recording from hippocampal cells. Multiple trials per session also allow for high intensity training important for many learning assessments such as the timing and type of sleep involved in learning and memory.

Analysis of Variance↗
PubMed2003

Head-only exposure to GSM 900-MHz electromagnetic fields does not alter rat's memory in spatial and non-spatial tasks.

Over the last decade, exposure to high frequency (2450 MHz) electromagnetic fields (EMFs) has been found to induce performance deficit in rodents in spatial memory tasks. As concern was expressed about potential biological effects of mobile communication microwaves, studies testing the effects of signals such as GSM were required. In a previous study, using head-only exposure to 900 MHz GSM EMF, we could not demonstrate any behavioural deficit in two simple learning tasks. The present study aimed at extending these results with more complex spatial learning tasks and a non-spatial task. In a first experiment, rats were trained in a radial-arm maze with a 10-s confinement between each visited arm. In a second experiment, a 15-min intra-trial delay was introduced after four visited arms. In a third experiment, non-spatial memory was tested in an object recognition task. In all experiments, performance of the head-only exposed rats (1 and 3.5 W/kg) was compared with that of sham and control rats. In the first experiment, a slightly improved performance was found after 3.5 W/kg exposure, a result that was not observed in the delay-task. In the third experiment, although some effects on exploratory activity were found, recognition memory was unaffected in exposed rats. Altogether, this set of experiments provides no evidence indicating that spatial and non-spatial memory can be affected by a 45-min head-only exposure to 900 MHz GSM EMF.

Animals↗
PubMed1991

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↗
PubMedDate not supplied

[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↗
PubMed1975

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↗
PubMed2003

Effects of gaze shifts on maintenance of spatial memory in macaque frontal eye field.

The activity of 91 neurons in the frontal eye fields (FEFs) of two macaque monkeys was recorded while the animals performed a delayed spatial match-to-sample task. During the delay, the animals were required to shift their gaze to one of four eccentric locations. Neuronal activity during the delay was analyzed for sensitivity to cue location and eye position. One-third of the neurons showed significant delay activity selective for cue location, whereas slightly more than one-half of the neurons showed significant modulation of delay activity when the gaze was shifted to an eccentric location. Despite this modulation, the neurons continued to signal their preferred cue location during most of the delay. However, after recentering saccades, the memory signal was temporarily abolished and then reemerged over a period of few hundred milliseconds. This is consistent with the idea that spatial working memory is buffered outside of the FEF. For most neurons, delay activity tended to increase when the gaze was shifted away from the preferred location and to decrease when the gaze was shifted toward the preferred location. This pattern of modulation is consistent with a vector subtraction mechanism that allows for the superposition of multiple saccade plans.

Animals↗
PubMed1990

[Pharmacological correction of ketamine-impaired spatial memory of rats].

Ketamine in dose 10 mg/kg increased the number of erroneous choices of rats with spatial strategy and didn't effect searching accuracy of rats with non-spatial strategy in 8-arm radial maze. Ketamine in doses 1 and 5 mg/kg disrupted rat short-term memory in delayed response reaction. Physostigmine and aspartic acid, but not haloperidol, diminished ketamine amnesia, therefore ketamine impaired the interaction of cholinergic and glutamate/aspartatergic neurons of hippocampal areas.

Amnesia↗
PubMed1988

Transplantation of embryonic ventral forebrain grafts to the neocortex of rats with bilateral lesions of nucleus basalis magnocellularis ameliorates a lesion-induced deficit in spatial memory.

Embryonic ventral forebrain grafts containing developing cholinergic cells were transplanted to the neocortex of rats with bilateral quisqualic acid lesions of the nucleus basalis magnocellularis. A lesion-induced deficit on performance of a spatial alternation test of memory was reduced by such transplants. When the same animals were treated with the acetylcholinesterase inhibitor physostigmine (0.05 mg/kg), however, performance on the behavioral task was not further promoted, and therefore, under these conditions, the cholinergic cortical transplants appear not to be subject to modulation by anticholinesterase drugs.

Acetylcholinesterase↗
PubMed2001

Chronic cerebral hypoperfusion in the rat enhances age-related deficits in spatial memory.

Ten-week old rats were subjected to chronic mild hypoperfusion by a permanent bilateral ligation of common carotid arteries (2VO). Animals were repeatedly tested in 8-arm radial maze at 1 week, 3, 10 and 16 months after the surgery to investigate long term effects of 2VO on spatial learning and memory. Occluded rats showed initially mild deficits in reference (RM) and working (WM) memory that were progressing with time and reached level of marked differences 16 months after the surgery. Advanced age significantly influenced cognitive function in both groups but the observed deterioration was more pronounced in 2VO animals. We suggest that the long-lasting reduction of cerebral blood flow combined with ageing can result in the enhanced cognitive impairment of aged individuals.

Aging↗