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Working memory tasks in five-choice operant chambers: use of relative and absolute spatial memories.

Rats were trained to nose poke into illuminated holes to perform 1 of 2 different spatial working memory tasks (relative recency or reward history) in a 5-choice operant chamber. A series of experiments indicated that choice accuracy on both tasks depended on (a) the holes' spatial separation, and (b) their relative rather than absolute positions. The results suggest that accurate choice depended on using a motor mediation strategy to turn, so as to encounter the target (correct) hole before encountering the alternative (wrong) hole. The drugs administered to the rats, d-amphetamine, scopolamine, and CGP-37849 impaired choice accuracy on these tasks, even though task performance had not appeared to depend on explicit memory for the sample responses. This suggests that parallel drug effects obtained on other operant matching- or nonmatching-to-position tasks may not have reflected truly amnesic effects of the drug treatments.

2-Amino-5-phosphonovalerate↗

Effects of melatonin on oxidative stress and spatial memory impairment induced by acute ethanol treatment in rats.

Melatonin has recently been suggested as an antioxidant that may protect neurons from oxidative stress. Acute ethanol administration produces both lipid peroxidation as an indicator of oxidative stress in the brain and impairs water-maze performance in spatial learning and memory tasks. The present study investigated the effect of melatonin against ethanol-induced oxidative stress and spatial memory impairment. The Morris water maze was used to evaluate the cognitive functions of rats. Thiobarbituric acid reactive substances (TBARS), which are the indicators of lipid peroxidation, and the activities of antioxidative enzymes (glutathione peroxidase and superoxide dismutase) were measured in the rat hippocampus and prefrontal cortex which form interconnected neural circuits for spatial memory. Acute administration of ethanol significantly increased TBARS levels in the hippocampus. Combined melatonin-ethanol treatment caused a significant increase in glutathione peroxidase activities and a significant decrease of TBARS in the rat hippocampus. In the prefrontal cortex, there was only a significant decrease of TBARS levels in the combined melatonin-ethanol receiving group as compared to the ethanol-treated group. Melatonin did not affect the impairment of spatial memory due to acute ethanol exposure, but melatonin alone had a positive effect on water maze performances. Our study demonstrated that melatonin decreased ethanol-induced lipid peroxidation and increased glutathione peroxidase activity in the rat hippocampus.

Animals↗

Allocentric spatial memory activation of the hippocampal formation measured with fMRI.

Hippocampal activation was investigated, comparing allocentric and egocentric spatial memory. Healthy participants were immersed in a virtual reality circular arena, with pattern-rendered walls. In a viewpoint-independent task, they moved toward a pole, which was then removed. They were relocated to another position and had to move to the prior location of the pole. For viewpoint-dependent memory, the participants were not moved to a new starting point, but the patterns were rotated to prevent them from indicating the final position. Hippocampal and parahippocampal activation were found in the viewpoint-independent memory encoding phase. Viewpoint-dependent memory did not result in such activation. These results suggest differential activation of the hippocampal formation during allocentric encoding, in partial support of the spatial mapping hypothesis as applied to humans.

Adult↗

Role of nitric oxide in the effect of aging on spatial memory in rats.

Since there is evidence that nitric oxide (NO) plays an important role as a diffusible messenger in learning and memory, we examined the role played by NO in the effect of aging on spatial memory in rats. The performance of aged rats (30 months old) in a radial-arm maze task was significantly impaired compared to that of adult rats (3 months old). The number of neurons containing NADPH-diaphorase (NADPH-d) reactivity in the cerebral cortex and striatum of aged rats was significantly less than that in the adult rats. The daily administration of NG-nitro-L-arginine methyl ester (L-NAME; 10-60 mg/kg, i.p.) resulted in a dose-dependent impairment of acquisition in the radial-arm maze task, while it failed to affect previously acquired performance, i.e., retention, in the adult rats. The content of 5-hydroxyindoleacetic acid in the hippocampus and of 3,4-dihydroxyphenylacetic acid in the striatum was significantly decreased and increased, respectively, in the L-NAME (60 mg/kg/day)-treated adult rats compared with that in controls. These findings demonstrate that NO production in the brain may be decreased in aged rats, suggesting that this alteration may be involved in memory processes, especially in the acquisition, but not in the retention, of spatial learning in rats, and further, that endogenous NO may be involved in the regulation of dopamine and 5-hydroxytryptamine metabolism.

Aging↗

Nerve growth factor reverses spatial memory impairments in aged rats.

Aged rats, displaying impairments in spatial learning and memory associated with marked cellular atrophy of forebrain cholinergic neurons, received intracerebroventricular infusions of the neurotrophin nerve growth factor (NGF), or vehicle. During the 4-week infusion period rats receiving NGF showed improved acquisition and retention of spatial memory. With NGF this was accompanied by a significant reduction in cholinergic neuron atrophy in both septum, nucleus basalis and striatum. The cause of learning and memory deficits associated with ageing is not known. In the present paper we show that learning and memory deficits in aged rats can be reversed by NGF.

Acetylcholinesterase↗

Development of memory for pattern and path: further evidence for the fractionation of visuo-spatial memory.

Evidence from a number of sources now suggests that the visuo-spatial sketchpad (VSSP) of working memory may be composed of two subsystems: one for maintaining visual information and the other for spatial information. In this paper we present three experiments that examine this fractionation using a developmental approach. In Experiment 1, 5-, 8-, and 10-year old children were presented with a visuo-spatial working memory task (the matrices task) with two presentation formats (static and dynamic). A developmental dissociation in performance was found for the static and dynamic conditions of both tasks, suggesting that the activation of separable subsystems of the VSSP is dependent upon a static/dynamic distinction in information content rather than a visual/spatial one. A highly similar pattern of performance was found for a mazes task with static and dynamic formats. However, one strategic activity, the use of simple verbal recoding, may also have been responsible for the observed pattern of performance in the matrices task. In Experiments 2 and 3 this was investigated using concurrent articulatory suppression. No evidence to support this notion was found, and it is therefore proposed that static and dynamic visuo-spatial information is maintained in working memory by separable subcomponents of the VSSP.

Child↗

Retrograde amnesia: neither partial nor complete hippocampal lesions in rats result in preferential sparing of remote spatial memory, even after reminding.

Many lesion experiments have provided evidence that the hippocampus plays a time-limited role in memory, consistent with the operation of a systems-level memory consolidation process during which lasting neocortical memory traces become established [see Squire, L. R., Clark, R. E., & Knowlton, B. J. (2001). Retrograde amnesia. Hippocampus 11, 50]. However, large lesions of the hippocampus at different time intervals after acquisition of a watermaze spatial reference memory task have consistently resulted in temporally ungraded retrograde amnesia [Bolhuis, J. J., Stewart, C. A., Forrest, E. M. (1994). Retrograde amnesia and memory reactivation in rats with ibotenate lesions to the hippocampus or subiculum. Quarterly Journal of Experimental Psychology 47B, 129; Mumby, D. G., Astur, R. S., Weisend, M. P., Sutherland, R. J. (1999). Retrograde amnesia and selective damage to the hippocampal formation: memory for places and object discriminations. Behavioural Brain Research 106, 97; Sutherland, R. J., Weisend, M. P., Mumby, D., Astur, R. S., Hanlon, F. M., et al. (2001). Retrograde amnesia after hippocampal damage: recent vs. remote memories in two tasks. Hippocampus 11, 27]. It is possible that spatial memories acquired during such a task remain permanently dependent on the hippocampus, that chance performance may reflect a failure to access memory traces that are initially unexpressed but still present, or that graded retrograde amnesia for spatial information might only be observed following partial hippocampal lesions. This study examined the retrograde memory impairments of rats that received either partial or complete lesions of the hippocampus either 1-2 days, or 6 weeks after training in a watermaze reference memory task. Memory retention was assessed using a novel 'reminding' procedure consisting of a series of rewarded probe trials, allowing the measurement of both free recall and memory reactivation. Rats with complete hippocampal lesions exhibited stable, temporally ungraded retrograde amnesia, and could not be reminded of the correct location. Partially lesioned rats could be reminded of a recently learned platform location, but no recovery of remote memory was observed. These results offer no support for hippocampus-dependent consolidation of allocentric spatial information, and suggest that the hippocampus can play a long-lasting role in spatial memory. The nature of this role--in the storage, retrieval, or expression of memory--is discussed.

Amnesia, Retrograde↗

Time-dependent relationship between the dorsal hippocampus and the prefrontal cortex in spatial memory.

The prefrontal cortex and the dorsal hippocampus have been studied extensively for their significant roles in spatial working memory. A possible time-dependent functional relationship between the prefrontal cortex and the dorsal hippocampus in spatial working memory was tested. A combined lesion and pharmacological inactivation technique targeting both the dorsal hippocampus and the medial prefrontal cortex was used (i.e., axon-sparing lesions of the dorsal hippocampus combined with reversible inactivation of the medial prefrontal cortex, or vice versa, within a subject). A delayed nonmatching-to-place task on a radial eight-arm maze with short-term (i.e., 10 sec) versus intermediate-term (i.e., 5 min) delays was used as a behavioral paradigm. Here we report that the dorsal hippocampus and the medial prefrontal cortex process short-term spatial memory in parallel, serving as a compensatory mechanism for each other. The role of the dorsal hippocampus, however, becomes highlighted as the time-window for memory (i.e., delay) shifts from short-term to a delay period (i.e., intermediate-term) exceeding the short-term range. The results indicate that the time window of memory is a key factor in dissociating multiple memory systems.

Animals↗

Experience-dependent changes in the hippocampus of domestic chicks: a model for spatial memory.

In the domestic chicken, providing visual barriers for a brief period early in life has been found to improve spatial memory [R. Freire et al. (2004)Animal Behaviour, 67, 141-150]. In the present study we compared the structure of neurons in the hippocampus and neostriatum in chicks reared with or without visual barriers. From 8 to 16 days of age, chicks were reared in pens either with two wooden screens (Treatment E) or with no screens (Treatment C). At 16 days of age, chicks were anaesthetized, perfused intracardially and brain samples collected and stained using a Golgi-Cox technique. Morphometric analysis revealed that the multipolar projection neurons of Treatment E chicks had longer dendrites (ANOVA, F(1,14) = 7.4, P < 0.05) and had more spines per 20 micro m of dendrite (SLD; ANOVA, F(1,14) = 10.6, P < 0.01) than those of Treatment C chicks. By contrast, no evidence was found that rearing treatment differentially influences dendrite length or SLD in the neostriatum, suggesting that the above environment-induced changes may be specific to the hippocampus. Multipolar projection neuron dendrites of the right hemisphere were longer (ANOVA, F(1,14) = 36.4, P < 0.0001) and had more spines (ANOVA, F(1,14) = 8.8, P < 0.05) than dendrites of the left hemisphere, supporting previous findings that the right hemisphere of chickens is predominantly involved in spatial processing. We conclude that the chicken provides a useful model for the study of developmental plasticity in brain and behaviour, partly because the possibility of rearing chicks in isolation and imprinting them on an artificial object provides a means of accurately manipulating early experience.

Animals↗

Visual distraction and visuo-spatial memory: a sandwich effect.

The functional characteristics of visuo-spatial serial memory and its sensitivity to irrelevant visual information are examined in the present study, through the investigation of the sandwich effect (e.g., Hitch, 1975). The memory task was one of serial recall for the position of a sequence of seven spatially and temporally separated dots. The presence of irrelevant dots interpolated with to-be-remembered dots affected performance over most serial positions (Experiment 1) but that effect was significantly reduced when the interpolated dots were distinct from the to-be-remembered dots by colour and shape (Experiment 2). Parallels are made between verbal and spatial serial memory, and the reduction of the sandwich effect is discussed in terms of the contribution of perceptual organisation and attentional factors in short-term memory.

Analysis of Variance↗

Effects of disrupting the cholinergic system on short-term spatial memory in rats.

The effects of disrupting the muscarinic or nicotinic systems on short-term spatial memory were investigated using a delayed matching to position (DMTP) procedure. Rats were trained on the DMTP until stability and then divided into two groups: one group was implanted with an indwelling cannula aimed at the lateral ventricle. The cannulated group received injections of selective muscarinic antagonists (pirenzepine, M1; AFDX 116, M2; UH-AH 37, M1/M3) or hemicholinium-3 (a choline uptake inhibitor). The remaining animals were treated with conventional muscarinic antagonists (scopolamine, methyl scopolamine) or nicotinic channel blockers (mecamylamine, hexamethonium). Scopolamine, methyl scopolamine and UH-AH 37 disrupted all performance parameters in a non-specific but dose related manner. Pirenzepine disrupted accuracy in a delay, but not dose dependent manner, and exerted no other negative effects on performance. Hemicholinium-3-induced performance deficits showed some elements of effects seen following pirenzepine and scopolamine (delay dependent effects on accuracy, some negative effects on other motoric aspects of performance). AFDX 116 and hexamethonium had no significant effects on performance with respect to control. Mecamylamine reduced accuracy and increased response latencies at the highest dose tested. These data indicate that muscarinic antagonists are more effective at disrupting mnemonic performance than nicotinic blockers, and moreover, that distinct muscarinic receptors may have differential effects on cognitive performance.

Animals↗

A long-acting cholinesterase inhibitor reverses spatial memory deficits in mice.

The effects of the long-acting acetylcholinesterase (AChE) inhibitor, galanthamine, on spatial memory were investigated in mice. Mice received ibotenic acid or sham lesions to the nucleus basalis magnocellularis (nBM). Groups of nBM-lesioned and control mice were then trained on a modified Morris swim maze task. Each mouse was first placed on a platform and then into quadrants of the swim tank in a random order. Time required to find the hidden platform was measured. In different phases of testing, the animal had to find a platform that either remained in the same quadrant (reference memory component) or was moved daily (working memory component). The nBM-lesioned mice took significantly longer to find the platform as compared to controls on the working, but not on the reference, memory component of the task. Galanthamine (5.0 mg/kg, IP), given 3.5 hours before testing, improved performance on the working memory task in nBM-lesioned mice by 70% and strikingly impaired performance in controls. Galanthamine's ability to reverse cognitive deficits induced by nBM lesions and its comparatively long half-life suggest that it may be effective in treating the central cholinergic deficits in Alzheimer's disease patients.

Animals↗

Age differences in spatial memory in a virtual environment navigation task.

The use of virtual environment (VE) technology to assess spatial navigation in humans has become increasingly common and provides an opportunity to quantify age-related deficits in human spatial navigation and promote a comparative approach to the neuroscience of cognitive aging. The purpose of the present study was to assess age differences in navigational behavior in a VE and to examine the relationship between this navigational measure and other more traditional measures of cognitive aging. Following pre-training, participants were confronted with a VE spatial learning task and completed a battery of cognitive tests. The VE consisted of a richly textured series of interconnected hallways, some leading to dead ends and others leading to a designated goal location in the environment. Compared to younger participants, older volunteers took longer to solve each trial, traversed a longer distance, and made significantly more spatial memory errors. After 5 learning trials, 86% of young and 24% of elderly volunteers were able to locate the goal without error. Performance on the VE navigation task was positively correlated with measures of mental rotation and verbal and visual memory.

Adult↗

Species differences in spatial memory among Clark's nutcrackers, scrub jays, and pigeons.

An operant nonmatching to sample procedure was used to compare the spatial memory abilities of 3 avian species. A trial consisted of the presentation of a spatially defined sample, a delay interval, and a 2-choice test during which the correct location was the new location. A single spatial location served as the sample in Experiment 1. The delay interval was manipulated using a titration procedure. In Experiment 2, 1, 2, or 3 sequentially illuminated locations served as the sample. The delay was 1 of 4 predetermined intervals. In Experiment 3, sample presentation was the same as Experiment 2, but the delay interval was titrated. In all of the experiments, the performance of nutcrackers was consistently better than the performance of scrub jays and pigeons (Experiment 1) and was correlated with differences in their foraging ecology.

Animals↗

Pigeons' spatial memory: factors affecting delayed matching of key location.

The delayed-matching-to-sample procedure was modified to study pigeons' spatial memory. Nine pecking keys, arranged as a three-by-three matrix, served as the spatial cues. Trials began with a brief "ready" stimulus (dimming of the houselight). Then a randomly chosen key was lit briefly as a sample. After a short delay 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 produced grain reinforcement, where as a peck to the other key produced only the intertrial interval. After delayed matching of key location was learned, the effects of sample and delay duration, number of keys illuminated as sample and comparisons, and organization of three-key samples were studied. Matching accuracy decreased as sample duration decreased, delay increased, the number of locations serving as samples increased, the number and proximity of comparisons increased, and when the three-key samples were "discontinuous" rather than "lines".

Animals↗

On the behavioral significance of head direction cells: neural and behavioral dynamics during spatial memory tasks.

Current theories assume that rats use the directional information reflected by head direction (HD) cells when performing spatial tasks. This assumption was assessed by monitoring anterior thalamic HD cell activity and relating it to the subject's behavioral response on 2 spatial memory tasks that tested either reference memory or working memory. In both tasks, there was a significant number of trials where there was not a tight coupling between the preferred firing direction of HD cells and the direction of the behavioral response. In addition, it was possible to intentionally change the preferred direction of HD cells without affecting performance accuracy. An additional experiment showed that manipulations that affected internal, but not external, cues impaired performance on the reference memory task. These findings suggest that HD cell activity was not consistently guiding the subjects' behavior on these 2 spatial tasks.

Animals↗

Raphe cells grafted into the hippocampus can ameliorate spatial memory deficits in rats with combined serotonergic/cholinergic deficiencies.

The ability of embryonic raphe cells grafted into the hippocampus to restore spatial learning ability was tested in rats with combined serotonergic/cholinergic deficits. Embryonic raphe cells (E14) were transplanted into the hippocampus of serotonin-depleted rats. Two to 3 months after transplantation, control, lesioned and grafted rats were tested in a spatial memory task (a water maze) with and without the addition of atropine. All 3 groups could negotiate the water maze equally well, in non-drug conditions. The injection of atropine caused a severe disruption of performance only in the serotonin depleted rats. The presence of an active serotonergic graft was examined in the intact rat hippocampus using the serotonin releasing drug fenfluramine (FFA). A pronounced depression of hippocampal EEG was observed in control and grafted but not in lesioned rats 15 min after the injection of FFA. These results suggest the involvement of serotonin in cognitive functions in the rat. Furthermore, it is suggested that an interaction between serotonergic and cholinergic neurotransmission occurs in the hippocampus.

Animals↗

Humans with hippocampus damage display severe spatial memory impairments in a virtual Morris water task.

For nonhumans, it has been shown that the hippocampus (HPC) is critical for spatial memory. We tested patients with unilateral HPC resections on a virtual analogue of a classic spatial task to assess HPC functioning in nonhumans: the Morris water task. We found that when humans are required to use spatial cues to navigate to a hidden escape platform in a pool, patients with HPC resections display severe impairments in spatial navigation relative to age-matched controls and age-matched patients who have had extra-HPC resections. This effect occurred for every patient tested and was evident regardless of side of surgery. Hence, it is apparent across species and irrespective of which hemisphere is damaged that the human HPC is critical for spatial/relational memory.

Brain Damage, Chronic↗