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Spatial memory and stereotypic behaviour of animals in radial arm mazes.

The symmetric radial arm maze, described by Olton in 1976, has developed into an important tool for the study of spatial memory. In a typical test an animal is placed in the centre of the maze, which contains some small piece of food at the end of each arm. The sampling behaviour of the animal is then recorded. In such studies the score (number of choices of arms which still contain food) of the animal is normally compared with the score of an imaginary animal which changes arms entirely at random. In a new method of analysis the non-random score of the animal is split into two parts, one depending on memory and one on stereotypic choice behaviour. Even mild departures from randomness are shown to alter considerably the expected 'random' score in an eight-armed maze. The part of the score claimed to depend on memory was shown to increase when the animals learn to search the maze, the stereotypic part did not. The general effect from stereotypic choice behaviour is shown to result, in most animals, in an increase in the total score. In an eight-armed maze this increase may amount to more than 20% of the total non-random score, even in a well-trained animal. The effect is less pronounced in mazes with 16 arms. It has been proposed that hippocampal lesions produce a stereotypic behaviour. We propose, based on our analysis, that the stereotypic behaviour is not produced but revealed by hippocampal lesions which destroy almost completely the memory-guided behaviour masking the stereotypic behaviour in the intact animal.

Animals↗

The hippocampus mediates glucocorticoid-induced impairment of spatial memory retrieval: dependence on the basolateral amygdala.

Previous studies have indicated that stress-activated glucocorticoid hormones induce temporary memory retrieval impairment. The present study examined whether adrenal steroid receptors in the hippocampus mediate such glucocorticoid effects on spatial memory retrieval. The specific glucocorticoid receptor (GR) agonist 11beta, 17beta-dihydroxy-6,21-dimethyl-17alpha-pregna-4,6-trien-20yn-3-one (RU 28362; 5 or 15 ng) infused into the hippocampus of male Sprague-Dawley rats 60 min before water-maze retention testing, 24 h after training, dose-dependently impaired probe-trial retention performance, as assessed both by time spent in the training quadrant and initial latency to cross the platform location. The GR agonist did not affect circulating corticosterone levels immediately after the probe trial, indicating that RU 28362 infusions did not influence retention by altering glucocorticoid feedback mechanisms. As infusions of the GR agonist into the hippocampus 60 min before training did not influence water-maze acquisition or immediate recall, the findings indicated that the GR agonist-induced retention impairment was induced selectively by an influence on information retrieval. In contrast, pretest infusions of the GR agonist administered into the basolateral complex of the amygdala (BLA; 2 or 6 ng) did not alter retention performance in the water maze. However, N-methyl-d-aspartate-induced lesions of the BLA, made 1 week before training, blocked the memory retrieval impairment induced by intrahippocampal infusions of RU 28362 given 60 min before the retention test. These findings indicate that the effects of glucocorticoids on retrieval of long-term spatial memory depend on the hippocampus and, additionally, that neuronal input from the BLA is critical in enabling hippocampal glucocorticoid effects on memory retrieval.

Adrenal Cortex Hormones↗

Brain areas involved in spatial working memory.

Spatial working memory entails the ability to keep spatial information active in working memory over a short period of time. To study the areas of the brain that are involved in spatial working memory, a group of stroke patients was tested with a spatial search task. Patients and healthy controls were asked to search through a number of boxes shown at different locations on a touch-sensitive computer screen in order to find a target object. In subsequent trials, new target objects were hidden in boxes that were previously empty. Within-search errors were made if a participant returned to an already searched box; between-search errors occurred if a participant returned to a box that was already known to contain a target item. The use of a strategy to remember the locations of the target objects was calculated as well. Damage to the right posterior parietal and right dorsolateral prefrontal cortex impaired the ability to keep spatial information 'on-line', as was indicated by performance on the Corsi Block-Tapping task and the within-search errors. Moreover, patients with damage to the right posterior parietal cortex, the right dorsolateral prefrontal cortex and the hippocampal formation bilaterally made more between-search errors, indicating the importance of these areas in maintaining spatial information in working memory over an extended time period.

Brain↗

Effect of excitotoxic lesions of rat medial prefrontal cortex on spatial memory.

The involvement of medial prefrontal cortex (mPFC) in spatial learning was examined in two memory tasks using spatial components, the Morris water maze and the three-panel runway. Using the Morris water maze task, with an invisible platform, the effects of NMDA mPFC lesions were assessed in a procedure reflecting spatial learning and memory, including a spatial reversal. In the three-panel runway, a delayed matching-to-position procedure was used in which rats were required to find food at the end of the runway after passing through one of three panel gates set into four barriers spaced equally apart along the maze. In addition, mPFC lesions were assessed behaviorally in two behavioral tests known to be sensitive to mPFC dysfunction: the food hoarding paradigm and spontaneous locomotion in the open field. Consistent with the documented effects of mPFC damage, NMDA mPFC lesions impaired food hoarding behavior and increased spontaneous exploratory locomotion. In the Morris water maze and the three-panel runway, mPFC-lesioned rats showed relatively few effects, supporting the conclusion that the damage inflicted to the mPFC had no consequence for the processing of spatial information. However, mPFC lesioned animals showed slower acquisition during both the training trial in the three-panel runway and the reversal training in the Morris water maze. These results suggest that spatial memory did not depend on mPFC integrity in the Morris water maze and the three-panel runway experiments, and address the issue of deficits induced by mPFC lesions in memory tasks dependent on non-mnemonic processes such as attentional processes and/or a reduced behavioral flexibility to environmental changes.

Animals↗

Galanin regulates spatial memory but not visual recognition memory or synaptic plasticity in perirhinal cortex.

It has previously been shown that the neuropeptide galanin plays a role in the age-dependent regulation of hippocampal synaptic plasticity and spatial memory. Here, we further extend these studies by demonstrating that galanin knockout mice also have deficits in an object-in-place spatial memory task. In contrast however, there is no deficit in single item object recognition memory, a memory that depends on perirhinal cortex. Furthermore, in perirhinal cortex slices there are no differences in activity-dependent long-term potentiation or depotentiation, nor in muscarinic receptor-dependent long-term depression between galanin knockout mice and wild-type litter-mates. Therefore, these results suggest that galanin has a differential role in hippocampal-dependent and perirhinal cortex-dependent memory.

Animals↗

Spatial memory, navigation and dance behaviour in Apis mellifera.

Navigation and dance communication in Apis mellifera have been extensively studied on the level of sensory processing, but the structure and content of the spatial memory underlying such phenomena have yet to be addressed. Here we survey new findings indicating that the memory used by bees to navigate within the range of their orientation flights is much more complex than hitherto thought. It appears to allow them to decide between at least two goals in the field, and to steer towards them over considerable distances. Two models concerning the structure of bees' spatial memory are developed from new empirical evidence. The first one relies on the integration of at least two flight vectors, while the second assumes the existence of a 'functional' map based on the information available on-site. These findings also raise questions about the process of encoding and decoding information in the context of the waggle dance. We review published data and recent evidence indicating that memories of topographical features might also be involved in dance communication, and point out what needs to be addressed to elucidate the corresponding memory demands. The flight paths of recruited bees can now be traced by means of radar techniques, and thus tools are available to tackle these questions.

Animal Communication↗

Cooperation between the hippocampus and the entorhinal cortex in spatial memory: a disconnection study.

It has been recently shown that lesions of parahippocampal areas including the entorhinal cortex do not disrupt place learning in the water maze, suggesting that the hippocampo-cortical circuitry is not important for spatial memory [Burwell RD, Saddoris MP, Bucci DJ, Wiig KA. Corticohippocampal contributions to spatial and contextual learning. J Neurosci 2004;24:3826-36]. The aim of the present study was to tax more directly the cooperation between the hippocampus and entorhinal cortex in two different spatial tasks, a place navigation task and a spontaneous object exploration task, using a disconnection procedure. Damaging the entorhinal-hippocampal system induced impairments in the two tasks but only in the spatial object exploration task rats with contralateral lesions displayed a greater deficit than rats with ipsilateral lesions. The results suggest that the cooperation between the hippocampus and the entorhinal cortex is modulated by the nature of the task and the cognitive processes involved in formation of spatial memory.

Animals↗

The neurosteroid pregnenolone sulfate infused into the nucleus basalis increases both acetylcholine release in the frontal cortex or amygdala and spatial memory.

The effects of an infusion (5 ng) of the neurosteroid pregnenolone sulfate into the nucleus basalis magnocellularis on acetylcholine release in the frontoparietal cortex and basolateral amygdala were evaluated during the 130 min post-injection in male Sprague-Dawley rats using in vivo microdialysis coupled "on line" with high performance liquid chromatography detection. One week later, the same animals were tested for spatial memory after another infusion of pregnenolone sulfate (5 ng) into the nucleus basalis. Results show that pregnenolone sulfate enhanced acetylcholine release by more than 50% of baseline concentrations in the two structures relative to a control injection. The duration of this effect was longer in cortex (130 min) than in amygdala (30 min). Furthermore, pregnenolone sulfate improved memory performance in a task based upon spatial recognition of a familiar environment. A significant positive correlation (r=0.49) was found between the recognition score in the spatial memory test and the levels of acetylcholine release in the frontoparietal cortex but not in the basolateral amygdala. Therefore, our results suggest that the nucleus basalis magnocellularis-cortical pathway could be in part responsible for the promnesic effect of pregnenolone sulfate. This neurosteroid acts as a negative modulator of the GABA(A) receptor complex and positively modulates the N-methyl-D-aspartate receptor, possibly resulting in a global stimulatory effect on central cholinergic neurotransmission.

Acetylcholine↗

Spatial memory in young and older adults: environmental support and contextual influences at encoding and retrieval.

Previous studies have demonstrated the existence of an "unequal facilitation" effect in spatial memory. In those experiments, the provision of appropriate environmental support for recall was shown to enhance the recall performance of older adults more than that of young adults. In some cases, this process resulted in parity of performance between the two age groups. The present study evaluated the relative contribution of environmental support to the unequal facilitation effect at encoding and retrieval in a spatial memory task. Results, indicate that, although the provision of environmental support at both encoding and retrieval is necessary for optimal recall across the adult life span, the primary influence of such support for recall in the elderly derives from its presence at encoding.

Adult↗

Effects of environmental enrichment on spatial memory and neurochemistry in middle-aged mice.

The present study compared the effects of environmental enrichment on spatial memory, glutamic acid decarboxylase (GAD) activity, and synaptophysin levels in middle-aged male and female mice. Prior to testing, a subset of 18-month-old male and female C57BL/6 mice was housed with two to three toys and a running wheel in the home cage for up to 29 d. Adult mice (7 mo) of both sexes and the remaining middle-aged mice were group (social) housed, but not exposed to enriching objects. After the enrichment period, all mice were tested in a 1-day version of the Morris water maze, in which both spatial and nonspatial memory were assessed. Immediately after testing, the hippocampus and frontoparietal cortex were dissected, and GAD activity and synaptophysin levels were measured. Environmental enrichment reduced the age-related impairment in spatial acquisition and retention; relative to adult social controls, middle-aged enriched mice were unimpaired, whereas middle-aged social controls were impaired. This reduction was similar in middle-aged males and females. Enrichment did not affect cued memory in either sex. Although hippocampal GAD activity was increased by enrichment in males, all other neurochemical measurements were unaffected by enrichment or aging in either sex. These data suggest that environmental enrichment initiated at middle age can reduce age-related impairments in spatial memory in males and females, although the underlying neurobiological mechanisms of this effect remain unknown.

Aging↗

Functional role of rat prelimbic-infralimbic cortices in spatial memory: evidence for their involvement in attention and behavioural flexibility.

The involvement of the medial prefrontal cortex (mPFC), and more particularly the prelimbic and infralimbic cortices (PL-IL area), in spatial memory remains controversial. The present study investigates the effects of neurotoxic lesions restricted to the PL-IL area of the mPFC in rats trained in two different spatial tasks. In experiment 1, PL-IL lesioned rats showed normal acquisition of a delayed non-matching to position task. They were also able to plan their responses for a prospective strategy but were transiently disrupted when the initial delay was extended. In experiment 2, rats were trained to locate one baited box among 13 identical boxes distributed on a circular arena. Lesioned rats performed normally when trained from a single start position but were severely disrupted when four start positions were used. A probe trial showed this deficit was not due to failure to learn the goal location. The addition of a proximal cue signalling the goal box helped lesioned rats to directly open the goal box, but did not compensate for greater distances that they travelled to reach it. Results from both experiments indicate that the PL-IL area is directly involved neither in allocentric spatial representations nor prospective memory and is not specifically involved in working memory. This area seems more likely to be involved in both attentional processes and behavioural flexibility that may be important for processing information for working memory as well as for spatial memory.

Animals↗

Effects of risperidone on locomotor activity and spatial memory in rats with hippocampal damage.

Hippocampal damage produces spatial memory impairment and hyperactivity in animals, while reductions in hippocampal size have been associated with memory deficits in humans. There are no known treatments for the behavioral changes specifically related to reduced hippocampal size. The purpose of this study was to determine if risperidone, an atypical antipsychotic drug that has shown cognitive-enhancing properties in animals and humans, could alleviate the behavioral disturbances produced by hippocampal damage in rats. Young adult male Sprague-Dawley rats received either sham stereotaxic surgery or direct stereotaxic infusions of N-methyl-d-aspartate (NMDA) into the dorsal hippocampus to produce hippocampal damage. One week later, animals in each group received daily subcutaneous injections of either saline or risperidone (0.2mg/kg) until the end of the experiment. Three weeks after surgery, locomotor activity was tested in all animals. During the fourth and fifth post-surgical weeks, animals were tested in a discrete-trial, delayed rewarded alternation memory paradigm. Risperidone reversed lesion-induced hyperactivity; however it also decreased activity in the sham control rats. In the delayed alternation task, there were significant drug and lesion effects irrespective of the day of testing, but there was no drugxlesion interaction. Hippocampal lesions impaired performance in the delayed alternation task in saline and risperidone-treated rats. However, risperidone modestly improved performance in lesioned and sham controls in comparison to saline-treated lesioned and sham controls. Risperidone also slowed choice time in the alternation task. These data indicate that risperidone does not specifically correct the neurobiological consequences of hippocampal damage, but that animals with hippocampal damage nonetheless maintain a significant degree of sensitivity to the beneficial effects of risperidone.

Animals↗

Spatial memory in preschool infants.

In order to test the spatial competence of preschool infants, two groups, aged 2 years and 4 years, were tested on a version of the "radial maze" task. They were required to obtain a chocolate sweet from each of eight identically labelled positions in an unfamiliar room. Four-year-olds accomplished this with considerable accuracy, rarely revisiting previously sampled positions. Two-year-olds performed marginally above chance. Variants of the task were employed, including rotation of the room configuration so that labelled positions were rendered ambiguous with respect to all other environmental stimuli. The latter caused a marked fall in performance in those infants that had been scoring above chance. By these criteria, infants clearly possess a form of intuitive "spatial memory" that is likely to mature during the second and third years. Parameters of performance were remarkably similar to those seen in comparable studies with nonhumans. It is likely that hippocampal development in early infancy underlies this evolving skill, assuming cross-species similarity in the organization of spatial behavior, and that locomotor competence is required for its development.

Age Factors↗

Orexin-saporin lesions of the medial septum impair spatial memory.

The medial septum and diagonal band of Broca (MSDB) provide a major input to the hippocampus and are important for spatial learning and memory. Although electrolytic MSDB lesions have prominent memory impairing effects, selective lesions of either cholinergic or GABAergic MSDB neurons do not or only mildly impair spatial memory. MSDB neurons are targets of orexin-containing neurons from the hypothalamus. At present, the functional significance of orexin afferents to MSDB is unclear, and the present study investigated a possible involvement of orexin innervation of the MSDB in spatial memory. Orexin-saporin, a toxin that damages neurons containing the hypocretin-2 receptor, was administered into the MSDB of rats. Rats were subsequently tested on a water maze to assess spatial reference memory and a plus maze to assess spatial working memory. At 100 ng/microl, orexin-saporin destroyed primarily GABAergic septohippocampal neurons, sparing the majority of cholinergic neurons. At 200 ng/microl, orexin-saporin almost totally eliminated GABAergic septohippocampal neurons and destroyed many cholinergic neurons. Spatial reference memory was impaired at both concentrations of orexin-saporin with a dramatic impairment observed for 24-h retention. Short-term reference memory was also impaired at both concentrations. Rats treated with 200 ng/microl, but not 100 ng/microl, of orexin-saporin were also impaired on a spontaneous alternation task, showing a deficit in spatial working memory. Our results, together with previous studies, suggest that orexin innervation of the MSDB may modulate spatial memory by acting on both GABAergic and cholinergic septohippocampal neurons.

Animals↗

Fetal transplant-induced restoration of spatial memory in rats with lesions of the nucleus basalis of Meynert.

Bilateral lesions of the nucleus basalis of Meynert (nbM) in rats produced mnemonic deficits when subjects were tested on tests of spatial memory over a period of 3 to 7.5 months postoperatively. The transplantation of cholinergic-rich, fetal ventral forebrain tissue to either two or four frontoparietal cortical sites normalized performance on the spatial memory tasks. However, which transplant condition yielded recovery depended upon the nature of the task and/or posttransplantation interval. When assessed 8 months following transplant surgery, cortical choline acetyltransferase and acetylcholinesterase activity levels in both transplant groups were comparable to those values found in sham-operated animals. These data indicate that fetal transplants can reverse the mnemonic deficits and restore cortical cholinergic neurochemical activity to near-normal levels in rats with nbM lesions.

Animals↗

Antisense knockdown of the rat alpha7 nicotinic acetylcholine receptor produces spatial memory impairment.

Selective and brain penetrating pharmacological antagonists for use in clarifying a role of alpha7 nicotinic acetylcholine receptors (nAChR) in behavioral paradigms are presently unavailable. Studies in alpha7 knock-out mice (KO) have not revealed convincing changes in behavioral phenotype, in particular measures of cognition that include contextual fear conditioning and spatial memory, which may be due to compensatory developmental changes. Therefore, an antisense oligonucleotide (aON) targeted toward the 3'- and 5'-UTR coding regions of the rat alpha7 nicotinic acetylcholine receptor was used. Following central injection of aON into the lateral ventricle of Long Evans rats for 6 days, treated rats exhibited a significant 42% and 25% decrease in alpha7 nAChR densities in hippocampus and cortex, respectively, as measured by [(3)H]-methyllycaconitine (MLA) binding. There was no change in alpha4beta2 densities measured by [(3)H]-cytisine binding. Acquisition of Morris Water Maze (MWM) performance, a measure of spatial memory, was impaired in aON-treated rats. In addition, a reduction in target platform crossings during a subsequent probe-trial was observed. These data demonstrate the ability of this aON to reduce hippocampal and cortical alpha7 nicotinic receptor densities associated with impaired MWM performance and support the specific involvement of the alpha7 nAChR in spatial learning and memory, a phenotype not affected in alpha7 KO mice.

Aconitine↗

Effects of captopril on locomotor activity, passive avoidance behaviour and spatial memory tasks in the trimethyltin-treated rat.

The potential neuroprotective/cognitive enhancing actions of captopril were investigated in the trimethyltin (TMT)-induced neurotoxicity rat model. Acute exposure to TMT produces alterations in locomotor activity, passive avoidance behaviour and spatial memory tasks. Captopril treatment given in combination with the single acute injection of TMT reversed the deficits in spatial memory tasks in 8 out of 25 trials. While post-treatment of TMT-treated rats with captopril brought about a significant improvement in 3 out of 25 trials, pre-treatment of rats for 3 weeks with captopril did not reverse the behavioural deficits produced by TMT in the Morris maze test. Captopril treatment did not block the characteristic hyperactivity or the deficits in passive avoidance behaviour of TMT-treated animals.

Animals↗