Spatial memory in rats: time course of working memory and effect of anesthetics.
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Anesthetics↗
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Failure of mice to demonstrate spatial memory in the radial maze.
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Animals↗
Spatial memory and visual evoked potentials in young and old rats after housing in an enriched environment.
The effects of aging and of housing in an enriched environment on performance in an 8-arm radial maze were evaluated in young adult (7-8 months) and old (30-33 months) male Brown-Norway rats, using a procedure in which the rats were confined for 8 s to the central platform of the maze between consecutive choices. Although the old rats attained a level of performance which was clearly above change, they were shown to perform worse than the young rats. No performance differences were found between differentially housed rats of the same age group. In a second experiment recovery cycles of visual evoked potentials were determined in the same rats by using paired flashes with an interstimulus time of 400, 300, 200, or 100 ms. Recovery was consistently smaller in the old rats as compared to the young ones. No correlation could be demonstrated, however, between radial maze performance or housing condition and recovery functions of the visual evoked potentials. This finding indicates that a decline in visual sensitivity cannot readily explain the impaired radial maze performance of old rats. Evidence which suggests that age-related hippocampal changes play a major role in the radial maze performance deficit is discussed.
Age Factors↗
Effects of intraventricular infusion of the N-methyl-D-aspartate (NMDA) receptor antagonist AP5 on spatial memory of rats in a radial arm maze.
Rats were trained to asymptotic performance in an 8-arm radial maze. They then received chronic intraventricular infusion of either artificial CSF or the N-methyl-D-aspartate (NMDA) receptor antagonist D-2-amino-5- phosphonopentanoic acid (AP5), at a concentration (30 mM) that has been shown previously to prevent the induction of long-term potentiation in the dentate gyrus of the hippocampus in vivo. Subsequently the rats received another 9 trials in the maze in a quasi-random order, 3 uninterrupted trials, and another 6 trials each with mid-trial delays of 5, 20 or 60 min during which the animals were placed in their home cage. The mean number of errors for the AP5 rats did not differ significantly from that of the controls in the uninterrupted trials throughout the experiment, nor did it differ from that of the controls in any of the 3 delayed trials when these were first introduced. However, the control animals performed better at the longer delays when these were introduced for the second time, whilst there was no such improvement (but rather a deterioration) for the AP5 animals. The impairment of performance in the AP5 rats during the second block of delayed trials was significant, and independent of the length of the delay. These results show that NMDA receptor blockade does not impair working memory in the radial maze per se, but that it does prevent an improvement of working memory persistence with further training.
2-Amino-5-phosphonovalerate↗
Dissociation of impairment between spatial memory, and motor function and emotional behavior in aged rats.
We investigated changes in learning and memory in aged rats, in relation to motor function and emotional behavior. Male Kbl Wistar aged rats (108-weeks-old) were divided into two groups, memory impaired and non-impaired, based on performance during six training trials in the Morris water maze task. Aged rats with a goal latency longer than the mean plus the 99% confidence limit of young rats, were regarded as memory impaired, whereas those with a goal latency within the range of the 99% confidence limit of the mean of young rats, were considered as memory non-impaired. Although the performance of the memory impaired aged rats in the standard test of the Morris water maze improved after six re-training trials to the level of the non-impaired aged rats and young rats, working memory impairment was evident. There were no differences in motor function and emotional behavior between the impaired and non-impaired aged rats. These results suggest that deficits of learning and memory in memory impaired aged rats can be dissociated from changes in motor function and emotional behavior.
Aging↗
Slow brain potentials in a visual-spatial memory task: topographic distribution and inter-laboratory consistency.
Slow brain electrical potentials (SPs) were investigated in a visual-spatialmemory task. Two issues were addressed: (1) the nature and topographic distribution of the potentials obtained under such conditions; and (2) the consistency of the SPs when recorded in six identically configured laboratories. Fifteen young male subjects were studied at each laboratory (total n = 90). The paradigm entailed presentations of paired-visual patterns (S1 and S2), to which subjects responded with a choice reaction time response indicating whether or not the two patterns matched. A biphasic contingent negative variation (CNV) was produced which consisted of an early symmetric component with bilateral foci at posterior temporal sites and a subsequent mid-parietal dominant wave later in the retention interval. Although the CNVs from all laboratories were similar in waveform and in topographic distribution, there were significant inter-laboratory differences in amplitude of the slow potential components. The topographic distributions of the components and the possible role of sampling effects are discussed.
Adult↗
Decline in visual attention and spatial memory in aged rats.
The present study was a longitudinal study of age-related changes in performance of the 5-choice serial reaction time task, a test of visual attention. Following acquisition of the task, animals were tested on two occasions on their ability to perform the 5-choice task. In Test 1 (Young: 7 months; Aged: 13-14 months) no age-related effects on baseline performance were revealed. However, increasing the attentional load of the task revealed an impairment in choice accuracy by animals of the Aged group. In Test 2 (Young: 10-11 months; Aged 23-24 months), animals of the Aged group were significantly impaired on the baseline schedule of the task compared to the Young group. The deficit in accuracy on the task could be improved in the Aged animals by decreasing the attentional load. The results of the present study suggest a deficit in attentional function as a result of the aging process, markedly similar to that observed following lesions of the basalo-cortical cholinergic system.
Aging↗
Spatial memory testing decreases hippocampal amyloid precursor protein in young, but not aged, female rats.
Using young and aged rats, we investigated relationships between amyloid precursor protein (APP) and working or reference memory, as well as assessed whether cognitive testing altered APP levels. In young rats, higher APP levels were related to more working memory errors as a linear function. Aged rats exhibited a curvilinear relationship between APP and working memory, with moderate APP levels associated with better relative performance. A comparison of rats that received cognitive testing with those that did not showed that testing decreased APP levels in young, but not aged, rats. Collectively, the data suggest that young and aged rats exhibit different relationships between APP and working memory, and that aged rats do not maintain the capacity to decrease APP in response to cognitive testing.
Aging↗
Effects of chronic restraint stress and estradiol on open field activity, spatial memory, and monoaminergic neurotransmitters in ovariectomized rats.
Twenty-one days of chronic restraint stress impairs male rat performance on the radial arm maze [Luine et al. (1994) Brain Res. 639, 167-170], but enhances female rat performance [Bowman et al. (2001) Brain Res. 904, 279-289]. To assess possible ovarian hormone mechanisms underlying this sexually dimorphic response to stress, we examined chronic stress effects in ovariectomized rats. Ovariectomized rats received Silastic capsule implants containing cholesterol or estradiol and were assigned to a daily restraint stress (21 days, 6 h/day) or non-stress group. Following the stress period, subjects were tested for open field activity and radial arm maze performance. Stress and estradiol treatment affected open field activity. All stressed animals, with or without estradiol treatment, made fewer total outer sector crossings. In contrast, estradiol-treated animals, with or without stress, made more inner sector visits, an indication that estradiol decreased anxious behavior on the open field across time. As measured by the total number of visits required to complete the task, stress did not affect radial arm maze performance in ovariectomized rats, but estradiol-treated animals, with or without stress, performed better than non-treated animals on the radial arm maze. Stressed subjects receiving estradiol showed the best radial arm maze performance. Following killing, tissue samples were obtained from various brain regions known to contribute to learning and memory, and monoamine and metabolite levels were measured. Several changes were observed in response to both stress and estradiol. Most noteworthy, stress treatment decreased homovanillic acid levels in the prefrontal cortex, an effect not previously observed in stressed intact females. Estradiol treatment increased norepinephrine levels in CA3 region of the hippocampus, mitigating stress-dependent changes. Both stress and estradiol decreased dentate gyrus levels of 5-hydroxyindole acetic acid. In summary, the current study provides novel information showing that estradiol alters behavioral and neurochemical responses to stress in ovariectomized rats. Estradiol treatment decreased anxious behavior on the open field and stressed animals receiving estradiol had enhanced radial arm maze performance. In relation to interactions between stress and estradiol on cognition and anxiety, changes in the prefrontal cortex dopaminergic system, dentate gyrus serotonergic system, and norepinephrine levels in the CA3 region appear important. Results show that estradiol may moderate stress effects on cognition and anxiety through both organizational and activation effects.
Animals↗
Reversible inhibition of CREB/ATF transcription factors in region CA1 of the dorsal hippocampus disrupts hippocampus-dependent spatial memory.
CREB is critical for long-lasting synaptic and behavioral plasticity in invertebrates. Its role in the mammalian hippocampus is less clear. We have interfered with CREB family transcription factors in region CA1 of the dorsal hippocampus. This impairs learning in the Morris water maze, which specifically requires the dorsal hippocampus, but not context conditioning, which does not. The deficit is specific to long-term memory, as shown in an object recognition task. Several forms of late-phase LTP are normal, but forskolin-induced and dopamine-regulated potentiation are disrupted. These experiments represent the first targeting of the dorsal hippocampus in genetically modified mice and confirm a role for CREB in hippocampus-dependent learning. Nevertheless, they suggest that some experimental forms of plasticity bypass the requirement for CREB.
Activating Transcription Factor 1↗
Effect of the postictal state on visual-spatial memory in immature rats.
Postictal cognitive impairment following seizures can last from minutes to days and be disabling to the patient. The purpose of this study was to compare the behavioral features of seizures with postictal memory impairment in young seizure-naive rats and rats with a prior history of status epilepticus (SE) and examine the relationship between postictal EEG changes and cognitive recovery. Following training in the water maze to asymptote levels of learning, rats with a prior history of SE and seizure-naive rats had flurothyl-induced generalized seizures and time to recovery to baseline was then measured. Following generalized seizures rats had impaired performance in the water maze with the duration of the cognitive deficits exceeding the length of the seizure. There was not a close relationship between duration of cognitive impairment and either latency to onset of seizure or duration. The animal's neurological status was a factor in the duration of cognitive impairment following seizures; while there were no differences between SE and seizure-naive rats in latency to seizure onset or duration of the seizures, animals with a prior history of SE had a longer period of impairment following a seizure than animals without such a history. Postictal cognitive impairment was associated with changes in theta activity in animals with a prior history of SEs but not in seizure-naive animals. Caffeine, when administered following the seizure, reduced postictal cognitive impairment in a dose-dependent manner. This study demonstrates that duration of postictal cognitive impairment is not directly related to duration of the seizure. The neurological status of the animal is a determining factor in duration of postictal impairment.
Animals↗
Applications of virtual reality technology in the measurement of spatial memory in patients with mood disorders.
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Humans↗
Spatial memory of heterozygous staggerer (Rora(+)/Rora(sg)) versus normal (Rora(+)/Rora(+)) mice during aging.
Heterozygous staggerer mice (Rora(+)/Rora(sg)) and control mice (Rora(+)/Rora(+)) of the same C57BL/6J strain background were tested in a spontaneous alternation task at 3 to 24 months old. The results demonstrated a decrement in long-term working memory as early as 6 months in Rora(+)/Rora(+) mice and at 3 months in Rora(+)/Rora(sg) mice. Previous studies showed that in both cases, neuronal number in the cerebellar cortex was normal. This suggests that age-dependent decrease in long-term working memory would be due to fine structural or biochemical changes preceding neuronal death in the cerebellum. Such subtle changes would occur more precociously in Rora(+)/Rora(sg) than in Rora(+)/Rora(+) mice. Also, short-term working memory was preserved in Rora(+)/Rora(+) mice as old as 24 months, but was impaired in 6-month-old Rora(+)/Rora(sg) mice.
Aging↗
The role of self-to-object updating in orientation-free performance on spatial-memory tasks.
A single view of a room-sized path produces an orientation-specific memory representation, yet when memory is tested at a location on the path, orientation-free performance is observed. Either a virtual-views or an updating hypothesis can account for orientation-free performance by attributing it, respectively, to an orientation-free long-term-memory representation or to a working-memory representation of the body's updated location relative to the path. Experiments 1 and 2 test these hypotheses by manipulating the test-site location and the complexity of the trajectory from the study site to the test site. Experiment 3 tests orientation to the test space as a function of trajectory complexity. Results support a virtual-views explanation for the orientation-free performance of males and an updating explanation for females.
Adolescent↗
Parallel modifications of spatial memory performances, exploration patterns, and hippocampal theta rhythms in fornix-damaged rats: reversal by oxotremorine.
Learning scores and degrees of divergence of the exploratory patterns (EP) displayed during the acquisition stage of a radial eight-arm maze task were examined in fornix-damaged and sham-operated rats injected either with oxotremorine (0.1 mg/kg) or saline. Modifications of hippocampal rhythmic slow activity (theta) recorded in each condition were analyzed in CA1 and dentate gyrus. Dorsal fornix sections reduced choice accuracy but also induced the adoption of weakly divergent EP. Oxotremorine in animals with lesions reinstates both learning scores and degree of divergence of EP at the levels respectively observed in saline sham-operated animals. Finally, oxotremorine in sham-operated animals did not significantly improve choice accuracy but strongly modified the EP. Preoperatively, theta rhythms indicated a decrease of frequency after oxotremorine administration. Postoperatively, they showed an increase of frequency in animals with lesions that were reinstated at the preoperative level by oxotremorine.
Animals↗
Effects of lesions of the associative parietal cortex on the acquisition and use of spatial memory in egocentric and allocentric navigation tasks in the rat.
It has been hypothesized that the rat associative parietal cortex (APC) is involved in the association between visuospatial and locomotion-generated (kinesthetic) information. To study the kinesthetic component, APC-lesioned and control rats were trained in total darkness to reach a submerged platform in the Morris water maze. In the egocentric task, the relative position of the starting point and the platform was constant all over training. Parietal rats have been found impaired in acquisition and to a less extent in retention of this task. In the allocentric task, rats were then trained in the standard version of the navigation task. A mild deficit was observed in acquisition of this task because the APC-lesioned rats displayed longer escape latencies but control-like search patterns. These results suggest that the APC is involved in the coding of kinesthetic information that plays an important role in place navigation.
Animals↗
Role of noradrenergic function in the opiate antagonist facilitation of spatial memory.
Animals previously trained to criterion on an eight-arm radial maze task received either bilateral 6-hydroxydopamine lesions of the dorsal noradrenergic bundle (DNB) or control surgery. Following a 3-week recovery period, the animals were trained on the same radial maze in two novel environments. By a within-subjects design, in one of these environments animals received posttraining systemic treatment with the opiate antagonist naloxone; in the other novel environment, they received vehicle injection. In animals that received control surgery, opiate antagonist treatment produced a reliable enhancement of performance. Although the DNB-lesion animals did not differ from the control-surgery animals under the saline treatment condition, denervation of forebrain norepinephrine (NE) was found to prevent the memory enhancing effect of posttraining naloxone administration. These results provide further support that enhanced retention obtained with opiate antagonist administration is dependent upon intact NE function.
Animals↗
The hippocampal role in spatial memory and the familiarity--recollection distinction: a case study.
Memory for object locations and for events (comprising the receipt of an object) was tested in a case of developmental amnesia with focal hippocampal damage. Tests used virtual reality environments and forced-choice recognition with foils chosen to equalize the performance of control participants across conditions. Memory for the objects received was unimpaired, but the context of their receipt was forgotten. Memory for short lists of object locations was unimpaired when tested from the same viewpoint as presentation but impaired when tested from a shifted viewpoint. Same-view performance was disrupted by changing the background scene. These results are consistent with Jon having preserved matching to fixed sensory-bound representations but impaired reconstructed or manipulable representations underlying shifted-viewpoint recognition and episodic recollection.
Adult↗