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PubMed1999

Food deprivation modulates chronic stress effects on object recognition in male rats: role of monoamines and amino acids.

An object recognition task was used to determine if chronic restraint stress (6 h/day for 21 days) impairs non-spatial memory, since chronic restraint is known to impair spatial memory. In addition, food deprivation was tested as a possible modulating factor of any stress effect in this non-reward-dependent task. Following 3 weeks of daily restraint, subjects were tested for open field activity and object recognition (over different delay intervals) during one week in two separate experiments. Experiment 1 involved testing under low demand conditions (small arena) while experiment 2 involved testing under higher-demand conditions (large arena). Basal monoamine and amino acid levels (home cage) were assessed in experiment one and monoamine arousal levels (following a sample trial) were assessed in experiment two. We observed that chronic stress impaired object recognition when the delay was extended beyond 1 h, and that food deprivation could attenuate the degree of impairment. In addition, chronic stress was associated with increased norepinephrine levels in both the amygdala and hippocampus, and dopamine (HVA/DA, DOPAC/DA) in prefrontal cortex. These changes were not observed in stress subjects that were subsequently food deprived. Food deprived subjects had higher basal serotonin activity in prefrontal cortex and hippocampus as well as higher serum CORT levels. Results suggest that food deprivation may act as a novel stress, thereby increasing subjects' arousal and attention toward the objects, which aids stressed subjects, especially in low-demand conditions. Both restraint and food deprivation affected select limbic areas associated with memory functioning.

Amino Acids↗
PubMed2004

Detrimental effects of the ketogenic diet on cognitive function in rats.

The ketogenic diet (KD) is a high-fat, low-carbohydrate, and low-protein diet that is widely used to treat epilepsy in children. Although the KD has been shown to be efficacious in the treatment of childhood epilepsy, the long-term effects of the KD on brain development are not clear. The objective of this study was to examine the long-term effects of the KD on visual-spatial memory, activity level, and emotionality in immature rats after status epilepticus (SE). Weanling rats were subjected to lithium/pilocarpine-induced SE or saline injections and were then randomized to either the KD or regular rat diet, both fed ad libitum. One month later, rats were evaluated for visual-spatial memory in the water maze, activity level in the open field test, and emotionality with the handling test. Spontaneous recurrent seizures were measured using videotaping, and seizure susceptibility was tested with flurothyl inhalation. Brains were weighed and examined for mossy fiber sprouting and cell loss. Although rats treated with the KD were active and seemed healthy, their weight gain was substantially lower than that in rats that received regular rat diet. The KD reduced the number of spontaneous seizures but had no discernible effect on flurothyl seizure susceptibility. KD-fed rats, with or without SE, had significantly impaired visual-spatial learning and memory compared with rats that were fed regular diet. The KD had minimal effects on activity level and emotionality. Rats that were treated with the KD had significantly impaired brain growth. No differences in pathology scores between the KD and regular diet groups were seen after SE. Despite reducing the number of spontaneous seizures after SE, the KD resulted in severe impairment in visual-spatial memory and decreased brain growth, with no effect on mossy fiber sprouting. This study raises concerns about the long-term effects of the KD on brain development.

Animals↗
PubMed2001

Active, passive and snapshot exploration in a virtual environment: influence on scene memory, reorientation and path memory.

We investigated the importance of active, passive and snapshot exploration on spatial memory in a virtual city. The exploration consisted in traveling along a series of streets. 'Active exploration' was performed by giving directions to the subject who controlled his displacement with a joystick. During 'passive' exploration, the travel was imposed by the computer. Finally, during 'snapshot exploration', simple views of the scene were presented sequentially every 4 m. Travel velocity was the same in all cases. The three visual exploration modes were compared with three spatial memory measures: (1) scene recognition, (2) at the end of the path, reorientation toward the departure point and (3) drawings of the path shape. Scene recognition and estimation of the direction of the starting point of the path were not affected by the mode of exploration. In contrast, reproduction of the shape of the path was affected: the errors of reproduction were greater for the snapshot exploration than for the other two conditions; there was no difference between the other two conditions. These results suggest that (1) 2D image features from a visual scene are memorized. Moreover, (2) pointing towards the origin of the path relies on motion duration integration or a frame of reference integrated during displacement. Finally, (3) drawing the path shape involves a deliberate reconstruction process.

Adult↗
PubMed1977

Distance distortions in memory for spatial locations.

The present study examined developmental differences in the effect of route extensity on the memory for the locations of objects in a spatial array. Kindergarten and adult subjects were trained to remember the locations of 4 objects. During this training, objects were either connected by a combination of indirect, looped train tracks and direct train tracks (experimental subjects) or connected by entirely direct train-track routes (control subjects). Analyses of actual interobject distances, from subjects' reproductions of object locations on a response board (without train tracks), revealed that children, but not adults, distort distance in terms of the nature of travel observed between objects. Further testing revealed that differences in the amount of time taken for travel could not account for the results obtained with children.

Adult↗
PubMedDate not supplied

Estradiol, but not raloxifene, improves aspects of spatial working memory in aged ovariectomized rhesus monkeys.

Estrogen replacement therapy (ERT) alleviates many postmenopausal symptoms but whether it also benefits cognitive function remains controversial. Further, since estrogen increases the risk of breast and uterine cancers, a new class of compounds, called selective estrogen receptor modulators (SERMs) is being considered as possible alternative to ERT. The SERM raloxifene is particularly interesting because, like estrogen, it improves lipid metabolism and reduces bone loss, without adverse effects on the breast or uterus. Little is known, however, about its effect upon cognitive function. We used a rhesus monkey model of human menopause to examine the effects of ERT and raloxifene on cognitive function. We tested 5 aged females (21-24 years old) ovariectomized long-term (10-16 years) on a battery of age-sensitive tasks, including the Delayed Response (DR), the Delayed Non-Matching-to-Sample-10 min (DNMS-10 min) and the spatial-Delayed Recognition Span Test (DRST). Monkeys were tested 5 days a week on each task for 9 consecutive months, while undergoing treatments with placebo, ethinyl estradiol (EE(2)), and raloxifene in alternating 28-days blocks. EE(2) transiently enhanced the working memory component of the spatial-DRST, but did not affect performance on the other tasks of the battery. Raloxifene had no effect on cognitive performance. These findings indicate that estradiol is able to enhance some aspects of spatial working memory in aged monkeys despite many years of estrogenic deprivation. Further, they suggest that raloxifene does not affect cognitive function after long-term ovarian hormone deprivation.

Aging↗
PubMed2005

The effects of clozapine on delayed spatial alternation deficits in rats with hippocampal damage.

Clozapine is an atypical antipsychotic drug that has been shown to improve spatial memory in some animal models; however its efficacy in reversing spatial memory impairment in rats with hippocampal lesions is unknown. To address this issue, we tested the effects of clozapine on delayed spatial alternation deficits in rats with hippocampal damage in three separate experiments. In each experiment, adult male rats received sham surgery or direct stereotaxic infusions of the excitotoxin, NMDA, into the hippocampus. In the first study, seven days after surgery, the sham control animals received daily saline injections while the lesioned animals were split into two groups that received daily saline or clozapine (2.0 mg/kg, sc) injections. During the fifth week of injections, all animals were tested in a food-motivated delayed spatial alternation task. Saline-treated rats with excitotoxic hippocampal damage displayed significant deficits in delayed spatial alternation. Daily clozapine injections completely reversed this deficit. In a second experiment, it was found that clozapine treatment limited to the testing days only did not improve alternation performance in lesioned rats. Finally, in a third experiment, chronic clozapine treatment did not improve alternation performance in lesioned rats that were pre-trained in the alternation task prior to surgery. These results suggest that chronic, but not acute, clozapine treatment enables rats with hippocampal damage to develop new spatial learning, but can not rescue old spatial learning established prior to damage. These results may have implications for the treatment of cognitive deficits caused by hippocampal dysfunction in disorders such as schizophrenia, Alzheimer's disease, and others.

Analysis of Variance↗
PubMed2001

Instability in the place field location of hippocampal place cells after lesions centered on the perirhinal cortex.

The perirhinal cortex appears to play a key role in memory, and the neighboring hippocampus is critically involved in spatial processing. The possibility exists, therefore, that perirhinal-hippocampal interactions are important for spatial memory processes. The purpose of the present study was to investigate the contribution of the perirhinal cortex to the location-specific firing ("place field") of hippocampal complex-spike ("place") cells. The firing characteristics of dorsal CA1 place cells were examined in rats with bilateral ibotenic acid lesions centered on the perirhinal cortex (n = 4) or control surgeries (n = 5) as they foraged in a rectangular environment. The activity of individual place cells was also monitored after a delay period of either 2 min, or 1 or 24 hr, during which time the animal was removed from the environment. Although the perirhinal cortex lesion did not affect the place field size or place cell firing characteristics during a recording session, it was determined that the location of the place field shifted position across the delay period in 36% (10 of 28) of the cells recorded from lesioned animals. In contrast, none of the place cells (0 of 29) recorded from control animals were unstable by this measure. These data indicate that although the initial formation of place fields in the hippocampus is not dependent on perirhinal cortex, the maintenance of this stability over time is disrupted by perirhinal lesions. This instability may represent an erroneous "re-mapping" of the environment and suggests a role for the perirhinal cortex in spatial memory processing.

Action Potentials↗
PubMed2002

Anterograde and retrograde influence of vestibular stimulation on spatial working memory.

Rats were trained in an eight-arm radial maze to explore the apparatus in search of a food reward. After completion of the training phase, some animals were submitted to a hemicerebellectomy (HCbed group), while others were used as a control group. To study the effects of vestibular stimulation on the recall of ongoing working memory information, both groups were exposed to radial maze sessions: in the first session (no-rotation), animals were confined for 30 s to the fourth arm visited without being further manipulated; in the second session (rotation), the animals were again confined for 30 s to the fourth arm visited, while the apparatus was rotated five times around its vertical axis. The effects of these manipulations on successive visits to complete the task were assessed, as well as the solving time and kinds of errors made. Errors were significantly more frequent in the control animals during the rotation session; HCbed animals were unaffected by confinement alone or by vestibular stimulation, but showed a decreased search speed. It was concluded that vestibular input is required for an adequate functioning of the working memory system devoted to the formation and consolidation of spatial mnesic traces and that the amnesic effect due to vestibular stimulation is both anterograde and retrograde in nature.

Animals↗
PubMed2001

[Neural basis of spatial orientation and memory of routes: topokinetic memory or topokinesthesic memory].

The neural basis of spatial orientation and the memory of routes have been explored by brain imaging (PET SCAN and fMRI) in human. Several cognitive strategies and several types of reference frames can be used by the brain to establish relations between our body and the environment. Four categories of brain areas have been considered: the areas involved in egocentric and allocentric coding on one hand and on the other hand the areas involved in the "route" like and the "survey or map" like strategies used during tasks in which subjects had to mentally remember a path by mental navigation or mental scanning of a map. The results have confirmed that parietal and frontal structures involved in "spatial neglect" are also found to be involved in the egocentric orientation tasks of subjective midline detection. More generally we have been able to identify parieto-frontal areas involved in visuo-spatial memory. In addition we have identified the areas involved in the cortical processing of vestibular information and lastly we have shown that in addition to the parieto-frontal areas a parieto temporal lobe network is involved in allocentric tasks and also during mental navigation by route or survey strategies. These results contribute to the identification of the neural basis of topographic memory but they also suggest that we have to define a particular type of spatial memory which is involved in the memory of routes and movements which we suggest to call "topo-kinetic" or "topo-kinesthetic" memory.

Brain Mapping↗
PubMed1998

Chronic corticosterone impairs memory performance in the Barnes maze.

Chronic stress has been reported to impair spatial memory and cause hippocampal impairment in rodents. Glucocorticoids are believed to be the active agent in this impairment. Studies have demonstrated that chronic glucocorticoid administration results in animals being impaired in the Morris water maze (MWM) or eight-arm radial maze. Although both of these methods are well established means of testing spatial memory, neither might be considered optimal for studying the behavioral effects of stress. The Morris maze is itself highly stressful to the animals. The eight-arm maze relies on a food reward to motivate the animals, and glucocorticoids have profound effects on hunger and satiety. We therefore investigated behavioral deficits of corticosterone-treated animals in the two previously used mazes and the Barnes circular platform maze (BCM), a test similar in design to the Morris maze, but one that does not require the animal to perform a highly stressful swim. Consistent with results in other tests, we found that animals that had been treated for 3 months with stress-equivalent concentrations of glucocorticoids showed significantly impaired behavior in the Barnes maze.

Animals↗
PubMed1997

Independent coding of target distance and direction in visuo-spatial working memory.

The organization of manual reaching movements suggests considerable independence in the initial programming with respect to the direction and the distance of the intended movement. It was hypothesized that short-term memory for a visually-presented location within reaching space, in the absence of other allocentric reference points, might also be represented in a motoric code, showing similar independence in the encoding of direction and distance. This hypothesis was tested in two experiments, using adult human subjects who were required to remember the location of a briefly presented luminous spot. Stimuli were presented in the dark, thus providing purely egocentric spatial information. After the specified delay, subjects were instructed to point to the remembered location. In Exp. 1, temporal decay of location memory was studied, over a range of 4-30 s. The results showed that (a) memory for both the direction and the distance of the visual target location declined over time, at about the same rate for both parameters; however, (b) errors of distance were much greater in the left than in the right hemispace, whereas direction errors showed no such effect; (c) the distance and direction errors were essentially uncorrelated, at all delays. These findings suggest independent representation of these two parameters in working memory. In Exp. 2 the subjects were required to remember the locations of two visual stimuli presented sequentially, one after the other. Only after both stimuli had been presented did the subject receive a signal from the experimenter as to which one was to be pointed to. The results showed that the encoding of a second location selectively interfered with memory for the direction but not for the distance of the to-be-remembered target location. As in Exp. 1, direction and distance errors were again uncorrelated. The results of both experiments indicate that memory for egocentrically-specified visual locations can encode the direction and distance of the target independently. Use of motor-related representation in spatial working memory is thus strongly suggested. The findings are discussed in the context of multiple representations of space in visuo-spatial short-term memory.

Adult↗
PubMed2001

Removing zinc from synaptic vesicles does not impair spatial learning, memory, or sensorimotor functions in the mouse.

Zinc-enriched (ZEN) neurons are distributed widely throughout the brain and spinal cord. Synaptic vesicle zinc in these neurons is thought to function as a neuromodulator upon its release into the synaptic cleft. Consistent with this possibility, zinc or zinc chelators can alter spatial learning, working memory, and nociception in rodents. Here we use zinc transporter-3 (ZnT3) knockout mice, which are depleted of synaptic vesicle zinc, to assess the consequences of removing this potential neuromodulator on the behavior of adult mice. ZnT3 knockout mice performed equally as well as wild-type mice in the rotarod, pole, and cagetop tests of motor coordination. They exhibited normal thermal nociception in the hot-plate and tail-flick tests, and had similar olfactory, auditory and sensorimotor gating capabilities as wild-type mice. ZnT3 knockout mice behaved similarly as wild-type mice in the open field test and in the elevated plus maze test of anxiety. They exhibited normal learning and memory in the passive avoidance, Morris water maze, and fear conditioning tasks, and normal working and reference memory in a water version of the radial arm maze. We conclude that synaptic vesicle zinc is not essential for mice to be able to perform these tasks, despite the abundance of ZEN neurons in the relevant regions of the CNS. Either the neuromodulatory effects of zinc are not relevant for the tasks tested here, or mice are able to compensate easily for the absence of synaptic vesicle zinc.

Animals↗
PubMed2004

The long-term stability of new hippocampal place fields requires new protein synthesis.

The hippocampus is critical for formation of spatial memories. Hippocampal pyramidal neurons in freely behaving animals exhibit spatially selective firing patterns, which taken together form an internal representation of the environment. This representation is thought to contribute to the hippocampal spatial memory system. Behavioral long-term memories differ from short-term memories in requiring the synthesis of new proteins. Does the development of the internal hippocampal representation also require the synthesis of new proteins? We found that blocking protein synthesis in the brain of mice by 95% does not affect short-term stability of newly formed hippocampal place fields but abolishes stability in the long term. By contrast, inhibiting protein synthesis does not affect the retention and recall of previously established fields in a familiar environment, indicating that protein synthesis-dependent reconsolidation is not required for recall. Our results indicate that place fields parallel both behavioral memories and the late phase of long-term potentiation in requiring the synthesis of new proteins for consolidation.

Action Potentials↗
PubMed2002

Sex differences in chronic stress effects on memory in rats.

Recent studies in rodent models and in humans have shown that the status of both the gonadal and adrenal axes (hypothalamic-pituitary-gonadal, HPG and hypothalamic-pituitary-adrenal, HPA, respectively) can influence learning and memory function. In this article, the effects of activating the HPA axis (stress) on performance of memory tasks in rats are reviewed. More importantly, results are presented which show that chronic stress has a different impact on performance of these tasks depending upon the sex of the rat. These observations are novel and potentially important since few studies, animal or human, have utilized females as subjects in studies of the stress response. Sex differences in the effects of chronic stress on memory were investigated in rats using an object recognition task and two spatial memory tasks, radial arm maze and object location. Given the same chronic stress--21 days of restraint for 6 h each day--males were impaired in all of the memory tests while females showed enhanced performance of the spatial memory tasks and no changes in object recognition performance. Levels of neurotransmitters and metabolites were measured in brain areas important for cognition in the subjects in order to determine neural systems that may respond to stress and mediate the cognitive responses. These results show that responses of monoamine and amino acid containing neural systems may contribute to or underlie sex differences in stress effects on cognition. Stress decreased dopaminergic activity in the frontal cortex and amygdala of males but not females; whereas, in CA3 of the hippocampus, stress increased levels of 5-HT and norepinephrine in females, but not males, and increased GABA in males, but not females. Finally, a possible role for estradiol in mediating sexually differentiated responses to stress was examined. Behavioral and neurochemical evaluations in ovariectomized, stressed females, with or without estrogen replacement, suggest that sex differences in response to stress are influenced by both the organizing and activating effects of estradiol. A few, recent studies in humans, that show sexually dimorphic relationships between chronic stress and cognition, are also highlighted. These results in humans are consistent with the pattern of results in rats. Clearly, further studies are necessary to substantiate sex differences in stress effects on memory function in humans and to understand mechanisms whereby estrogen may influence the stress response in rats. Nonetheless, recent studies show sexually differentiated cognitive responses to chronic stress and underline the importance of considering the sex/gender of subjects when studying the stress response.

Animals↗
PubMed2006

Cognitive functions in children with benign childhood epilepsy with centrotemporal spikes (BECTS).

Benign childhood epilepsy with centrotemporal spikes (BECTS) is regarded as a benign form of epilepsy because of its usually favorable outcome, in terms of seizures. Eighteen children with BECTS were studied in terms of neuropsychological and learning abilities: intellectual quotient, oral language (phonological production, naming skills, verbal fluency and syntactic comprehension), drawing and visuo-spatial skills, visual and selective attention, verbal and visuo-spatial memory, reading, numeracy and spelling. The mean IQ of the population was within the normal range, but individual results were heterogeneous. Verbal functions and memory were normal. In contrast, drawing and visuo-spatial skills, attention and visuo-spatial memory were significantly weak compared to the normal range for age. Reading, numeracy and/or spelling ability were significantly delayed by one academic year or more in ten of the children. In conclusion, despite its benign outcome in terms of epilepsy, BECTS can be accompanied by specific cognitive disorders and low academic achievement.

Anticonvulsants↗
PubMed2003

Dissociation of egocentric and allocentric spatial processing in prefrontal cortex.

Monkeys with lesions of areas 9 and 46 performed three variants of the spatial delayed response (SDR) task. There were no impairments in allocentric spatial memory in which geometrical relationships between environmental cues were used to identify spatial location; thus, memory of a 3D environmental map is intact. In contrast, there were severe impairments in egocentric spatial memory guided by visual or tactile cues that monkeys can relate to their viewing perspective during testing. These results strongly suggest that dorsolateral prefrontal cortex selectively mediates spatial memory tasks that are solved by referencing the location of targets to the body's orientation.

Animals↗
PubMed1993

Covariations between hippocampal mossy fibres and working and reference memory in spatial and non-spatial radial maze tasks in mice.

Male mice from nine inbred mouse strains were tested at the age of 3 months in either a spatial or a non-spatial version of the radial maze. Only four out of eight arms contained food rewards, permitting simultaneous assessment of working and reference memory in both situations. Other animals from the same strains were processed histologically to estimate the strain-specific extents of the mossy fibre projections. No significant between-task correlations were obtained for either working or reference memory. However, measures of working and reference memory correlated with each other within tasks. This suggests that these concepts may perhaps not be validly used in the mouse. Large, positive correlations of the size of the intra- and infrapyramidal mossy fibre projection with both working and reference memory were obtained in the spatial radial maze task, but not in the non-spatial one. We conclude that heritable variations of the hippocampal intra- and infrapyramidal mossy fibre projection influence processes related to spatial learning capabilities in radial mazes.

Animals↗