Daytime Sleep Enhances Consolidation of the Spatial but Not Motoric Representation of Motor Sequence Memory

Motor sequence learning is known to rely on more than a single process. As the skill develops with practice, two different representations of the sequence are formed: a goal representation built under spatial allocentric coordinates and a movement representation mediated through egocentric motor coordinates. This study aimed to explore the influence of daytime sleep (nap) on consolidation of these two representations. Through the manipulation of an explicit finger sequence learning task and a transfer protocol, we show that both allocentric (spatial) and egocentric (motor) representations of the sequence can be isolated after initial training. Our results also demonstrate that nap favors the emergence of offline gains in performance for the allocentric, but not the egocentric representation, even after accounting for fatigue effects. Furthermore, sleep-dependent gains in performance observed for the allocentric representation are correlated with spindle density during non-rapid eye movement (NREM) sleep of the post-training nap. In contrast, performance on the egocentric representation is only maintained, but not improved, regardless of the sleep/wake condition. These results suggest that motor sequence memory acquisition and consolidation involve distinct mechanisms that rely on sleep (and specifically, spindle) or simple passage of time, depending respectively on whether the sequence is performed under allocentric or egocentric coordinates.     

Estradiol enhances DMP acquisition via a mechanism not mediated by turning strategy but which requires intact basal forebrain cholinergic projections

This study examined whether effects on turning strategy, use of an allocentric strategy, and/or short-term spatial memory account for the effects of estradiol treatment on acquisition of a delayed matching-to-position (DMP) T-maze task, in rats with and without basal forebrain cholinergic lesions. Ovariectomized rats received either 192IgG saporin (SAP) or saline injected into the medial septum. Two weeks later, half of each group received either continuous estradiol treatment (5-mm silastic capsule containing 17-beta-estradiol implanted s.c.) or implantation of an empty capsule. All rats were trained on the DMP task. Results show that estradiol enhanced, and SAP lesions impaired, learning on the DMP task. SAP lesions impaired learning primarily by increasing the use of a persistent turning strategy early on during training. In contrast, estradiol had no apparent effect on turning strategy, and enhanced learning only in non-lesioned rats. There was no evidence that any of these effects were due primarily to an effect on ultimate strategy selection (e.g., allocentric vs. egocentric, evaluated with a probe trial in which the maze was rotated 180 degrees), or on short-term spatial memory (evaluated by increasing the intertrial delay). We conclude that estradiol enhances DMP acquisition via a mechanism independent of effects on turning strategy and short-term memory, but nevertheless dependent on cholinergic neurons in the MS and VDB. We hypothesize that estradiol may affect the facility with which female rats are able to extract and incorporate extramaze information into an effective navigational strategy, and that this may be mediated by effects in prefrontal cortex.     

Spatial memory and orientation strategies in the elasmobranch<Emphasis Type="Italic"> Potamotrygon motoro</Emphasis>

We investigated whether juvenile freshwater stingrays (Potamotrygon motoro) can solve spatial tasks by constructing a cognitive map of their environment. Two experimental conditions were run: allocentric and ego-allocentric. Rays were trained to locate food within a four-arm maze placed in a room with visual spatial cues. The feeding location (goal) within the maze (room) remained constant while the starting position varied for the allocentrically but not for the ego-allocentrically trained group. After training, all rays solved the experimental tasks; however, different orientation strategies were used within and between groups. Allocentrically trained rays reached the goal via novel routes starting from unfamiliar locations, while ego-allocentrically trained rays primarily solved the task on the basis of an egocentric turn response. Our data suggest that P. motoro orients by constructing a visual cognitive map of its environment, but also uses egocentric and/or other orientation strategies alone or in combination for spatial orientation, a choice which may be governed by the complexity of the problem. We conclude that spatial memory functions are a general feature of the vertebrate brain.     

Hippocampus, ageing, and taste memories

Previous studies have shown that ageing may induce deficits in hippocampal-dependent learning and memory tasks, the spatial task being most extensively applied in rats. It is proposed that taste learning and memory tasks may assist in understanding the ageing of memory systems, giving access to a more complete picture. Taste learning tasks allow us to explore a variety of learning phenomena in safe and aversive memories using similar behavioral procedures. In demanding the same sensory, response, and motivational requirements, this approach provides reliable comparisons between the performance of hippocampal lesioned and aged rats in different types of memory. Present knowledge on the effect of both ageing and hippocampal damage in complex taste learning phenomena is reviewed. Besides inducing deficits in hippocampal-dependent phenomena, such as blocking of conditioned taste aversion, while at the same time leaving intact nonhippocampal-dependent effects, such as latent inhibition, ageing is also associated with an increased neophobia by previous aversive taste memories and enhanced taste aversion conditioning which cannot be explained by age-related changes in taste or visceral distress sensitivity. In all, the results indicate a peculiar organization of the memory systems during aging that cannot be explained by a general cognitive decline or exclusively by the decay of the hippocampal function.     

My Hand or Yours? Markedly Different Sensitivity to Egocentric and Allocentric Views in the Hand Laterality Task

In the hand laterality task participants judge the handedness of visually presented stimuli--images of hands shown in a variety of postures and views--and indicate whether they perceive a right or left hand. The task engages kinaesthetic and sensorimotor processes and is considered a standard example of motor imagery. However, in this study we find that while motor imagery holds across egocentric views of the stimuli (where the hands are likely to be one's own), it does not appear to hold across allocentric views (where the hands are likely to be another person's). First, we find that psychophysical sensitivity, d', is clearly demarcated between egocentric and allocentric views, being high for the former and low for the latter. Secondly, using mixed effects methods to analyse the chronometric data, we find high positive correlation between response times across egocentric views, suggesting a common use of motor imagery across these views. Correlations are, however, considerably lower between egocentric and allocentric views, suggesting a switch from motor imagery across these perspectives. We relate these findings to research showing that the extrastriate body area discriminates egocentric ('self') and allocentric ('other') views of the human body and of body parts, including hands.     

Long-term retention and overshadowing of proximal and distal cues following habituation in an object exploration task

The object displacement task is a popular tool used to investigate spatial learning and memory. However, little attention has previously been given to long-term retention of spatial information following habituation to this task. Furthermore, the role of both proximal and distal cues in this type of passive retention of spatial information is controversial. In Study 1, we examined habituation in the object displacement task across 4 days and examined reactivity to spatial change 7 days post-acquisition. We found that rats habituated rapidly to the environment and retained this environment for the 7 days. Furthermore, this experiment shows that both proximal and distal spatial cues are important in the encoding of the environment during object displacement learning task. In Study 2, we examined the effect of overshadowing and demonstrate that proximal visual spatial cues can overshadow distal spatial cues if a conflict arises between both set.     

Preventive action of Ginkgo biloba in stress- and corticosterone-induced impairment of spatial memory in rats

In this study, we tested preventive effects of a natural medicine the extract of Ginkgo biloba (EGB 761) on post-stress cognitive dysfunction. Exposure to chronic restraint stress in rats and psychosocial stress in humans has been shown to alter cognitive functions such as learning and memory and have been linked to the pathophysiology of mood and anxiety disorders.Our findings indicate that chronic restraint stress impaired egocentric spatial memory as observed in the eight-arm radial maze but it did not alter the allocentric spatial memory in the Morris water maze. In control rats EGB 761 (100 mg/kg, orally) improved spatial memory in these two tests. Also, EGB 761 normalized cognitive deficits seen in rats chronically stressed or treated with an ‘equivalent’ dose of exogenous corticosterone (5 mg/kg, subcutaneously).We conclude that, in rats, repeated administration of EGB 761 prevents stress- and corticosterone-induced impairments of spatial memory.     

Egocentric Representation Acquired from Offline Map Learning

It is widely accepted that people establish allocentric spatial representation after learning a map. However, it is unknown whether people can directly acquire egocentric representation after map learning. In two experiments, the participants learned a distal environment through a map and then performed the egocentric pointing tasks in that environment under three conditions: with the heading aligned with the learning perspective (baseline), after 240° rotation from the baseline (updating), and after disorientation (disorientation). Disorientation disrupted the internal consistency of pointing among objects when the participants learned the sequentially displayed map, on which only one object name was displayed at a time while the location of “self” remained on the screen all the time. However, disorientation did not affect the internal consistency of pointing among objects when the participants learned the simultaneously displayed map. These results suggest that the egocentric representation can be acquired from a sequentially presented map.     

Cues used by male and female hooded rats for locating a brightness change

Entries of and time spent in a novel Y-maze arm that had changed from white (during acquisition trials) to black (during retention trials) were investigated in male and female Long-Evans hooded rats after the apparatus had been horizontally rotated through 180 degrees or left undisturbed. Maze rotation reduced responsiveness to this arm in males but not in females. When each arm was associated with a different set of visual cues, males significantly chose the novel arm only in the presence of intra- and extra-maze cues either alone or in combination. Females significantly selected the novel arm only in the absence of either type of cue, and in the presence of intra-maze cues alone. However, when the duration of acquisition trials was increased from 6 to 12min, females also selected the novel arm in the presence of both intra- and extra-maze cues. It was concluded that, while female rats appeared able to use egocentric (or response-related) cues for locating the novel arm, males were more dependent on allocentric (or place-related) cues following shorter acquisition trials. Because of the importance of such cues, it seemed that the task of recognizing which maze arm had changed in brightness defined the test as one of spatial memory.     

Shifts in preferred learning strategy across the estrous cycle in female rats

The current status of the effects of ovarian steroids on learning and memory remains somewhat unclear, despite a large undertaking to evaluate these effects. What is emerging from this literature is that estrogen, and perhaps progesterone, influences learning and memory, but does so in a task-dependent manner. Previously, we have shown that ovariectomized rats given acute treatments of estrogen acquire allocentric or "place" tasks more easily than do rats deprived of estrogen, but acquire egocentric or "response" learning tasks more slowly than do those deprived of hormone, suggesting that estrogen treatment may bias the strategy a rat is able to use to solve tasks. To determine if natural fluctuations in ovarian hormones influence cognitive strategy, we tested whether strategy use fluctuated across the estrous cycle in reproductively intact female rats. We found that in two tasks in which rats freely choose the strategy used to solve the task, rats were more likely to use place strategies at proestrous, that is, when ovarian steroids are high. Conversely, estrous rats were biased toward response strategies. The data suggest that natural fluctuations in ovarian steroids may bias the neural system used and thus the cognitive strategies chosen during learning and memory.     

Impact of estrogen receptor alpha and beta agonists on delayed alternation in middle-aged rats

Estrogens act in the adult brain to modulate cognition, enhancing performance on some learning tests and impairing performance on others. Our previous research has revealed an impairing effect of chronic 17β-estradiol treatment in young and aged rats on a prefrontally-mediated working memory task, delayed spatial alternation (DSA). Little is known about the mechanisms of these impairing effects. The current study examined the effects of selective estrogen receptor (ER) α or ERβ activation on DSA performance in middle-aged female rats. Ovariectomized 12 month old Long–Evans (LE) rats were treated by subcutaneous injection with the ERα agonist propyl pyrazole triol (PPT) or the ERβ agonist diarylpropionitrile (DPN) at 0.02, 0.08, or 0.20 mg/kg/day, or with oil vehicle and tested on an operant variable delay DSA task. A 17β-estradiol group (10% in cholesterol) was included as a positive control group. We replicated our previous finding of a 17β-estradiol induced deficit on DSA performance and this effect was paralleled by low dose (0.02 mg/kg/day) DPN treatment. Higher doses of DPN failed to produce a significant change in performance. The highest dose of PPT (0.20 mg/kg/day) also impaired performance, but this effect was subtle and limited to the longest delay during the final block of testing. These data confirm our earlier findings that chronic 17β-estradiol treatment has an impairing effect on the DSA task, and suggest that ERβ activation may underlie the deficit.     

Impact of estrogen receptor alpha and beta agonists on delayed alternation in middle-aged rats

Estrogens act in the adult brain to modulate cognition, enhancing performance on some learning tests and impairing performance on others. Our previous research has revealed an impairing effect of chronic 17β-estradiol treatment in young and aged rats on a prefrontally-mediated working memory task, delayed spatial alternation (DSA). Little is known about the mechanisms of these impairing effects. The current study examined the effects of selective estrogen receptor (ER) α or ERβ activation on DSA performance in middle-aged female rats. Ovariectomized 12 month old Long–Evans (LE) rats were treated by subcutaneous injection with the ERα agonist propyl pyrazole triol (PPT) or the ERβ agonist diarylpropionitrile (DPN) at 0.02, 0.08, or 0.20 mg/kg/day, or with oil vehicle and tested on an operant variable delay DSA task. A 17β-estradiol group (10% in cholesterol) was included as a positive control group. We replicated our previous finding of a 17β-estradiol induced deficit on DSA performance and this effect was paralleled by low dose (0.02 mg/kg/day) DPN treatment. Higher doses of DPN failed to produce a significant change in performance. The highest dose of PPT (0.20 mg/kg/day) also impaired performance, but this effect was subtle and limited to the longest delay during the final block of testing. These data confirm our earlier findings that chronic 17β-estradiol treatment has an impairing effect on the DSA task, and suggest that ERβ activation may underlie the deficit.     

Impaired representation of geometric relationships in humans with damage to the hippocampal formation

The pivotal role of the hippocampus for spatial memory is well-established. However, while neurophysiological and imaging studies suggest a specialization of the hippocampus for viewpoint-independent or allocentric memory, results from human lesion studies have been less conclusive. It is currently unclear whether disproportionate impairment in allocentric memory tasks reflects impairment of cognitive functions that are not sufficiently supported by regions outside the medial temporal lobe or whether the deficits observed in some studies are due to experimental factors. Here, we have investigated whether hippocampal contributions to spatial memory depend on the spatial references that are available in a certain behavioral context. Patients with medial temporal lobe lesions affecting systematically the right hippocampal formation performed a series of three oculomotor tasks that required memory of a spatial cue either in retinal coordinates or relative to a single environmental reference across a delay of 5000 ms. Stimulus displays varied the availability of spatial references and contained no complex visuo-spatial associations. Patients showed a selective impairment in a condition that critically depended on memory of the geometric relationship between spatial cue and environmental reference. We infer that regions of the medial temporal lobe, most likely the hippocampal formation, contribute to behavior in conditions that exceed the potential of viewpoint-dependent or egocentric representations. Apparently, this already applies to short-term memory of simple geometric relationships and does not necessarily depend on task difficulty or integration of landmarks into more complex representations. Deficient memory of basic geometric relationships may represent a core deficit that contributes to impaired performance in allocentric spatial memory tasks.     

Complementary Roles of the Hippocampus and the Dorsomedial Striatum during Spatial and Sequence-Based Navigation Behavior

We investigated the neural bases of navigation based on spatial or sequential egocentric representation during the completion of the starmaze, a complex goal-directed navigation task. In this maze, mice had to swim along a path composed of three choice points to find a hidden platform. As reported previously, this task can be solved by using two hippocampal-dependent strategies encoded in parallel i) the allocentric strategy requiring encoding of the contextual information, and ii) the sequential egocentric strategy requiring temporal encoding of a sequence of successive body movements associated to specific choice points. Mice were trained during one day and tested the following day in a single probe trial to reveal which of the two strategies was spontaneously preferred by each animal. Imaging of the activity-dependent gene c-fos revealed that both strategies are supported by an overlapping network involving the dorsal hippocampus, the dorsomedial striatum (DMS) and the medial prefrontal cortex. A significant higher activation of the ventral CA1 subregion was observed when mice used the sequential egocentric strategy. To investigate the potential different roles of the dorsal hippocampus and the DMS in both types of navigation, we performed region-specific excitotoxic lesions of each of these two structures. Dorsal hippocampus lesioned mice were unable to optimally learn the sequence but improved their performances by developing a serial strategy instead. DMS lesioned mice were severely impaired, failing to learn the task. Our data support the view that the hippocampus organizes information into a spatio-temporal representation, which can then be used by the DMS to perform goal-directed navigation.     

Galanthamine plus estradiol treatment enhances cognitive performance in aged ovariectomized rats

We hypothesize that beneficial effects of estradiol on cognitive performance diminish with age and time following menopause due to a progressive decline in basal forebrain cholinergic function. This study tested whether galanthamine, a cholinesterase inhibitor used to treat memory impairment associated with Alzheimer's disease, could enhance or restore estradiol effects on cognitive performance in aged rats that had been ovariectomized in middle-age. Rats were ovariectomized at 16–17 months of age. At 21–22 months of age rats began receiving daily injections of galanthamine (5 mg/day) or vehicle. After one week, half of each group also received 17ß-estradiol administered subcutaneously. Rats were then trained on a delayed matching to position (DMP) T-maze task, followed by an operant stimulus discrimination/reversal learning task. Treatment with galanthamine + estradiol significantly enhanced the rate of DMP acquisition and improved short-term delay-dependent spatial memory performance. Treatment with galanthamine or estradiol alone was without significant effect. Effects were task-specific in that galanthamine + estradiol treatment did not significantly improve performance on the stimulus discrimination/reversal learning task. In fact, estradiol was associated with a significant increase in incorrect responses on this task after reversal of the stimulus contingency. In addition, treatments did not significantly affect hippocampal choline acetyltransferase activity or acetylcholine release. This may be an effect of age, or possibly is related to compensatory changes associated with long-term cholinesterase inhibitor treatment. The data suggest that treating with a cholinesterase inhibitor can enhance the effects of estradiol on acquisition of a DMP task by old rats following a long period of hormone deprivation. This could be of particular benefit to older women who have not used hormone therapy for many years and are beginning to show signs of mild cognitive impairment. Potential mechanisms for these effects are discussed.     

The shark Chiloscyllium griseum can orient using turn responses before and after partial telencephalon ablation

This study assessed spatial memory and orientation strategies in Chiloscyllium griseum. In the presence of visual landmarks, six sharks were trained in a fixed turn response. Group 1 started from two possible compartments approaching two goal locations, while group 2 started from and approached only one location, respectively. The learning criterion was reached within 9 ± 5.29 (group 1) and 8.3 ± 3.51 sessions (group 2). Transfer tests revealed that sharks had applied a direction strategy, possibly in combination with some form of place learning. Without visual cues, sharks relied solely on the former. To identify the underlying neural substrate(s), telencephalic were lesioned and performance compared before and after surgery. Ablation of the dorsal and medial pallia only had an effect on one shark (group 1), indicating that the acquisition and retention of previously gained knowledge were unaffected in the remaining four individuals. Nonetheless, the shark re-learned the task. In summary, C. griseum can utilize fixed turn responses to navigate to a goal; there is also some evidence for the use of external visual landmarks while orienting. Probably, strategies can be used alone or in combination. Neither the dorsal nor medial pallium seems to be responsible for the acquisition and processing of egocentric information.     

大脑前额叶是怎样处理空间信息的

我们的大脑可能使用多个参考系来处理空间信息,比如使用"自我为中心的参考系"和"以大环境为参考系"来处理空间信息。灵长类大脑前额叶位于大脑皮层额叶的前端,尽管对前额叶在脑高级功能中的作用谁都不会怀疑,但很多具体的细节还是不甚清楚,比如背侧大脑前额叶在处理工作记忆信息时,是否处理所有的空间工作记忆信息?该文首先回顾对前额叶的研究情况,然后讨论背侧前额叶在处理自我为中心的空间信息中的作用,最后指出背侧前额叶仅对自我为中心的空间信息处理负责,而与大环境为中心的空间信息处理无关。     

Effects of Context on Visuomotor Interference Depends on the Perspective of Observed Actions

Visuomotor interference occurs when the execution of an action is facilitated by the concurrent observation of the same action and hindered by the concurrent observation of a different action. There is evidence that visuomotor interference can be modulated top-down by higher cognitive functions, depending on whether own performed actions or observed actions are selectively attended. Here, we studied whether these effects of cognitive context on visuomotor interference are also dependent on the point-of-view of the observed action. We employed a delayed go/no-go task known to induce visuomotor interference. Static images of hand gestures in either egocentric or allocentric perspective were presented as “go” stimuli after participants were pre-cued to prepare either a matching (congruent) or non-matching (incongruent) action. Participants performed this task in two different cognitive contexts: In one, they focused on the visual image of the hand gesture shown as the go stimulus (image context), whereas in the other they focused on the hand gesture they performed (action context). We analyzed reaction times to initiate the prepared action upon presentation of the gesture image and found evidence of visuomotor interference in both contexts and for both perspectives. Strikingly, results show that the effect of cognitive context on visuomotor interference also depends on the perspective of observed actions. When focusing on own-actions, visuomotor interference was significantly less for gesture images in allocentric perspective than in egocentric perspective; when focusing on observed actions, visuomotor interference was present regardless of the perspective of the gesture image. Overall these data suggest that visuomotor interference may be modulated by higher cognitive processes, so that when we are specifically attending to our own actions, images depicting others’ actions (allocentric perspective) have much less interference on our own actions.     

Tetrahydroxystilbene glucoside improves learning and (or) memory ability of aged rats and may be connected to the APP pathway

The aim of this study is to evaluate the protective effects of 2,3,5,4'-tetrahydroxystilbene-2-O-β-D-glucoside (TSG) on learning and (or) memory deficit in aged rats, as well as to explore the possible connection between TSG and the β-amyloid precursor protein (APP) pathway. Sprague-Dawley rats were randomly divided into a young control group (age, 4?months), an aged control group (age, 22?months), and a TSG-treated group (age, 22?months). TSG at doses of 50?mg·kg(-1)·day(-1) was intragastrically administered to 22-month-old rats for 4?weeks. The learning and (or) memory ability was measured using the Morris water maze (MWM) test, and the mRNA and protein expression of APP pathway proteins was measured by real-time polymerase chain reaction (RT-PCR) and Western blot, respectively. The aged rats exhibited obvious learning and (or) memory deficit when compared with the young rats, but TSG treatment significantly improved the learning and (or) memory ability in the aged rats, as noted from the MWM test. RT-PCR and Western blot analysis showed an increase in the expression of beta-site APP cleaving enzyme 1 (BACE1) and A Disintegrin And Metalloproteinase 17 (ADAM17) in aged rats, and a decrease in ADAM10; however, TSG treatment significantly increased the mRNA and protein expression of ADAM10 (p?< 0.01, compared with aged control rats). These results provide solid evidence for the therapeutic effect of TSG on age-related cognitive impairment, especially spatial learning and memory deficit. TSG might exert this effect through the APP pathway, although further studies on the topic are required.     

Repeated treatment with cholecystokinin octapeptide improves maze performance in aged Fischer 344 rats.

Previous studies have shown that sulfated cholecystokinin octapeptide (CCK-8S) can improve learning in adult rodents when administered systemically or into the central nucleus of amygdala. Here we analyzed the effect of repeated intraperitoneal (i.p.) injection of CCK-8S on the performance of 26-month-old Fischer 344 rats in different versions of the Morris water maze and in a rota-rod test of motor coordination. Old rats were injected daily with different doses of CCK-8S (0.32 to 8.0 microg/kg; IP) 10 min before the behavioral tests. Control groups included vehicle-injected old and adult (3-month-old) F 344 rats. To control for a possible development of tolerance to the behavioral effects of repeated CCK-8S administration, groups of aged rats were included which were subjected to an acute rather than a repeated CCK injection schedule. The repeated administration of CCK-8S did not influence the performance of the old rats in the hidden-platform version of the maze. In addition, the acute treatment with CCK-8S failed to modify navigation performance in this task, suggesting that drug-tolerance may not account for the lack of behavioral effects seen after repeated CCK-8S injection. During the "probe trial", the percentage of animals per group, which swam exactly across the former platform site, was markedly increased in aged rats treated repeatedly with 1.6 microg/kg CCK-8S. This might be indicative of improved retention of the prior platform location and/or a higher resistance of the learned escape response to extinction. The specificity of the effect of CCK-8S on processes related to spatial learning and memory is supported by the lack of effect on motor performance.