Lesions of the dorsal subiculum and the dorsal hippocampus impaired pattern separation in a task using distinct and overlapping visual stimuli

The contribution of the dorsal subiculum (DS) and of the dorsal hippocampus (DH) to memory for distinct and overlapping visual stimuli was examined. Rats with selective lesions of the DS or the DH were compared to sham-operated rats on a delayed matching-to-place task guided by distal visual cues in a modified radial-arm maze. Overlapping distal visual cues could be perceived from three arm entrances (adjacent arms) and a unique set of distal cues were more likely to be seen from the other two arm entrances (distinct arms). Rats with DS lesions were impaired on trials with baited adjacent arms, but not on trials with baited distinct arms. Rats with DH lesions were impaired on both types of trials. These results suggest that the DS and the DH are necessary for pattern separation and that they may have different contributions to memory.     

Flexible cue use in food-caching birds

An animal’s memory may be limited in capacity, which may result in competition among available memory cues. If such competition exists, natural selection may favor prioritization of different memory cues based on cue reliability and on associated differences in the environment and life history. Food-caching birds store numerous food items and appear to rely on memory to retrieve caches. Previous studies suggested that caching species should always prioritize spatial cues over non-spatial cues when both are available, because non-spatial cues may be unreliable in a changing environment; however, it remains unclear whether non-spatial cues should always be ignored when spatial cues are available. We tested whether mountain chickadees (Poecile gambeli), a food-caching species, prioritize memory for spatial cues over color cues when relocating previously found food in an associative learning task. In training trials, birds were exposed to food in a feeder where both spatial location and color were associated. During subsequent unrewarded test trials, color was dissociated from spatial location. Chickadees showed a significant pattern of inspecting feeders associated with correct color first, prior to visiting correct spatial locations. Our findings argue against the hypothesis that the memory of spatial cues should always take priority over any non-spatial cues, including color cues, in food-caching species, because in our experiment mountain chickadees chose color over spatial cues. Our results thus suggest that caching species may be more flexible in cue use than previously thought, possibly dependent upon the environment and complexity of available cues.     

Virtual human analogs to rodent spatial pattern separation and completion memory tasks

Spatial pattern separation (SPS) and spatial pattern completion (SPC) have played an increasingly important role in computational and rodent literatures as processes underlying associative memory. SPS and SPC are complementary processes, allowing the formation of unique representations and the reconstruction of complete spatial environments based on partial spatial information. We present two novel computerized navigational tasks as human analogs of well-established rat SPS and SPC tasks. Results from these tasks show that human participants are sensitive to increasing SPS and SPC demands. Specifically, memory accuracy decreased with decreasing separation distance between target and foil locations in the SPS task and with decreasing number of distal spatial cues in the SPC task. These tasks set the stage for valuable future directions, including the use of these tasks with imaging and clinical populations.     

工作记忆中的部分线索效应:任务呈现方式的影响

以往研究主要在长时记忆中考察部分线索效应,很少关注工作记忆中的部分线索效应及其作用机制。本研究采用项目再认任务,考察了工作记忆中提供部分学习项目作为提取线索,对存储在工作记忆中的已有表征的影响。结果发现：有、无部分线索试次分组呈现时,相较于无部分线索条件,有部分线索条件下再认正确率和d'降低,β升高,反应时间延长;有、无部分线索试次随机混合呈现时,有部分线索条件下再认正确率降低,β升高,但反应时间并无显著延长。结果表明：工作记忆中部分线索的提供降低了目标项目的表征强度;研究结果可用提取抑制假说解释,但工作记忆中部分线索的作用可能受注意资源有限性制约。     

Acute Ethanol Administration Impairs Spatial Performance While Facilitating Nonspatial Performance in Rats

Acute ethanol administration produces learning and memory impairments similar to those found following lesions to the hippocampal system in rats. For example, both ethanol and hippocampal lesions impair performance on spatial learning and memory tasks while sparing performance on many nonspatial learning and memory tasks. Lesions to the hippocampal system can also alter the nature of the information that the animal uses to guide its behavior, from using spatial information to using individual cues. In the present experiment, rats were trained, while sober, to navigate on an eight-arm radial arm maze to a specific arm for food reward. During training, the rewarded arm was always in the same specific location and contained well-defined cues. After the rat learned the task, a memory test was conducted under different doses of ethanol (0.0 g/kg [saline control], 1.0, 1.5, or 2.0 g/kg, intraperitoneal). On the test day the maze was rotated so that the cued arm was 90 degrees to the right of its original position. During testing, intact rats showed a significant bias to approach the place where they had been previously rewarded, even though the cue was no longer located there. Acute ethanol administration dose dependently reduced approaches to the rewarded place. However, ethanol administration did not result in increases in random choices; rather, it resulted in a dose-dependent increase in approaches to the cued arm, now in a new location. These results extend previous research showing that acute ethanol administration and lesions to the hippocampal system produce similar effects on learning and memory in rats.     

The role of the hippocampus in the retrieval of a spatial location

Based on computational models of the hippocampus, it has been suggested that a possible mechanism for memory retrieval is pattern completion, wherein an autoassociative network recalls previous patterns of activity given noisy or degraded cues. However, there are few behavioral data examining pattern completion per se in the hippocampus. Here, we present a study in which rats were tested on a spatial location retrieval paradigm, each trial of which consisted of a sample and choice phase. During the sample phase, rats were trained to displace an object in one of 15 possible locations to retrieve a food reward and return to the start-box on a cheeseboard maze. The object was then removed and the same location was re-baited for the choice phase. The rats' accuracy in returning to the correct location was recorded. On test trials, visual extramaze cues, vestibular cues, or both were manipulated to assess pattern completion in normal rats. Subjects were then randomly assigned to receive a cortical control, a sham, or a dorsal and ventral hippocampal lesion and were retested on the task. Control and unoperated rats were able to perform the task when visual extramaze or vestibular cues were reliable, but not when they were manipulated. Rats with hippocampal lesions were impaired in the baseline condition, as well as during all manipulations. These results support the hypothesis that the hippocampus supports the retrieval of a spatial location, possibly through a process of pattern completion.     

Contrasting effects of lateral striate and superior colliculus lesions on visual discrimination performance in rhesus monkeys.

Rhesus monkeys with lesions of lateral striate cortex, monkeys with superior colliculus lesions, and unoperated monkeys were tested for retention of a preoperatively acquired pattern discrimination. The three groups of monkeys were then tested in two-choice, color, color discrimination tests, one involving varying degrees of stimulus-response (S-R) separation and the other, administered several months later, involving various directions of S-R separations. The monkeys were also tested in a series of two-choice pattern discriminations, following each of which they were tested for relearning when the patterns were masked with bars or circles. The monkeys with lateral striate lesions were moderately retarded in retention of the pattern discrimination, whereas those with superior colliculus lesions were not. The monkeys with colliculus lesions, but not those with lateral striate lesions, were impaired in both S-R separation tests, which demonstrates that their deficit was not transient or solely due to a difficulty in shifting the gaze in one direction. The lateral striate monkeys, unlike those with colliculus lesions, were dificient in relearning discriminations between masked patterns. These findings suggest that superior colliculus and striate cortex may be involved in two different aspects of attention: respectively, shifting attention (and orientation) from one spatial locus to another and maintaining attention on fixated stimuli. Alternative interpretations of the effects of the lesions, based on their retinotopic loci, are discussed.     

Spatial Memory and Aging: Performance on a Human Analog of the Morris Water Maze

Rodent studies demonstrate parallel age-related changes in spatial memory and the hippocampal formation. Converging cognitive, neuropsychological, and neurobiological evidence suggests similar changes in humans, although these correlates have not been studied in the same individuals. The purpose of the current project was to develop and validate a human analog of a rodent spatial memory task for future use in correlative studies of spatial memory and brain structure and function. Younger and older healthy adults studied the location of a target relative to distal cues in a large tent-like enclosure. Group performances were similar for the practice trial, which could be solved verbally, suggesting similar abilities to remember the configuration of multiple stimuli in a large space. However, on subsequent trials, which depended more upon spatial memory, older adults were impaired relative to their younger counterparts.     

The effects of lesions to the rat hippocampus or rhinal cortex on olfactory and spatial memory: retrograde and anterograde findings

The role of the hippocampal system in retrograde and anterograde amnesia was investigated by using a novel olfactory-guided paradigm and a traditional test of spatial learning. In the retrograde study, rats were trained on a sequence of two-choice olfactory discriminations in the weeks prior to receiving neurotoxic lesions of the hippocampus or aspiration lesions of the perirhinal-entorhinal cortex. Memory tests for preoperatively learned discriminations revealed no statistical impairment for subjects with damage to the hippocampus on a problem learned remote in time from surgery (i.e., 4 weeks +) or on the two recently learned discriminations (i.e., 1–3 weeks prior to surgery). The performance of subjects with perirhinal-entorhinal damage provided an important comparison for subjects with specific hippocampal lesions. Despite showing intact memory for the remotely learned problem, perirhinalentorhinal damage resulted in numerically (although not significantly) weaker performance on postoperative tests of retention for the discriminations learned in the 3 weeks prior to surgery. In the anterograde portion of the study, long-term memory for newly acquired discriminations was spared in subjects with damage to the hippocampus, whereas subjects in the perirhinal-entorhinal lesion group again showed the weakest memory performance on these tests of 5-day retention. Postoperative water maze learning was uniformly impaired in subjects with damage to the hippocampus and perirhinalentorhinal cortex, thus confirming the effect of these lesions and supporting the involvement of these brain areas in spatial processes. These findings further dissociate the specific involvement of the hippocampus in tasks of a spatial-relational nature versus nonrelational tasks, such as discrimination learning and recognition memory (e.g., Duva et al., 1997; Eichenbaum, 1997; Eichenbaum, Schoenbaum, Young, & Bunsey, 1996). Moreover, the results suggest that damage to the hippocampus itself does not contribute to retrograde or anterograde memory impairments for all types of information, whereas the data suggest a more important role for the perirhinal-entorhinal cortex in recognition memory, irrespective of modality.     

Medial dorsal thalamic lesions and working memory in the rat

Pigmented rats of the DA strain with either radiofrequency or ibotenic acid lesions of the thalamic nucleus medialis dorsalis were postoperatively given nonspatial and spatial tests of working memory. In the nonspatial task, delayed nonmatching-to-sample, rats with both types of thalamic lesions showed acquisition impairments. The subgroup of rats with nucleus medialis dorsalis lesions that were able to reach the acquisition criterion did, however, perform normally when the retention interval was extended to 60 s. In the spatial task, delayed forced-alternation, rats were tested with differing retention intervals and with both spaced and massed trials. Damage to nucleus medialis dorsalis had no effect on acquisition or on spaced trials, but a slight deficit was found in the animals with radiofrequency lesions under the massed trial condition. Much clearer deficits were, however, present in those animals in which the lesion extended appreciably into the anterior thalamic nuclei. The findings indicate that while cellular damage to nucleus medialis dorsalis may disrupt learning, some impairments in tests of spatial working memory attributed to this nucleus may reflect damage to the adjacent anterior thalamic nuclei.     

Enhanced long-term and impaired short-term spatial memory in GluA1 AMPA receptor subunit knockout mice: Evidence for a dual-process memory model

The GluA1 AMPA receptor subunit is a key mediator of hippocampal synaptic plasticity and is especially important for a rapidly-induced, short-lasting form of potentiation. GluA1 gene deletion impairs hippocampus-dependent, spatial working memory, but spares hippocampus-dependent spatial reference memory. These findings may reflect the necessity of GluA1-dependent synaptic plasticity for short-term memory of recently visited places, but not for the ability to form long-term associations between a particular spatial location and an outcome. This hypothesis is in concordance with the theory that short-term and long-term memory depend on dissociable psychological processes. In this study we tested GluA1^−/− mice on both short-term and long-term spatial memory using a simple novelty preference task. Mice were given a series of repeated exposures to a particular spatial location (the arm of a Y-maze) before their preference for a novel spatial location (the unvisited arm of the maze) over the familiar spatial location was assessed. GluA1^−/− mice were impaired if the interval between the trials was short (1 min), but showed enhanced spatial memory if the interval between the trials was long (24 h). This enhancement was caused by the interval between the exposure trials rather than the interval prior to the test, thus demonstrating enhanced learning and not simply enhanced performance or expression of memory. This seemingly paradoxical enhancement of hippocampus-dependent spatial learning may be caused by GluA1 gene deletion reducing the detrimental effects of short-term memory on subsequent long-term learning. Thus, these results support a dual-process model of memory in which short-term and long-term memory are separate and sometimes competitive processes.     

Cue usage in memory for location when orientation is fixed

In previous research, it was demonstrated that including one or three cues surrounding a circular field had no effect on spatial memory for dot locations when the field's orientation was fixed, but that there were very large effects when orientation varied across trials (Fitting, Wedell, & Allen, 2007). In four new experiments, we explored the use of external cues in the fixed orientation environment, using 0, 4, 8, or 24 cues and manipulating task difficulty. In Experiments 1-3, the angular bias data supported the use of four quadrant-based prototypes regardless of cue condition, but there were clear cue effects on radial prototype locations. Increasing the number of cues enhanced accuracy of spatial memory for targets closer to cues. In Experiment 4, we severely challenged memory by using multiple targets and a filled delay before estimation. Doing so demonstrated an effect of cues on the categorical structuring of memory. Collectively, findings indicate that when orientation is fixed, cues bolster fine-grain memory, but that they only alter the default categorical scheme when memory demands are high.     

时序信息和空间信息在工作记忆中的分离存储

采用相对新近性判断范式（judgments of relative recency）,通过三个实验探讨了工作记忆中时序信息和空间信息的存储方式及其关系。实验一比较了有无空间线索两种条件下时序信息的记忆绩效,结果发现,有无空间线索并不影响对时序信．E-的记忆。实验二和实验三通过控制刺激呈现的视野范围和减少呈现位置的不确定性来利化空间线索,结果表明,时序信息的记忆绩效也不受空间线索的影响。由此推论,工作记忆中的时序信息和空间信息是分离编码存储的,加入空间线索并不能提高时序信息的记忆绩效。     

Hierarchical structures: chunking by food type facilitates spatial memory

Three experiments assessed the ability of male Sprague-Dawley rats to organize the spatial locations of different food types in a hierarchical manner to maximize the efficiency of working memory. Independent groups were exposed, on a 12-arm radial maze, to baiting arrangements varying in the stability of the pattern and type of food used as bait. Training rats with stable, differentiable baiting arrangements produced increased accuracy in choice performance, hierarchically ordered patterns of choice selection, slower growth of proactive interference when trials were massed, and the learning of the geometrical relations among food types independent of other extramaze cues. Such findings are strong evidence of the rat's ability to encode and use local cues for navigation, based on properties of the reinforcer. The application of a chunking strategy may provide for more efficient use of working memory by facilitating information storage, recall, or resetting mechanisms.     

Disruption of delayed memory for a sequence of spatial locations following CA1- or CA3-lesions of the dorsal hippocampus

Axon-sparing neurotoxic lesions of CA1 or CA3 were produced in the dorsal hippocampus to test dissociative lesion effects on spatial working memory for sequential items. Rats were required to remember four different sections sequentially presented on a newly devised maze (i.e., Tulum maze) during a study phase. Each section was cued by a unique object that was specifically associated with each location within the section during the study phase. Following a 15-s delay and during the test phase, rats were required to revisit the location within a section randomly chosen among the previously visited sections in the absence of the cued object. Both CA1 and CA3 lesions similarly disrupted accurate relocation of a previously visited place. However, differential effects of the CA1 and CA3 lesions were observed in serial position curves. CA3-lesions disrupted performance for the first three serial positions, but did not disrupt performance for the last serial position (recency). In contrast, CA1-lesions disrupted performance for all serial positions. The results suggest that temporal separation of spatial memory may depend on the conjoint function of CA1 and CA3 of the hippocampus with a disruption of a spatial pattern completion process following CA3 lesions and a disruption of a temporal pattern separation process following a CA1 lesion.     

Effect of small cue-response separation on pattern discrimination in macaques (Macaca fuscata and M. mulatta)

In order to elucidate the nature of the effect of small cue-response separations on pattern discriminations by monkeys, three studies were performed. When training on a pattern discrimination with a cue-response separation was discontinued during performance at the chance level, there was no saving on the rate of learning a second task (with identical cues but a different cue-response separation) relative to the performance of naive control animals. By contrast, when training was discontinued at a performance level a little better than chance, there was significant saving on learning a second task. After learning the second task, a third task with new pattern cues was learned, with marked saving on the duration of performance at the chance level. The results indicate that during the initial stage of performance at the chance level, monkeys do not attend to cues if there is even a small separation between the cue and the response site.     

Anterograde and retrograde amnesia of place discrimination in retrosplenial cortex and hippocampal lesioned rats

Retrograde and anterograde amnesic effects of excitotoxic lesions of the rat retrosplenial cortex (RS) and hippocampus (HPC) were investigated. To test retrograde amnesia, rats were trained with two-arm place discrimination in a radial maze 4 wk and 1 d before surgery with a different arm pair, respectively. In the retention test 1 wk after surgery, both lesion groups showed temporally ungraded retrograde amnesia. To test anterograde amnesia, animals were trained after surgery to discriminate three arm pairs successively within a day, and then after interposition of 1- to 4-wk intervals, one of these pairs, respectively, was tested for retention. RS-lesioned rats could acquire these pairs of place discriminations rapidly but showed a retention interval-dependent impairment in the retention test. Conversely, HPC-lesioned rats took more sessions to acquire these pairs than did the control group, and their retention was approximately 70% of correct performance regardless of retention interval. Results suggest that RS and HPC have different roles in spatial memory and that RS is important for remote memory process.     

A revised spatial serial learning and memory procedure using Corsi's Block-tapping apparatus

The purpose of this study was to use Corsi's Block Tapping Test as a spatial analog of Benton's Serial Digit Learning Test, using the cognitive neuroscience approach utilized in the California Verbal Learning Test. 60 normal participants, ages 19-52 years, were included and administered an 8-block sequence for 9 trials or until they recalled the entire sequence for 3 consecutive errorless trials. The score was the number of blocks tapped in the correct serial order. An interference trial was administered. Following a 10-min. delay, free recall of the original sequence, cued recall, and recognition measures were obtained. Retroactive interference was significant, but no proactive interference emerged. Scores showed a strong primacy effect. Most participants who learned the sequence to the criterion of three successive errorless trials recalled the sequence after the 10-min. delay. Scores on the cued recall and recognition trials tended to support their validity as less demanding retrieval tasks. The use of this spatial learning and memory procedure allows finer discriminations among nonverbal memory deficits and may facilitate direct comparisons with scores on verbal memory tasks such as Serial Digit Learning and the California Verbal Learning Test.     

Spatial and nonspatial escape strategies in the Barnes maze

The Barnes maze is a spatial memory task that requires subjects to learn the position of a hole that can be used to escape the brightly lit, open surface of the maze. Two experiments assessed the relative importance of spatial (extra-maze) versus proximal visible cues in solving the maze. In Experiment 1, four groups of mice were trained either with or without a discrete visible cue marking the location of the escape hole, which was either in a fixed or variable location across trials. In Experiment 2, all mice were trained with the discrete visible cue marking the target hole location. Two groups were identical to the cued-target groups from Experiment 1, with either fixed or variable escape locations. For these mice, the discrete cue either was the sole predictor of the target location or was perfectly confounded with the spatial extra-maze cues. The third group also used a cued variable target, but a curtain was drawn around the maze to prevent the use of spatial cues to guide navigation. Probe trials with all escape holes blocked were conducted to dissociate the use of spatial and discrete proximal cues. We conclude that the Barnes maze can be solved efficiently using spatial, visual cue, or serial-search strategies. However, mice showed a strong preference for using the distal room cues, even when a discrete visible cue clearly marked the escape location. Importantly, these data show that the cued-target control version of the Barnes maze as typically conducted does not dissociate spatial from nonspatial abilities.     

Teaching autistic children to respond to simultaneous multiple cues

A number of studies have shown that autistic children tend to learn new discriminations by responding to only a restricted number of available cues and that this may be responsible for some of their abnormal behavior. Therefore, this investigation assessed the feasibility of teaching autistic children to respond to multiple cues. The results showed that four autistic children could learn a conditional discrimination requiring them to discriminate a multiple-cue complex from each of its two component cues. However, the autistic children did not learn this discrimination in the same manner as normal children. In the early trials, the autistics responded at a higher level to one of the two component cues. Only after many trials did the autistics respond equally on the basis of both component cues. The results of an initial attempt to teach a general set to respond to multiple cues showed that, when an autistic child was taught a series of successive conditional discriminations, the child eventually learned a set to approach new discriminations by responding equally on the basis of both component cues. The results are discussed in terms of understanding and treating autistic children's abnormal development.