Hippocampal damage and exploratory preferences in rats: memory for objects, places, and contexts

Rats have a natural tendency to spend more time exploring novel objects than familiar objects, and this preference can be used as an index of object recognition. Rats also show an exploratory preference for objects in locations where they have not previously encountered objects (an index of place memory) and for familiar objects in contexts different from those in which the objects were originally encountered (an index of context memory). In this experiment, rats with cytotoxic lesions of the hippocampal formation were tested on all three versions of the novelty-preference paradigm, with a 5-min retention interval between the familiarization and test phases. Rats with sham lesions displayed a novelty preference on all three trial types, whereas the rats with hippocampal lesions displayed a novelty preference on Object trials but did not discriminate between the objects on Place trials or Context trials. The findings indicate that hippocampal damage impairs memory for contextual or spatial aspects of an experience, whereas memory for objects that were part of the same experience are left relatively intact.     

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.     

The role of the dorsal and ventral hippocampus in olfactory working memory

Olfactory working memory and pattern separation for odor information was assessed in male rats using a matching-to-sample for odors paradigm. The odor set consisted of a five aliphatic acids with unbranched carbon chains that varied from two- to six-carbons in length. Each trial consisted of a sample phase followed by a choice phase. During the sample phase, rats would receive one of five different odors. Fifteen seconds later during the choice phase one of the previous odors was presented simultaneously side by side with a different odor that was based on the number of aliphatic acids that varied in the carbon chains from two- to six-carbons in length and rats were allowed to choose between the two odors. The rule to be learned in order to receive a food reward was to always choose the odor that occurred during the study phase. Odor separations of 1, 2, 3 or 4 were selected for each choice phase and represented the carbon chain difference between the study phase odor and the test phase odor. Once an animal reached a criterion of 80–90% correct across all temporal separations based on 40 trials, rats received a control, dorsal hippocampal, or ventral hippocampal lesion and were retested on the task. On postoperative trials, only the ventral hippocampal lesion group was impaired relative to both control and dorsal hippocampal groups groups. There were no effects on odor pattern separation. All groups of rats could discriminate between the odors. The data suggest that the ventral hippocampus, but not dorsal hippocampus, supports working memory for odor information.     

Septal area lesions impair spatial working memory in homing pigeons (Columba livia)

The septo-hippocampal system in birds resembles that of mammals, motivating research into the function of the avian hippocampus while surprisingly little attention has been given to the septum. To investigate a possible role of the avian septum in memory, the effects of septal area lesions on a spatial working memory (SpWM) task was tested in homing pigeons. After preoperative training on an analogue eight-arm (feeders) radial maze, now sham-operated control and septal lesioned pigeons were then trained again on the same task of locating the four feeders on the test phase of a trial that were not baited during the sample phase of a trial. During the test phase of a working memory trial, septal lesioned pigeons, compared to both their own preoperative performance and the performance of the controls, required significantly more choices to locate the four baited feeders not baited during the sample phase of a trial, and they made significantly fewer correct responses to the now baited feeders on their first four choices. The results demonstrate that, like its mammalian counterpart, the avian septum plays an important role in SpWM, suggesting that at least some functional properties of the septum are evolutionarily conserved in birds and mammals.     

Memory for frequency in rats: role of the hippocampus and medial prefrontal cortex

On a radial arm maze rats were tested for frequency memory of specific spatial locations, a task that presumably involves the coding of temporal information. On any trial during the study phase rats were allowed to visit three different spatial locations only once and one spatial location twice. During the test phase the rats were given a choice between a spatial location that had been visited once and spatial location that had been visited twice. The rats were reinforced for selecting the twice-visited spatial location. The number of spatial locations between a repetition (lag) was varied from one to three. After extensive training rats displayed memory for frequency only for a lag of three spatial locations, i.e., they displayed a repetition lag effect. Animals then received control, medial prefrontal cortex, or hippocampal lesions. Upon subsequent retests control rats continued to display frequency memory, but animals with medial prefrontal cortex or hippocampal lesions displayed a marked impairment. These data support the idea that both the hippocampus and medial prefrontal cortex code temporal order information.     

Memory for temporal order of new and familiar spatial location sequences: role of the medial prefrontal cortex

Rats with medial prefrontal cortex or sham control lesions were tested on an eight-arm radial maze task to examine memory for the temporal order of a variable and a constant sequence of spatial locations as a function of temporal distance. During the study phase of each trial, rats were allowed to visit each of eight arms once in an order that was randomly selected or fixed for that trial. The test phase required the rats to choose which of two arms occurred earlier in the sequence of arms visited during the study phase. The arms selected as test arms varied according to temporal distance (0, 2, 4, or 6) or the number of arms that occurred between the two test arms in the study phase. For the variable sequences based on new information, control rats showed an increasing temporal distance function. Relative to control rats, medial prefrontal cortex-lesioned rats displayed a temporal order memory deficit across all distances. For the constant sequence based on familiar information, control rats performed well across all distances. Relative to controls, the medial prefrontal cortex-lesioned rats displayed a performance deficit. The results support the idea that the medial prefrontal cortex contributes to mnemonic operations associated with temporal order for new and familiar spatial location information.     

Comparing the effects of two correction procedures on human acquisition of sequential behavior patterns

Thirty-one college undergraduates learned to touch abstract stimuli on a computer screen in arbitrarily designated “correct” sequential orders. Four sets of seven stimuli were used; the stimuli were arrayed horizontally on the screen in random sequences. A correct response (i.e., touching first the stimulus designated as first) resulted in that stimulus appearing near the top of the screen in its correct sequential position (left to right), and remaining there until the end of the trial. Incorrect responses (i.e., touching a stimulus out of sequence) terminated the trial. New trials displayed either the same sequence as the one on which an error had occurred (same-order correction procedure), or a new random sequence (new-order correction procedure). Whenever all responses occurred in the correct sequence, the next trial displayed a new random sequence. Each phase ended when five consecutive correct response sequences occurred. Initially, the same-order correction procedure increased control by the position as well as by the shape of the stimuli; also, it produced more errors, more total trials, more trials to mastery, and more individual patterns of reacquisition than were produced by the new-order procedure.     

Memory systems in the rat: effects of reward probability,context, and congruency between working and reference memory

The interaction of working and reference memory was studied in rats on an eight-arm radial maze. In two experiments, rats were trained to perform working memory and reference memory tasks. On working memory trials, they were allowed to enter four randomly chosen arms for reward in a study phase and then had to choose the unentered arms for reward in a test phase. On reference memory trials, they had to learn to visit the same four arms on the maze on every trial for reward. Retention was tested on working memory trials in which the interval between the study and test phase was 15 s, 15 min, or 30 min. At each retention interval, tests were performed in which the correct WM arms were either congruent or incongruent with the correct RM arms. Both experiments showed that congruency interacted with retention interval, yielding more forgetting at 30 min on incongruent trials than on congruent trials. The effect of reference memory strength on the congruency effect was examined in Experiment 1, and the effect of associating different contexts with working and reference memory on the congruency effect was studied in Experiment 2.     

Hypnosis and interrogative suggestibility

An attempt was made to induce memory errors through the use of misleading questioning in hypnosis. Subjects heard a short newslike story and gave initial free recall for the story details, then 4 days later were given three free recall trials: prior to hypnosis, following hypnotic induction and suggestion for enhanced memory, and after hypnosis was terminated. During hypnosis subjects were also twice interrogated with either misleading or objective questions for the story details. Accurate memory increased over the three free recall trials for all subjects regardless of hypnotizability. In recognition testing, subjects given misleading questions during the interrogation gave fewer correct responses, had more errors-in-fact as well as forgetting, and showed an increase in yielding to interrogative suggestibility over trials than subjects given objective questions. All subjects subsequently confabulated more information on the final awake free recall trial as a result of errors introduced during hypnotic interrogation process. These results help to clarify the inherent dangers in relying on hypnosis to enhance memory.     

Rats depend on habit memory for discrimination learning and retention

We explored the circumstances in which rats engage either declarative memory (and the hippocampus) or habit memory (and the dorsal striatum). Rats with damage to the hippocampus or dorsal striatum were given three different two-choice discrimination tasks (odor, object, and pattern). These tasks differed in the number of trials required for learning (~10, 60, and 220 trials). Dorsal striatum lesions impaired discrimination performance to a greater extent than hippocampal lesions. Strikingly, performance on the task learned most rapidly (the odor discrimination) was severely impaired by dorsal striatum lesions and entirely spared by hippocampal lesions. These findings suggest that discrimination learning in the rat is primarily supported by the dorsal striatum (and habit memory) and that rats engage a habit-based memory system even for a task that takes only a few trials to acquire. Considered together with related studies of humans and nonhuman primates, the findings suggest that different species will approach the same task in different ways.     

Sequence effects by non-predictive arrow cues

Previous studies have found that attention orienting is influenced by the orienting processes of previous trials in a spatial cueing paradigm. This study mainly investigated whether this sequence effect could happen for a non-predictive arrow cue and whether it was influenced by the cue-target SOAs in previous and current trials. A significant sequence effect was observed for arrow cues even when voluntary control was not required, and it was significantly influenced by the SOAs of previous trials. The present results support the automatic memory check hypothesis and may reflect some temporal characteristics of the memory mechanism in sequential processes. In addition, contrary to the previous findings, we found an overall response facilitation following a catch trial, suggesting that the influence of preceding catch trials may be sensitive to experimental contexts.     

Perseverative interference with object-in-place scene learning in rhesus monkeys with bilateral ablation of ventrolateral prefrontal cortex

Surgical disconnection of the frontal cortex and inferotemporal cortex severely impairs many aspects of visual learning and memory, including learning of new object-in-place scene memory problems, a monkey model of episodic memory. As part of a study of specialization within prefrontal cortex in visual learning and memory, we tested monkeys with bilateral ablations of ventrolateral prefrontal cortex in object-in-place scene learning. These monkeys were mildly impaired in scene learning relative to their own preoperative performance, similar in severity to that of monkeys with bilateral ablation of orbital prefrontal cortex. An analysis of response types showed that the monkeys with lesions were specifically impaired in responding to negative feedback during learning: The post-operative increase in errors was limited to trials in which the first response to each new problem, made on the basis of trial and error, was incorrect. This perseverative pattern of deficit was not observed in the same analysis of response types in monkeys with bilateral ablations of the orbital prefrontal cortex, who were equally impaired on trials with correct and incorrect first responses. This may represent a specific signature of ventrolateral prefrontal involvement in episodic learning and memory.     

Neural mediation of memory for time: Role of the hippocampus and medial prefrontal cortex

Within the context of the neurobiology of attribute model, memory for the temporal attribute is composed of at least three features—memory for duration, memory for succession, or temporal order, and memory for past and future time perspective within a dual-based (data and knowledge) memory system. Research aimed at testing the assumption that the hippocampus and interconnected neural circuits mediate the temporal attribute within the data-based memory system and the prefrontal cortex and interconnected neural circuits mediate the temporal attribute within the knowledge-based memory system in animals and humans is reviewed. The research indicates that (1) memory for the duration feature of the temporal attribute is mediated by the hippocampus, but not prefrontal cortex, in both animals and humans, (2) memory for the temporal order feature of the temporal attribute based on new information is subserved by both the hippocampus and the prefrontal cortex, but that based on prior knowledge or the ability to use prior knowledge is supported only by prefrontal cortex, and not the hippocampus, in both animals and humans, and (3) memory for the past (time perspective) feature of the temporal attribute is mediated by the hippocampus, whereas memory for the future (time perspective) feature of the temporal attribute is supported by the prefrontal cortex in both animals and humans. There is a clear parallel between animals and humans in terms of hippocampal and prefrontal cortex mediation of the temporal attribute, supporting the assumption of evolutionary continuity. There is support for a greater involvement of the hippocampus in comparison with the prefrontal cortex in mediating temporal attribute information within the data-based memory system. Conversely, there is support for a greater involvement of the prefrontal cortex in comparison with the hippocampus in mediating temporal attribute information within the knowledge-based memory system. Future research needs to concentrate on the development of new paradigms to measure memory for different temporal features and to uncover the critical neural circuits that subserve these temporal features.     

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.     

Selective lesions of the dentate gyrus produce disruptions in place learning for adjacent spatial locations

The hippocampus (HPP) plays a known role in learning novel spatial information. More specifically, the dentate gyrus (DG) hippocampal subregion is thought to support pattern separation, a mechanism for encoding and separating spatially similar events into distinct representations. Several studies have shown that lesions of the dorsal DG (dDG) in rodents result in inefficient spatial pattern separation for working memory; however, it is unclear whether selective dDG lesions disrupt spatial pattern separation for reference memory. Therefore, the current study investigated the role of the dDG in pattern separation using a spatial reference memory paradigm to determine whether the dDG is necessary for acquiring spatial discriminations for adjacent locations. Male Long-Evans rats were randomly assigned to receive bilateral intracranial infusions of colchicine or saline (control) into the dDG. Following recovery from surgery, each rat was pseudo-randomly assigned to an adjacent arm or separate arm condition and subsequently tested on a place-learning task using an eight-arm radial maze. Rats were trained to discriminate between a rewarded arm and a nonrewarded arm that were either adjacent to one another or separated by a distance of two arm positions. Each rat received 10 trials per day and was tested until the animal reached a criterion of nine correct choices out of 10 consecutive trials across 2 consecutive days of testing. Both groups acquired spatial discriminations for the separate condition at similar rates. However, in the adjacent condition, dDG lesioned animals required significantly more trials to reach the learning criterion than controls. The results suggest that dDG lesions decrease efficiency in pattern separation resulting in impairments in the adjacent condition involving greater overlap among the distal cues. Conversely, in the separate condition, there was less overlap among distal cues during encoding and less need for pattern separation. These findings provide further support for a critical role for the dDG in spatial pattern separation by demonstrating the importance of a processing mechanism that is capable of reducing interference among overlapping spatial inputs across a variety of memory demands.     

Object recognition memory and the rodent hippocampus

In rodents, the novel object recognition task (NOR) has become a benchmark task for assessing recognition memory. Yet, despite its widespread use, a consensus has not developed about which brain structures are important for task performance. We assessed both the anterograde and retrograde effects of hippocampal lesions on performance in the NOR task. Rats received 12 5-min exposures to two identical objects and then received either bilateral lesions of the hippocampus or sham surgery 1 d, 4 wk, or 8 wk after the final exposure. On a retention test 2 wk after surgery, the 1-d and 4-wk hippocampal lesion groups exhibited impaired object recognition memory. In contrast, the 8-wk hippocampal lesion group performed similarly to controls, and both groups exhibited a preference for the novel object. These same rats were then given four postoperative tests using unique object pairs and a 3-h delay between the exposure phase and the test phase. Hippocampal lesions produced moderate and reliable memory impairment. The results suggest that the hippocampus is important for object recognition memory.Recognition memory refers to the ability to judge a previously encountered item as familiar and depends on the integrity of the medial temporal lobe (Squire et al. 2007). Tasks that assess recognition memory (and object recognition memory in particular) have become increasingly useful tools for basic and preclinical research investigating the neural basis of memory (Winters et al. 2008). Perhaps the best known of these tasks is the novel object recognition task (NOR) (also known as the visual paired-comparison task in studies with humans and monkeys).Studies of the NOR task in humans with hippocampal damage (McKee and Squire 1993; Pascalis et al. 2004) and in monkeys with selective damage to the hippocampus (Pascalis and Bachevalier 1999; Zola et al. 2000; Nemanic et al. 2004) have resulted in clear and consistent findings. Damage limited to the hippocampus is sufficient to produce impaired recognition memory (Squire et al. 2007, Box 1). In rats and mice, the NOR task has become particularly popular and is currently a benchmark task for assessing recognition memory. Yet despite its widespread use in rodents, the findings are rather mixed. For example, in the rat, although there is agreement that the perirhinal cortex is critically important for normal NOR performance, there is less agreement about the hippocampus (for review, see Winters et al. 2008). Although some of the discrepancies between studies may be attributed to differences in lesion size and in the length of the retention delay (Broadbent et al. 2004), these factors cannot account for all the findings (Squire et al. 2007).Whereas most studies have investigated the effects of hippocampal lesions on postoperative NOR performance, there is also interest in the effects of hippocampal lesions on memory for previously encountered objects. For a number of tasks, hippocampal lesions produce temporally graded retrograde amnesia, such that memory acquired recently is impaired and memory acquired more remotely is spared (for review, see Squire et al. 2004; Frankland and Bontempi 2005). In the case of the single study of retrograde memory that has involved the NOR task, recognition memory was impaired when a 5-wk interval intervened between training and hippocampal surgery (Gaskin et al. 2003). It remains possible that memory might be spared if a longer delay was imposed between training and surgery.The aim of the present study was to assess both the anterograde and retrograde effects of hippocampal lesions on recognition memory using the NOR task. To thoroughly assess the effects of hippocampal lesions we used (1) large groups of animals, (2) multiple tests of NOR memory, (3) a scoring method that allowed object preference to be determined on a second-by-second basis during the recognition tests, and (4) a novel training protocol that permitted the evaluation of recognition memory even after a retention interval as long as 10 wk.     

Performance on trials without knowledge results (KR) in reduced relative frequency presentations of KR

Following Salmoni, Schmidt, & Walter's (1984) discussion of knowledge of results (KR) as a variable influencing learning, the effect of varying relative frequency of KR while holding absolute number of trials constant was examined. In two experiments, the same treatment groups were compared in acquisition, retention (after 2 min and 24 hr), and on their pattern of responses on the sequence of no-KR trials following a KR trial. In Experiment 1, differences between groups in acquisition were consistent with the number of KR trials received, and there were no differences between groups in either of the retention conditions. Experiment 2 replicated Experiment 1 with a more difficult task. There were no between-group differences in acquisition. In Retention 1, the 100% and 33% relative frequency groups outperformed the less frequent KR groups, whereas in Retention 2, this trend was reversed. The findings from Experiment 2 provide qualified support for the hypothesis that reduced relative frequency of KR in acquisition facilitates performance in retention. The pattern of responses on the sequence of no-KR trials following a KR trial were consistent with Adams' (1971) perceptual-trace decay hypothesis.     

Neural substrates of successful working memory and long-term memory formation in a relational spatial memory task

Working memory (WM) tasks may involve brain activation actually implicated in long-term memory (LTM). In order to disentangle these two memory systems, we employed a combined WM/LTM task, using a spatial relational (object-location) memory paradigm and analyzed which brain areas were associated with successful performance for either task using fMRI. Critically, we corrected for the performance on the respective memory task when analyzing subsequent memory effects. The WM task consisted of a delayed-match-to-sample task assessed in an MRI scanner. Each trial consisted of an indoor or outdoor scene in which the exact configuration of four objects had to be remembered. After a short delay (7–13 s), the scene was presented from a different angle and spatial recognition for two objects was tested. After scanning, participants received an unexpected subsequent recognition memory (LTM) task, where the two previously unprobed objects were tested. Brain activity during encoding, delay phase and probe phase was analyzed based on WM and LTM performance. Results showed that successful WM performance, when corrected for LTM performance, was associated with greater activation in the inferior frontal gyrus and left fusiform gyrus during the early stage of the maintenance phase. A correct decision during the WM probe was accompanied by greater activation in a wide network, including bilateral hippocampus, right superior parietal gyrus and bilateral insula. No voxels exhibited supra-threshold activity during the encoding phase, and we did not find any differential activity for correct versus incorrect trials in the WM task when comparing LTM correct versus LTM incorrect trials.     

提取方式对相继记忆效应的影响

采用学习－测验（自由回忆和再认）研究范式和事件相关电位方法,研究图形的相继记忆效应（Dm效应）。14名大学生作为研究被试,根据其测验成绩将图片分为记住和未记住两类,对相应编码过程的ERPs进行分析。结果表明：⑴行为上,再认的平均击中率显著高于自由回忆;⑵脑电活动上,在刺激出现后400~700ms编码过程中记住项目的ERPs更正于未记住项目的ERPs;同时两种测验方式Dm效应的脑区分布不同,自由回忆主要分布在额区,再认主要分布在中央区和顶区,且在500~600ms自由回忆有左侧优势。这些结果表明,两种提取方式对Dm效应有不同的影响,这一结果预示自由回忆和再认的编码过程可能有不同的神经生理机制。     

A procedure for generating differential "sample" responding without different exteroceptive stimuli

Sidman (1994, 2000) suggested that responses as well as stimuli can join equivalence classes, a hypothesis difficult to test because differential responding typically requires different stimuli. The present experiments describe a procedure with pigeons that avoids this potential confounding effect. In Experiment 1, spacing two responses 3 s apart (a differential-reinforcement-of-low-rate [DRL] schedule) to a white stimulus on some trials produced food or the comparison stimuli in a matching task, whereas pecking 10 or more times with no temporal restrictions (a fixed-ratio [FR] schedule) produced the same effect on other trials. Completing the alternative (unscheduled) requirement terminated the white stimulus and repeated the trial. Following such errors, pigeons learned to switch to the alternative response pattern on the repeat trials. In addition, the correct response pattern functioned as a conditional cue for comparison choice. In Experiment 2, mixed DRL-FR training was preceded by two-sample/two-alternative matching-to-sample with DRL and FR sample-response requirements. In a subsequent transfer test in which the correct response pattern to white served as the sample, pigeons preferentially chose the comparison previously reinforced following that pattern in the baseline task. This "unsignaled response" procedure may be useful for assessing whether differential responses can be members of acquired equivalence classes.