Functionally dissociating aspects of event memory: the effects of combined perirhinal and postrhinal cortex lesions on object and place memory in the rat

Reciprocal interactions between the hippocampus and the perirhinal and parahippocampal cortices form core components of a proposed temporal lobe memory system. For this reason, the involvement of the hippocampus in event memory is thought to depend on its connections with these cortical areas. Contrary to these predictions, we found that NMDA-induced lesions of the putative rat homologs of these cortical areas (perirhinal plus postrhinal cortices) did not impair performance on two allocentric spatial tasks highly sensitive to hippocampal dysfunction. Remarkably, for one of the tasks there was evidence of a facilitation of performance. The same cortical lesions did, however, disrupt spontaneous object recognition and object discrimination reversal learning but spared initial acquisition of the discrimination. This pattern of results reveals important dissociations between different aspects of memory within the temporal lobe. Furthermore, it shows that the perirhinal-postrhinal cortex is not a necessary route for spatial information reaching the hippocampus and that object familiarity-novelty detection depends on different neural substrates than do other aspects of event memory.     

The effect of excitotoxic lesions centered on the hippocampus or perirhinal cortex in object recognition and spatial memory tasks.

Rats with bilateral ibotenic acid lesions centered on the hippocampus (HPC) or perirhinal cortex (PRC) and sham-operated controls were tested in a series of object recognition and spatial memory tasks. Both HPC and PRC rats displayed reduced habituation in a novel environment and were impaired in an object-location task. HPC rats were severely impaired in both the reference and working-memory versions of the water maze and radial arm maze tasks. In contrast, although PRC rats displayed mild deficits in the reference memory version of the water maze and radial arm maze tasks, they were markedly impaired in the working-memory version of both the tasks. These findings demonstrate that under certain conditions both the HPC and PRC play a role in the processing of spatial memory. Further investigation of these conditions will provide important new insights into the role of these structures in memory processes. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Interaction of frontal and perirhinal cortices in visual object recognition memory in monkeys

Monkeys were trained preoperatively in visual object recognition memory. The task was delayed matching-to-sample with lists of trial-unique randomly generated visual stimuli in an automated apparatus, and the stimuli were 2D visual objects made from randomly generated coloured shapes. We then examined the effect of either: (i) disconnecting the frontal cortex in one hemisphere from the perirhinal cortex in the contralateral hemisphere by crossed unilateral ablations; (ii) disconnecting the magnocellular portion of the mediodorsal (MDmc) thalamic nucleus in one hemisphere from the perirhinal cortex in the contralateral hemisphere; or (iii) bilaterally ablating first the amygdala, then adding fornix transection, then finally perirhinal cortex ablation. We found that both frontal/perirhinal and MDmc/perirhinal disconnection had a large effect on visual object recognition memory, whereas both amygdalectomy and the addition of fornix transection had only a mild effect. We conclude that the frontal lobe needs to interact with the perirhinal cortex within the same hemisphere for visual object recognition memory, but that routes through the amygdala and hippocampus are not of primary importance.     

Place memory is intact in rats with perirhinal cortex lesions.

Two experiments compared the effects of bilateral lesions of the hippocampal formation (HPC) or perirhinal cortex (PRh) on rats' performance of an allocentric spatial working memory task—delayed matching-to-place (DMTP) in a water maze. DMTP trials consisted of paired swims, and the hidden platform was moved to a new location on each trial. Performance was assessed with intervals between the first and second swim (i.e., retention delays) of 4, 30, 120, and 300 s. The rats received extensive presurgery training in Experiment 1 and no presurgery training in Experiment 2. In both experiments, rats with HPC lesions displayed DMTP deficits at all delays, taking longer and swimming farther to find the platform on the second swims than did sham-operated controls. By contrast, rats with PRh lesions displayed normal DMTP acquisition and performance. The results suggest that, unlike the functions of HPC, those of PRh are not critical for allocentric spatial working memory. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Selective neurotoxic amygdala lesions in monkeys disrupt reactivity to food and object stimuli and have limited effects on memory.

Monkeys with bilateral neurotoxic amygdala lesions and normal monkeys were administered tests of emotional reactivity, recognition memory, and reward association memory. There were 3 main findings. First, monkeys with amygdala lesions performed differently than normal monkeys on initial administrations of the emotional reactivity tests and on retests that were given 21-23 months after surgery. Second, they performed like normal monkeys on tests of recognition memory. Third, they were initially impaired on a test of reward association memory, but they were not impaired on a retest that was given 16 months after surgery. These findings underscore the role of the amygdala in aspects of emotional reactivity and reward association memory, but not in recognition memory. In addition, at least some of the behavioral effects of amygdala damage can be long lasting. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Rhinal cortex lesions and object recognition in rats.

Tested 11 male rats with bilateral lesions of lateral entorhinal cortex and perirhinal cortex on a nonrecurring-items delayed nonmatching-to-sample (DNMS) task resembling the one that is commonly used to study object recognition (OR) in monkeys. The rats were tested at retention delays of 4, 15, 60, 120, and 600 sec before and after surgery. After surgery, they displayed a delay-dependent deficit: They performed normally at the 4-sec delay but were impaired at delays of 15 sec or longer. The addition of bilateral amygdala lesions did not increase their DNMS deficits. The present finding of a severe DNMS deficit following rhinal cortex damage is consistent with the authors' previous finding that bilateral lesions of the hippocampus cause only mild DNMS deficits in rats unless there is also damage to rhinal cortex (D. G. Mumby et al, 1992). These findings add to accumulating evidence that the rhinal cortex, but not the amygdala, plays a critical role in OR. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Lesions of the rat perirhinal cortex spare the acquisition of a complex configural visual discrimination yet impair object recognition.

Rats with perirhinal cortex lesions were sequentially trained in a rectangular water tank on a series of 3 visual discriminations, each between mirror-imaged stimuli. When these same discriminations were tested concurrently, the rats were forced to use a configural strategy to solve the problems effectively. There was no evidence that lesions of the perirhinal cortex disrupted the ability to learn the concurrent configural discrimination task, which required the rats to learn the precise combination of stimulus identity with stimulus placement (“structural” learning). The same rats with perirhinal cortex lesions were also unimpaired on a test of spatial working memory (reinforced T maze alternation), although they were markedly impaired on a new test of spontaneous object recognition. For the recognition test, rats received multiple trials within a single session in which on every trial, they were allowed to explore 2 objects, 1 familiar, the other novel. On the basis of their differential exploration times, rats with perirhinal cortex lesions showed very poor discrimination of the novel objects, thereby confirming the effectiveness of the surgery. The discovery that bilateral lesions of the perirhinal cortex can leave configural (structural) learning seemingly unaffected points to a need to refine those models of perirhinal cortex function that emphasize its role in representing conjunctions of stimulus features. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Neurotoxic lesions of the rat perirhinal cortex fail to disrupt the acquisition of performance of tests of allocentric spatial memory.

Rats with neurotoxic lesions of the perirhinal cortex (n = 9) were compared with sham controls (n = 14) on a working memory task in the radial am maze. Rats were trained under varying levels of proactive interference and with different retention intervals. Finally, performance was assessed when the maze was switched to a novel room. None of these manipulations differentially impaired rats with perirhinal lesions. Rats were next trained on delayed matching-to-place in the water maze. Even with retention delays of 30 min, there was no evidence of a deficit. Although interactions between the perirhinal cortex and hippocampus may be important for integrating object-place information, the perirhinal cortex is often not necessary for tasks that selectively tax allocentric spatial memory. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Excitotoxic lesions centered on perirhinal cortex produce delay-dependent deficits in a test of spatial memory

The purpose of the study was to assess developments in the theory of mind suggested by changes in the organization of cognitive verb extensions during the elementary school years. Adults and 3rd- and 5th-grade children were provided with a set of mental activity scenarios and were asked to select the best verbs from a list of cognitive verbs that might apply to each scenario. Changes in organization were assessed by examining overlapping uses of cognitive verbs in different contexts. There were 3 major changes with development: (a) the understanding of the role of memory in input functions increased, (b) the interrelatedness of memory- and comprehension-related verbs increased, and (c) the importance of cognitive certainty and uncertainty engaged by constructive processing verbs increased. Together, these findings suggest that a constructivist theory of mind develops in later childhood.     

The effects of NMDA lesions centered on the postrhinal cortex on spatial memory tasks in the rat.

Rats with bilateral N-methyl-D-aspartate lesions centered on the postrhinal cortex (POR) and sham lesions were tested in a series of spatial memory tasks. The POR-lesioned rats were significantly impaired compared with sham rats in the reference memory version of both the water maze and radial arm maze tasks and in the standard radial arm maze working memory task. The POR-lesioned rats displayed a delay-independent impairment in the working memory versions of the water maze and in a delayed nonmatching-to-place (DNMP) version of the radial arm maze task. The POR-lesioned rats were also impaired in a DNMP procedure conducted in the T-maze. These findings indicate that the POR has a delay-independent role in the processing of spatial information. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Lesions of rat perirhinal cortex exacerbate the memory deficit observed following damage to the fimbria-fornix.

Rats that had received bilateral lesions of the perirhinal cortex, fimbria-fornix, combined lesions of both these structures, or sham operations were tested on an object-guided delayed non-match-to-sample task. Perirhinal lesioned and fimbria-fornix lesioned rats were moderately impaired when delay intervals of 30 s or more were introduced between the sample and test phases of the experiment. Animals with combined lesions displayed a considerably greater impairment than animals with lesions of either structure alone. The combined lesioned animals were severely impaired in the initial acquisition of the task and displayed a profound memory deficit at delay intervals of greater than 4 s. These results emphasize the importance of the perirhinal cortex to memory function and suggest that the perirhinal cortex and the hippocampal formation may function interactively in the execution of memory processes. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The Von Restorff effect in visual object recognition memory in humans and monkeys. The role of frontal/perirhinal interaction

This study reports the development of a new, modified delayed matching to sample (DMS) visual recognition memory task that controls the relative novelty of test stimuli and can be used in human and nonhuman primates. We report findings from normal humans and unoperated monkeys, as well as three groups of operated monkeys. In the study phase of this modified paradigm, subjects studied lists of two-dimensional visual object stimuli. In the test phase each studied object was presented again, now paired with a new stimulus (a foil), and the subject had to choose the studied item. In some lists one study item (the novel or isolate item) and its associated foil differed from the others (the homogenous items) along one stimulus dimension (color). The critical experimental measure was the comparison of the visual object recognition error rates for isolate and homogenous test items. This task was initially administered to human subjects and unoperated monkeys. Error rates for both groups were reliably lower for isolate than for homogenous stimuli in the same list position (the von Restorff effect). The task was then administered to three groups of monkeys who had selective brain lesions. Monkeys with bilateral lesions of the amygdata and fornix, two structures that have been proposed to play a role in novelty and memory encoding, were similar to normal monkeys in their performance on this task. Two further groups--with disconnection lesions of the perirhinal cortex and either the prefrontal cortex or the magnocellular mediodorsal thalamus--showed no evidence of a von Restorff effect. These findings are not consistent with previous proposals that the hippocampus and amygdala constitute a general novelty processing network. Instead, the results support an interaction between the perirhinal and frontal cortices in the processing of certain kinds of novel information that support visual object recognition memory.     

Memory impairment on a delayed non-matching-to-position task after lesions of the perirhinal cortex in the rat.

Previous research conducted in monkeys and rats has established that the perirhinal cortex is critically involved in object- or stimulus-recognition memory, whereas other research suggests this region may contribute to memory for object discriminations. These findings do not rule out the possibility that the perirhinal cortex plays a more general role in memory. The present experiment addressed whether selective lesions of the perirhinal cortex would result in a delay-dependent deficit on a test of memory that did not involve stimulus recognition or object memory. Rats with bilateral perirhinal lesions were tested on a delayed non-matching-to-position task. Lesions of the perirhinal cortex did not interfere with acquisition or performance at short (0–4 s)-delay intervals, but lesions did impair performance at longer delays. It is suggested that the perirhinal cortex is involved in maintaining representations of trial-specific information over time. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

A peculiar pattern of temporal involvement of rat perirhinal cortex in memory processing.

By means of the fully reversible tetrodotoxin inactivation technique, perirhinal cortex (PC) mnemonic function was investigated in rats trained to a passive avoidance response (PAR). It was shown that PC functional integrity is necessary during PAR acquisition, during late and very late consolidation (from 24 hr up to 192 hr after the training session), and during retrieval. An unexpected finding was that the PC was not involved in the early consolidation period. Thus the PC may play a relatively simple relay or connective role during acquisition, but its very late and very long consolidative involvement may indicate a peculiar function in consolidation and possibly in the storage of the PAR engram. The results are discussed in terms of the mnemonic characteristics of other neural sites (amygdala, hippocampus, and entorhinal cortex) involved in the same learning process. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effects of muscarinic blockade in perirhinal cortex during visual recognition

Stimulus recognition in monkeys is severely impaired by destruction or dysfunction of the perirhinal cortex and also by systemic administration of the cholinergic-muscarinic receptor blocker, scopolamine. These two effects are shown here to be linked: Stimulus recognition was found to be significantly impaired after bilateral microinjection of scopolamine directly into the perirhinal cortex, but not after equivalent injections into the laterally adjacent visual area TE or into the dentate gyrus of the overlying hippocampal formation. The results suggest that the formation of stimulus memories depends critically on cholinergic-muscarinic activation of the perirhinal area, providing a new clue to how stimulus representations are stored.     

Disruptive effects of posttraining perirhinal cortex lesions on conditioned fear: Contributions of contextual cues.

Lesions placed in the rostral perirhinal cortex (rPRh) after fear conditioning interfere with the expression of conditioned fear responses elicited by auditory and visual conditioned stimuli when these stimuli are presented in a context that differs from the conditioning context. The present study examined whether lesions of the rPRh have similar effects when animals are tested in the conditioning context. Two days after male rats received classical fear conditioning, involving the pairing of an auditory CS with footshock, bilateral electrolytic lesions were produced in the rPRh. Five days later conditioned freezing behavior was measured during a 60-s exposure to the CS in a novel context and then 1 hr later in the conditioning context. There were 3 major findings: rPRh-lesioned Ss froze significantly less than controls to the CS in the novel context, thus confirming previously reported findings. rPRh-lesioned Ss also froze less than controls to the CS in the conditioning context, but froze significantly more to the CS in the conditioning than in the novel context, suggesting that at least part of the deficit in the novel context is due to the absence of contextual cues. Ss with rPRh lesions froze significantly less than controls to the conditioning context itself.… (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Monkeys with rhinal cortex damage or neurotoxic hippocampal lesions are impaired on spatial scene learning and object reversals

Rhesus monkeys (Macaca mulatta) with lesions of the rhinal cortex or parahippocampal gyrus (made by aspiration) or hippocampus (made with ibotenic acid) and unoperated controls were tested on object discrimination and reversal, place discrimination and reversal, and spatial scene learning to determine the contribution of these temporal lobe structures to these forms of learning and memory. Rhinal cortex lesions produced a severe deficit in object reversal learning; hippocampal lesions produced a milder deficit. Monkeys with rhinal cortex removals and those with hippocampal lesions were equally impaired on spatial scene learning. None of the lesions impaired place discrimination or reversal. These results argue against the idea that the mnemonic contributions of the rhinal cortex and hippocampus are limited to object and spatial domains, respectively.     

Effects of amygdaloid and amygdaloid-hippocampal lesions on object recognition and spatial working memory in rats.

Neurotoxic lesions of the amygdala did not affect the postoperative acquisition of a nonspatial test of object recognition (delayed nonmatching to sample) even when retention delays were increased from 0 sec to 20 or 60 sec, or when test stimuli were deliberately repeated within a session. Although these amygdaloid lesions did not alter forced-choice spatial alternation, they slightly increased neophobic responses to novel foods and environments. In contrast, combined amygdalohippocampal (A?+?H) lesions impaired performance on the object recognition task when the retention intervals were increased beyond 0 sec and when test stimuli were repeated within a session. The A?+?H rats were also severely impaired on the spatial alternation task, and they showed reduced neophobia. Comparisons with a previous study show that damage to the amygdala or hippocampus does not affect object recognition, whereas A?+?H damage produces clear deficits. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Recognition impaired and association intact in the memory of monkeys after transection of the fornix.

Three rhesus monkeys with transection of the fornix were compared with 3 operated control monkeys in 4 memory tasks. They were tested repeatedly at each task until a stable level of performance was achieved. Ss with transection of the fornix were severely impaired in the 3 tasks that tested recognition memory and unimpaired in a test of pure associative memory which was very similar in all but the essential respects to one of the recognition tasks. It is suggested that damage to the hippocampal system in monkeys causes an anterograde amnesia comparable to that observed in human patients with similar lesions and consisting in a specific deficit of recognition memory. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The hippocampus and long-term object memory in the rat

Animal models of amnesia have yielded many insights into the neural substrates of different types of memories. Some very important aspects of memory, however, have been ignored in research using experimental animals. For example, to examine long-term memory investigators traditionally have relied on measures of information acquisition, which stand in contrast to the measures of retention commonly used in work with humans. We have recently developed a behavioral paradigm that measures both the acquisition and long-term retention of object discriminations, and found a selective retention impairment in rats with entorhinal-hippocampal disconnection (Vnek et al., 1995). The present study was designed to determine whether direct damage to the hippocampus likewise would lead to a selective deficit in the retention of visual discriminations. Rats with aspiration lesions of the dorsal hippocampus, rats with neocortical control lesions, and normal controls were trained on three object discrimination problems and then retrained 3 weeks later to measure retention. All animals showed the same level of performance during the training (acquisition) phase of testing, but the performance of animals with dorsal hippocampal injury fell below that of controls during retraining (retention). Taken together, these and our earlier results suggest that the hippocampus and anatomically related structures are particularly important for retaining visual discriminations over long delay intervals. These findings may clarify the role of the hippocampus in nonspatial memory.