Dave G. Mumby

Perspectives on object-recognition memory following hippocampal damage: lessons from studies in rats.

One of the routine memory abilities impaired in amnesic patients with temporal-lobe damage is object-recognition memory--the ability to discriminate the familiarity of previously encountered objects. Reproducing this impairment has played a central role in animal models of amnesia during the past two decades, and until recent years most of the emphasis was on describing how hippocampal damage could impair object recognition. Today most investigators are looking outside the hippocampus to explain the impairment. This paper reviews studies of object-recognition memory in rats with hippocampal damage produced by ablation, fornix transection, or forebrain ischemia. Some new perspectives on previous findings reinforce the conclusion that damage to the hippocampus has little if any impact on the ability to recognize objects, while damage in some areas outside the hippocampus is far more effective. The few circumstances in which hippocampal damage can impair performance on object-recognition tasks are situations where ancillary abilities are likely to play a significant role in supporting task performance. Some of the factors that contributed to the origins and persistence of the hippocampalcentric view of object-recognition are considered, including lesion confounds, failure to distinguish between impaired task performance and impairment of a memory ability, and disproportionate attention to a few lesion studies in monkeys, even though the hypothesis was tested far more times in rats, under a greater variety of conditions, and rejected on nearly every occasion.

Retrograde amnesia after hippocampal damage: Recent vs. remote memories in two tasks

We review evidence from experiments conducted in our laboratory on retrograde amnesia in rats with damage to the hippocampal formation. In a new experiment reported here, we show that N‐methyl‐D‐aspartate (NMDA)‐induced hippocampal damage produced retrograde amnesia for both hidden platform and two‐choice visible platform discriminations in the Morris water task. For both problems there was a significant trend for longer training‐surgery intervals to be associated with worse retention performance. Little support is offered by our work for the concept that there is a process involving hippocampal‐dependent consolidation of memories in extrahippocampal permanent storage sites. Long‐term memory consolidation may take place within the hippocampus. The hippocampus may be involved permanently in storage and/or retrieval of a variety of relational and nonrelational memories if it was intact at the time of learning, even involving information which is definitely not affected in anterograde amnesia after hippocampal damage. Hippocampus 2001;11:27–42.

Impaired object recognition memory in rats following ischemia-induced damage to the hippocampus

Transient cerebral ischemia can produce irreversible neuronal damage and permanent learning and memory impairments in humans. This study examined whether ischemia-induced brain damage in rats results in impairments on the delayed nonmatching-to-sample (DNMS) task, a nonspatial recognition task analogous to tests on which amnesic patients display impairments. Male Wistar rats received either sham surgery or 20-min forebrain ischemia induced by bilateral carotid occlusion and hypotension. Four weeks after surgery, ischemic rats were significantly impaired in both learning and performing the DNMS task at retention intervals up to 5 min. Extensive presurgical training did not reduce this impairment. Observable cell loss in ischemic rats was limited to CA1 pyramidal neurons and a subset of cells in the dentate gyrus. The results indicate that ischemic damage to the hippocampus in rats results in recognition memory deficits similar to those produced by ischemic damage in humans.

Retrograde amnesia and selective damage to the hippocampal formation: memory for places and object discriminations

Using a within-subjects design, rats were trained on two place-memory problems and five object-discrimination problems at different intervals prior to receiving either ibotenate lesions of the hippocampal formation or sham surgery. Places # 1 and 2 were fixed-platform water-maze tasks that were run in different rooms and they were learned during the 14th and 2nd week before surgery, respectively. Object-discrimination problems # 1-5 were learned during the 13th, 10th, 7th, 4th, and 1st week before surgery, respectively. Rats with hippocampal lesions displayed impaired retention of both Place problems with no evidence of a temporal gradient to the impairment. In contrast to their retrograde place-memory deficits, the hippocampal rats displayed normal retention of the five object-discriminations that were learned before surgery. Hippocampal lesions had similar consequences for anterograde learning, as the lesioned rats were impaired in acquisition of a new water-maze problem that was run in a third room (Place #3), whereas they showed normal acquisition of two new object-discriminations. The findings indicate that the hippocampal formation is not required for long-term consolidation of information underlying accurate performance of object-discriminations, and that its critical role in memory for places persists for at least 14 weeks, and probably for as long as those memories exist.

Object-recognition memory is only mildly impaired in rats with lesions of the hippocampus and amygdala

Rats were trained on the nonspatial delayed nonmatching-to-sample task that we recently developed to mimic the task that is commonly used to study amnesia in monkeys. The rats were tested at retention delays of 4, 15, 60, 120, and 600 sec, both before and after surgery. Each experimental rat received bilateral lesions of the hippocampus, amygdala, or both. In comparison to no-surgery control rats, the rats in each of the three experimental groups were significantly and equally impaired only at the 600-sec delay. These findings indicate that neither separate nor combined lesions of the amygdala and hippocampus cause severe object-recognition impairments in pretrained rats.

Nonrecurring-items delayed nonmatching-to-sample in rats: A new paradigm for testing nonspatial working memory

Rats were trained on a nonrecurring-items delayed nonmatching-to-sample task, using a newly designed apparatus and a training protocol similar to that used in experiments on nonspatial working memory in humans and monkeys. On each trial, the rats were briefly presented with a sample object, which was presented again along with another object after a delay; the rats were rewarded with food if they chose the novel object. New stimuli were used on each trial. With delays of 4 sec between the sample and choice runs, the rats learned the task to 90% accuracy in less than 250 trials. When the delay was subsequently increased to 15, 60, 120, and 600 sec, the rats scored approximately 91%, 81%, 77%, and 57%, respectively. These results establish that rats are capable of excellent performance on a nonspatial working-memory task that is comparable to those commonly used in monkey models of amnesia, and they suggest that the nonrecurring-items delayed nonmatching-to-sample paradigm may prove valuable in modeling brain-damage-produced amnesia in rats.

Perirhinal cortex damage and anterograde object-recognition in rats after long retention intervals

Damage to the perirhinal cortex (PRh) in rats impairs anterograde object-recognition memory after retention intervals of up to several hours, but there is little direct evidence to link PRh function to object-recognition abilities after substantially longer intervals that span several days or weeks. We assessed the effects of PRh lesions on anterograde object recognition using a novel-object preference test, with retention intervals lasting 24 h and 3 weeks. The rats received multiple exposures to the sample object during the learning phase--5 min per day on 5 consecutive days. Control rats displayed a significant novel-object preference after both retention intervals, indicating recognition of the sample object, whereas the rats with PRh lesions displayed a significant preference after the 24-h interval, but not after the 3-week interval. When the learning phase of the trial was shortened to a single 5-min session, the PRh group was impaired in the 24-h condition. The findings indicate that the disruptive effects of PRh damage on anterograde object recognition persist over very long postlearning intervals. The results indicate further that object recognition impairments following PRh damage are not ubiquitous, and that learning conditions play a significant role in determining the subsequent recognition performance in rats with PRh damage.

Object familiarization and novel-object preference in rats

We investigated whether object familiarization was related to novel-object preference in the novel-object preference (NOP) test in rats. In Experiment 1, we found that no significant correlation existed between the time spent investigating 2 identical copies of a sample object and the degree of preference for a novel object. In Experiment 2, rats investigated 2 identical sample objects for a total of 5, 30, 60, 90 or 120s. Investigatory preference for the novel object was compared to chance expectancy as well as between the groups. Only the 90-s group and the 120-s group displayed above-chance investigatory preference for the novel object, but novel-object preference for these 2 groups did not differ from each other, suggesting that a minimal amount of sample object investigation is necessary for rats to develop a novel-object preference, beyond which no increase in novel-object preference was found. In Experiments 3 and 4, normal rats and rats with hippocampal lesions were given repeated test trials, with the same sample object presented with a different novel object, at 24-h and (Experiment 3) and 35-s intervals (Experiment 4). In both experiments, novel-object preference did not increase in magnitude with repeated sample object exposures, suggesting that increased familiarity with the sample object does not result in increased novel-object preference. Rats with lesions of the dorsal hippocampus showed an unreliable investigatory preference for the novel object. These results are discussed in terms of the potential limitations of the NOP test as a tool for the assessment of object-recognition memory in rats.

Memory deficits following lesions of hippocampus or amygdala in rat: Assessment by an object-memory test battery

We tested rats with bilateral lesions of the hippocampus or the amygdala on a battery of five object-memory tasks, which resemble those that have been used in the study of amnesia in humans and monkeys: (1) object discrimination, (2) discrimination reversal, (3) eight-pair concurrent object discrimination, (4) nonrecurring-items delayed nonmatching-to-sample (DNMS) with retention delays of 4, 15, 30, 60, and 120 sec and with lists of three, five, and seven samples, and (5) order discrimination. All testing was postsurgery. Relative to control rats, the rats with hippocampal lesions required more trials to master the object discrimination and the concurrent object discrimination. Rats with hippocampal lesions required about as many trials as did control rats to master DNMS at the 4-sec delay and displayed only mild deficits at the longest (120-sec) delay. Rats with amygdalar lesions required more trials to master the concurrent object discriminations than did controls, but significantly fewer than did rats with hippocampal lesions. They required more trials than did controls to master DNMS with a 4-sec delay; however, after they had done so, they continued to perform normally as the delay was increased. Neither lesion produced deficits on discrimination reversal, DNMS with lists, or order discrimination. While these findings demonstrate that the mnemonic effects of hippocampal and amygdalar lesions can be dissociated using a battery of object-memory tasks, they also suggest a limited role for these two structures in many object-memory abilities.

Enhanced context-dependency of object recognition in rats with hippocampal lesions.

Object recognition memory was assessed on a novel-object preference (NOP) task in rats with lesions of the hippocampal formation (HPC). The learning and test phases of NOP trials occurred in either the same context or in different contexts. When the learning and test contexts were the same, rats with HPC lesions performed like control rats, displaying a significant tendency to investigate a novel object more than a familiar sample object. When the test occurred in a context that was familiar but different from the learning context, performance was unaffected in control rats, but rats with HPC lesions no longer discriminated between the objects, and therefore showed no evidence of recognizing the sample object. When the test context was unfamiliar, novel-object preference in control rats was attenuated but still above chance levels, whereas rats with HPC lesions did not show a preference. The data suggest that the HPC is not critical for encoding or retrieving conjunctive representations of the context in which incidental learning occurs, whereas it plays an essential role in recognition of objects that are subsequently encountered in different contexts.