Perspectives on object-recognition memory following hippocampal damage: lessons from studies in rats
Introduction
One of the routine memory abilities impaired in amnesic patients is the capacity to recognize the people and objects they have encountered since the onset of their amnesia. Recognition memory can be described in different ways, but it is generally regarded as the ability to discriminate the familiarity of things previously encountered [3]. Recognition occurs in all sensory domains, but most research into the anatomical bases of recognition impairments in human amnesics is concerned with visual recognition.
Attempts to reproduce visual-recognition impairments like those displayed by amnesic patients have played a central role in animal models of amnesia during the past two and a half decades, and until recent years most of the emphasis was on describing how damage to the hippocampal formation (HPC; including the dentate gyrus, Ammon's horn, and subiculum) could impair visual recognition, either alone or in combination with damage to other medial-temporal-lobe structures. Today, it is clear that the role of the HPC in recognition memory has been overemphasized, and most investigators are now looking elsewhere for an explanation of the recognition impairment displayed by amnesic patients. This includes many of those who study clinical populations and those who study animal models of amnesia. But there is still debate about the consequences of focal hippocampal damage for visual recognition.
This review examines studies in which object-recognition memory, a subcategory of visual recognition, was assessed in rats after the HPC was made dysfunctional either by ablation or by fornix transection. It has two main goals: The first is to show that the findings from lesion studies in rats are fairly consistent in suggesting that HPC damage does not impair object-recognition memory. HPC damage might impair other memory abilities, but that issue will not be discussed.
The second goal of this review accounts for the focus on lesion studies in rats, and it is to counter the tendency to give somewhat marginal consideration to findings in rats when making inferences about the neuroanatomical bases of amnesia in humans. With a few exceptions, most discussions in the literature concerning animal models of amnesia emphasize findings in monkeys, while corresponding studies in rats are either ignored entirely, or given only secondary consideration. When the relevant findings in rats are cited, it is often merely to demonstrate the generalizability of results obtained in monkeys, rather than to point out sources of original evidence. It is hoped this review will show that studies with rats can provide unique information not ascertained from studies in monkeys.
Treatments that undoubtedly cause severe disruption of hippocampal function, including HPC ablation or fornix transection, have failed to impair performance on object-recognition tasks in rats under a wide range of conditions. Not surprisingly, there are a few exceptions. But upon close scrutiny, some of those appear to be illusory in the extent to which they reflect true impairments of object recognition. Together, the preponderance of evidence from rats suggests that the hippocampus plays, at most, a very limited role in object-recognition, and perhaps none at all. A similar conclusion was reached in recent reviews of neuroanatomical studies of spatial and nonspatial recognition in rats [3], [34], [101].
The present review clarifies some important evidence that was either addressed only partially by those earlier reviews, or excluded altogether. It discusses new findings that have come to light in recent months, and considers some new perspectives that were not reflected in the earlier reviews. It purposely excludes several converging lines of evidence from studies using nonlesion methods. These exclusions are made because the question asked in this review is whether damage to the HPC impairs the ability to recognize an object. Only lesion experiments can directly address this question.
Broader reviews, like two of those just mentioned [3], [101], serve the essential purpose of tying together converging evidence from different approaches to studying brain-memory relations, including experimental lesions, electrophysiological recording, brain imaging, psychopharmacology, neurogenetics, neuroanatomical studies, and neuropsychological assessments of clinical cases and populations. Most if not all investigators depend upon reviews like that to get an idea of how their own findings fit with those of other researchers working on similar problems. But as the number of published studies using each approach continues to grow at an accelerated rate, those undertaking the more general reviews have no choice but to deal with an enormous literature by giving only summary descriptions of the findings from the individual studies that use each particular approach. The references to previous findings are sometimes misleading, because they exclude qualifying details that would only come from a closer examination of what was originally reported. This review focuses on only one approach to studying brain–memory relations, but the more limited scope allows for a more in-depth analysis of several key experiments. In this way, the present review differs from the earlier ones that addressed the broader questions concerning the role of the hippocampus in recognition memory [3], [101].
Recognition of different visual aspects of an experience can be distinguished psychologically, and also in brain circuitry. The question addressed in this review is specific to object-recognition memory—the ability to discriminate the familiarity of previously encountered objects. Thus, it excludes studies that examined the effects of HPC lesions on recognition of things like brightness cues, or visual features embedded in spatial arrays (e.g. distinctive patterns on the arms of a radial maze), or two-dimensional graphic images projected on a computer screen, notwithstanding the possibility that there may be important similarities in the brain circuitry required for recognizing these other types of visual stimuli and that underlying recognition of three-dimensional objects.
The controversy over the effects of HPC damage on object recognition is best appreciated in its historical context. It has origins in the 1950s with the discovery of global amnesia in humans after medial-temporal-lobe damage, and the subsequent development of animal models of amnesia in monkeys. The second main section of this paper provides a summary account of that story. During the past 15 years, a variety of behavioural methods for studying object-recognition memory in rats have been developed, thus providing a more accessible model and with it the means for more and larger-scale parametric studies on the effects of brain damage on object-recognition memory. The third main section describes the tasks that have been developed for rats and considers evidence that they involve recognition processes similar to those involved in the monkey versions. Section 4 reviews the studies conducted in rats that are relevant to the question of whether HPC damage impairs object recognition. Section 5 attempts to place the findings in rats into perspective, thus allowing a justified conclusion to be made about the consequences of HPC damage for object recognition.
Section snippets
Object recognition and monkey models of amnesia
The discovery of H.M.'s amnesia came at a time when most psychologists accepted Karl Lashley's proposition that memory traces are widely distributed throughout the cortex, rather than localized within particular structures. Lashley's experiments with animals had appeared to demonstrate that the degree of impairment on learning tasks was proportional to the amount of cortex damaged, but unrelated to the particular area of damage. The occurrence of severe and selective memory impairment in H.M.
Delayed matching and nonmatching-to-sample
During the latter half of the 1980s, several investigators were successful in adapting the DNMS task for use with rats [1], [59], [73], [93]. This broadened the comparative basis for drawing inferences about the anatomical bases of object recognition, because now the same experiments can be conducted in rats and monkeys. This has practical advantages, because compared with monkeys, the laboratory rat provides a more accessible model for most researchers, and therefore, facilitates the conduct
Object recognition following hippocampal damage in rats
The sections that follow provide a review of several studies conducted in rats that either expressly or implicitly tested the hypothesis that hippocampal damage impairs object-recognition memory. Each one involved permanent disruption of hippocampal functions, either by HPC ablation, fornix lesion, or transient forebrain ischemia. To the best of my knowledge, this is a comprehensive list of the relevant studies that have been described in published reports or in recent published abstracts.
HPC damage and performance on object-recognition tasks
Out of the 18 studies reviewed here that used the DNMS or DMS task to test the hypothesis that HPC damage impairs object recognition (Table 1), only two of them are relatively unassailable in having found convincing DNMS deficits [25], [115]. Two others reported results that could be construed as evidence of mild deficits under one experimental condition [74], [78], but when viewed in the context of what was found in the other conditions of the same experiments, it seems less likely that the
Conclusions
Much of the evidence that previously supported the hippocampalcentric view of memory and amnesia came from studies of object-recognition memory in monkeys with surgical lesions of the hippocampus that were confounded by damage to structures in the parahippocampal region. Studies in monkeys with more circumscribed lesions have still not determined whether focal hippocampal damage impairs object recognition. During the past 15 years, a variety of behavioural methods for studying
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