Crossed unilateral lesions of temporal lobe structures and cholinergic cell bodies impair visual conditional and object discrimination learning in monkeys

Monkeys with excitotoxic lesions of the CA1/subiculum region in the right hemisphere and with immunotoxic lesions of the cholinergic cells of the diagonal band in the left hemisphere were impaired on a visual conditional task. In this task, correct choice of one of two objects depends on which of two background fields both objects are presented against, irrespective of the spatial positions of the objects. They were not impaired on simple object or shape discrimination tasks. The pattern of impairments is the same as that seen after bilateral excitotoxic lesions of CA1/subiculum, implying that the diagonal band lesion disables the ipsilateral CA1/subiculum. It also argues that CA1/subiculum, sustained by its cholinergic input, is necessary for some forms of nonspatial conditional learning. Addition of an inferotemporal (IT) cortical ablation to the left hemisphere did not affect simple visual discrimination learning, although all the monkeys then failed to learn a new visual conditional task. This demonstrates that intact IT cortex in only one hemisphere is sufficient to sustain simple visual discrimination learning but implies that the cholinergic input and the inferotemporal cortical input to the hippocampus both contribute to visual conditional learning. The subsequent addition of an immunotoxic lesion of the basal nucleus of Meynert in the right hemisphere resulted in an additional impairment on a difficult shape discrimination. This argues that it is the cholinergic projection to the inferotemporal cortex, rather than to the rest of the cortex, which contributes to visual discrimination learning and memory.     

Neglect of memory after dopaminergic lesions in monkeys

Crossed unilateral dopaminergic lesions of the nigrostriatal bundle and unilateral inferotemporal cortex ablations (DA x IT lesions) in marmoset monkeys produced impaired retention of object discriminations first learnt before, or after, the DA lesion but no impairment on new learning of the same type of task. Retention testing of a pre-operatively learned task was given after new learning of a different task so impairment cannot be attributed to improvement with practice or spontaneous recovery. We argue that the DA lesion produces a form of intentional neglect, a defect of volition, which is the mnemonic counterpart of the volitional neglect of directional hypokinesia, which animals with this lesion also exhibit. The DA lesion was unilateral (for welfare reasons) so the information to be retrieved had to be confined to that hemisphere by the use of an IT ablation in the other hemisphere. Unilateral DA lesion compromises the competence of ipsilateral fronto-striatal interactions and our results parallel those found in monkeys with crossed IT x frontal lesions that are impaired on complex tasks requiring effortful implementation of a cognitive strategy but are not impaired on discrimination learning. Parkinsonian patients with sub-total but bilateral DA loss may lack 'top-down' conative mechanisms as well as 'top-down' movement initiation mechanisms. They may fail to initiate retrieval strategies, although they may not exhibit retrograde amnesia under test conditions that provoke retrieval. Failure to self-initiate retrieval of relevant knowledge may contribute to the paucity of cognitive style and loss of executive skills exhibited by some patients with Parkinson's disease.     

Visual agnosia and Klüver-Bucy syndrome in marmosets (Callithrix jacchus) following ablation of inferotemporal cortex, with additional mnemonic effects of immunotoxic lesions of cholinergic projections to medial temporal areas

Inferotemporal ablations in the New World monkey, the common marmoset (Callithrix jacchus), produced a persistent impairment on visual discrimination learning and a florid, but transient, Klüver-Bucy syndrome. Monkeys with these ablations were impaired on acquisition of object discriminations to a high criterion and on concurrent discrimination learning, to a single high criterion across all trials. Neither the control monkeys nor the monkeys with inferotemporal ablations found acquisition more difficult when the component discriminations of a set were presented concurrently compared to consecutively, although the monkeys with inferotemporal ablations found acquisition under both these conditions somewhat more difficult than did control monkeys. This suggests that the severe impairment caused by inferotemporal ablations on concurrent learning measured across all trials is due to the need for sustained performance across a concurrent set rather than to the extra mnemonic demands of concurrent presentation. When immunotoxic lesions of the cholinergic projection to the hippocampal formation were added to the inferotemporal ablations, a further impairment on retention, and a differential impairment on concurrent, compared to consecutive, learning was observed. Previous studies have shown that lesions of the cholinergic projection to the hippocampus alone, or excitotoxic hippocampal lesions, do not affect simple visual discrimination learning. It is suggested that large inferotemporal ablations in monkeys produce a visual agnosia which causes severe 'psychic blindness' in the first instance, and a persistent impairment on visual discrimination learning. The hippocampus makes a contribution, which may be mnemonic, to discrimination performance after inferotemporal ablations.     

Visual agnosia and Klüver–Bucy syndrome in marmosets (Callithrix jacchus) following ablation of inferotemporal cortex, with additional mnemonic effects of immunotoxic lesions of cholinergic projections to medial temporal areas

Inferotemporal ablations in the New World monkey, the common marmoset (Callithrix jacchus), produced a persistent impairment on visual discrimination learning and a florid, but transient, Klüver–Bucy syndrome. Monkeys with these ablations were impaired on acquisition of object discriminations to a high criterion and on concurrent discrimination learning, to a single high criterion across all trials. Neither the control monkeys nor the monkeys with inferotemporal ablations found acquisition more difficult when the component discriminations of a set were presented concurrently compared to consecutively, although the monkeys with inferotemporal ablations found acquisition under both these conditions somewhat more difficult than did control monkeys. This suggests that the severe impairment caused by inferotemporal ablations on concurrent learning measured across all trials is due to the need for sustained performance across a concurrent set rather than to the extra mnemonic demands of concurrent presentation. When immunotoxic lesions of the cholinergic projection to the hippocampal formation were added to the inferotemporal ablations, a further impairment on retention, and a differential impairment on concurrent, compared to consecutive, learning was observed. Previous studies have shown that lesions of the cholinergic projection to the hippocampus alone, or excitotoxic hippocampal lesions, do not affect simple visual discrimination learning. It is suggested that large inferotemporal ablations in monkeys produce a visual agnosia which causes severe ‘psychic blindness’ in the first instance, and a persistent impairment on visual discrimination learning. The hippocampus makes a contribution, which may be mnemonic, to discrimination performance after inferotemporal ablations.     

Learning impairments in monkeys with combined but not separate excitotoxic lesions of the anterior and mediodorsal thalamic nuclei

Clinical studies in humans and experiments in macaques suggest that damage to the anterior and the mediodorsal thalamus can induce a moderate amnesia, but a more dense impairment may result from substantial damage within the temporal lobes or their subcortical connections. Lesions of the anterior thalamus in macaques produce impairments which resemble those seen after lesions of the fornix–mamillary pathway, which carries projections from the hippocampus to the anterior thalamus, while lesions of the mediodorsal thalamus, which receives inputs from frontal and temporal cortex, produce moderate impairments on a wider range of memory tasks. In the present study, we have made bilateral excitotoxic lesions of either the anterior or the mediodorsal thalamus, or both, in marmoset monkeys. Monkeys with lesions of both thalamic nuclei were severely impaired on retention and new learning of examples of the visuospatial conditional task, a task which is specifically impaired by lesions of the fornix or hippocampus. They were not impaired on performance of a visuovisual conditional task on which monkeys with hippocampal lesions are impaired, nor were they impaired on any visual discrimination task, including the concurrent discrimination task on which monkeys with temporal neocortical ablations are impaired. Monkeys with separate lesions of either the anterior or the mediodorsal thalamus were not impaired on any of these tasks. These results suggest that the mediodorsal thalamus and the anterior thalamus are both involved in processing the output of the hippocampal–fornix–thalamic circuit. Dense amnesia may result from damage to circuits additional to the temporal lobe efferents to either the anterior or the mediodorsal nuclei.     

Severe learning impairment caused by combined immunotoxic lesion of the cholinergic projections to the cortex and hippocampus in monkeys

Monkeys with immunotoxic lesions of both the basal nucleus of Meynert and the vertical limb of the diagonal band of Broca (NBM+VDB) lost cholinergic innervation throughout the cortex and hippocampus. They were impaired at learning discriminations between objects differing in either few, or many, attributes and at learning visuospatial conditional discriminations. Monkeys with immunotoxic lesions of the NBM lost cholinergic innervation of the neocortex only. Initially, they were unable to learn a simple visual discrimination where the stimuli differed in a limited number of attributes but they were unimpaired at learning discriminations between objects that differed in more attributes. They were mildly impaired at learning a visuospatial conditional task. The impairment exhibited by monkeys with lesions of the NBM alone ameliorated with time but that following NBM+VDB lesions did not. Previous experiments have shown that monkeys with immunotoxic lesions of the VDB alone are impaired at learning visuospatial conditional discriminations but are unimpaired at learning simple visual discriminations. When monkeys with NBM lesions were given excitotoxic lesions of the CA1 field of the hippocampus the learning impairment on discriminations between objects which differed in few attributes was reinstated. Pretreatment with a cholinergic agonist improved learning ability on visual discrimination learning in all monkeys but this improvement was significantly greater in monkeys with lesions of the NBM. On conditional discrimination learning, which is particularly sensitive to hippocampal damage, pilocarpine produced a significant improvement in monkeys with NBM+VDB lesions (where the hippocampal dysfunction was cholinergic) but not in monkeys with NBM+CA1 lesions (where the hippocampal damage was structural).     

Severe tactual as well as visual memory deficits follow combined removal of the amygdala and hippocampus in monkeys

To determine whether medial temporal limbic structures are essential for memory in more than one modality, we trained monkeys preoperatively on both visual and tactual versions of a sensory memory task and then retested them after they had been given bilateral ablations of either the amygdaloid complex, the hippocampal formation, or both. Monkeys with the combined ablations were severely impaired in both modalities. By contrast, the amygdalectomized monkeys were only moderately impaired in the two modalities, while the hippocampectomized monkeys were impaired in neither. Further examination revealed that the source of the impairment in the monkeys with amygdalectomy alone, unlike that in the animals with combined lesions, was the small size of the pool from which the test objects were drawn. The latter result suggests that, whereas the sensory memory impairment following the combined lesions is basically a recognition loss, the more selective impairment following amygdalectomy alone reflects special difficulty in determining whether a recognized object was presented recently. By demonstrating that the profound sensory memory impairment that follows combined ablation of the amygdala and hippocampus extends beyond a single modality, the present results strengthen the proposals that these two structures are important for sensory memory in all modalities and the multimodal or global amnesia observed in patients with medial temporal lobe damage is likewise due to combined amygdaloid and hippocampal lesions.     

Further analysis of the effects of immunotoxic lesions of the basal nucleus of Meynert reveals substantial impairment on visual discrimination learning in monkeys

In this paper we undertake a combined analysis of several studies in which marmoset monkeys received immunotoxic lesions of the cortical cholinergic projections from the basal nucleus of Meynert (NBM) bilaterally and/or in combination with immunotoxic lesions of other parts of the cholinergic system or ablations of the target inferotemporal neocortical area. Analysis of the mean learning scores across all visual discriminations learning tasks for each lesion combination revealed highly significant impairments where the NBM was lesioned bilaterally or where an NBM lesion in one hemisphere was crossed with an inferotemporal cortical ablation in the other hemisphere. This demonstrates that the cholinergic projection from the NBM to the major target area of neocortex involved in visual discrimination learning, i.e. the inferotemporal cortex, makes an important contribution to the perceptuo-mnemonic processes necessary for this type of learning. A new study demonstrates a significant effect of a subtotal bilateral cholinergic lesion confined to the NBM on a concurrent object-reward association task using black objects which is perceptually and mnemonically demanding. These results do not preclude the possibility that cholinergic projections from the NBM to other parts of the neocortex make a contribution to other cortical functions which are not mnemonic. It is well established that lesions of the cholinergic projection from the diagonal band of Broca disrupts the mnemonic functions of the hippocampus. The results described here suggest that degeneration of the cholinergic projections in Alzheimer's disease and other dementias will contribute to the loss of those mnemonic functions which are dependent on the neocortex.     

Hippocampal lesions impair performance on a conditional delayed matching and non-matching to position task in the rat

The hippocampus is thought to be involved in a range of cognitive processes, from the ability to acquire new memories, to the ability to learn about spatial relationships. Humans and monkeys with damage to the hippocampus are typically impaired on delayed matching to sample tasks, of which the operant delayed matching to position task (DMTP) is a rat analogue. The reported effects of hippocampal damage on DMTP vary, ranging from delay-dependent deficits to no deficit whatsoever. The present study investigates a novel memory task; the conditional delayed matching/non-matching to position task (CDM/NMTP) in the Skinner box. CDM/NMTP uses the presence of specific stimulus cues to signify whether a particular trial is matching or non-matching in nature. Thus, it incorporates both the task contingencies within one session, and supplements the requirement for remembering the side of the lever in the sample phase with attending to the stimulus and remembering the conditional discrimination for the rule. Rats were trained preoperatively and the effects of bilateral excitotoxic lesions of the hippocampus were examined on postoperative retention of the task. Rats with lesions of the hippocampus incurred a significant impairment on the task that was manifest at all delays intervals. Despite a bias towards matching during training, trials of either type were performed with equivalent accuracy and neither rule was affected differentially by the lesion. This task may prove useful in determining the cognitive roles of a range of brain areas.     

Spatial and object reversal learning in monkeys with partial temporal lobe ablations

Effects of frontal and combined medial temporal, or amygdala and hippocampal lesions separately, were compared on delayed alternation, delayed response, spatial and object reversals and non-spatial delayed alternation. Failure on spatial delayed alternation but not delayed response characterized all monkeys with temporal lobe lesions. Frontal, medial temporal and amygdala lesions resulted in varying degrees of impairment on spatial and object reversals, while hippocampal lesion produced a deficit on spatial but not object reversals. All monkeys with temporal lobe lesions achieved normal learning scores on nonspatial delayed alternation, but hippocampal monkeys were most efficient. The effects of medial temporal lesions are discussed in terms of the relative contributions of the amygdala and hippocampal ablations to the total syndrome.     

Dissociation of the effects of inferior temporal and limbic lesions on object discrimination learning with 24-h intertrial intervals

Monkeys with bilateral ablations of the inferior temporal cortical area TE were trained on a visual discrimination task thought to measure non-cognitive habit formation. The task consisted of 20 object discriminations presented concurrently, but at the rate of only one trial on each per day; successive trials on a given discrimination were thus separated by 24-h intertrial intervals. Performance on this task by the animals with TE lesions was compared to that of both normal control monkeys and monkeys that had sustained bilateral removals of the amygdala and hippocampus. In contrast to the latter animals, which learned the 24-h intertrial interval task about as quickly as the normal controls, monkeys with area TE removals were markedly impaired. Taken together with earlier findings demonstrating that ablation of area TE impairs visual recognition memory, the present results suggest that area TE contributes not only, like limbic structures, to a cognitive memory system, but also, unlike limbic structures, to a non-cognitive habit system. Evidence is reviewed suggesting that this latter system may involve a corticostriatal circuit.     

Topographical memory impairments after unilateral lesions of the anterior thalamus and contralateral inferotemporal cortex

Monkeys with crossed unilateral excitotoxic lesions of the anterior thalamus and unilateral inferotemporal cortex ablation were severely impaired at learning two tasks which required the integration of information about the appearance of objects and their positions in space. The lesioned monkeys were also impaired at learning a spatial task and a task which required the integration of information about the appearance of objects and the background on which the objects were situated. Monkeys with only one of the unilateral lesions were not impaired and previous work has shown that monkeys with bilateral lesions of the anterior thalamus were not impaired on these tasks. These results indicate that the whole of the inferotemporal cortex-anterior thalamic circuit, which passes via the hippocampus, fornix, mamillary bodies and mamillothalamic tract, is essential for the topographical analysis of information about specific objects in different positions in space. Together with previous work, the results show that a unilateral lesion may affect cognition in the presence of other brain damage when an equivalent bilateral lesion alone does not. The tasks required the slow acquisition of information into long term memory and therefore assessed semantic knowledge although other research has shown impairment on topographical processing within working or episodic memory following lesions of the hippocampal-diencephalic circuit. It is argued that the hippocampal-diencephalic circuit does not have a role in a specific form of memory such as episodic memory but rather is involved in topographical analysis of the environment in perception and across all types of declarative memory.     

Lesions of perirhinal and parahippocampal cortex that spare the amygdala and hippocampal formation produce severe memory impairment

In monkeys, bilateral damage to the medial temporal region produces severe memory impairment. This lesion, which includes the hippocampal formation, amygdala, and adjacent cortex, including the parahippocampal gyrus (the H+A+ lesion), appears to constitute an animal model of human medial temporal lobe amnesia. Reexamination of histological material from previously studied monkeys with H+A+ lesions indicated that the perirhinal cortex had also sustained significant damage. Furthermore, recent neuroanatomical studies show that the perirhinal cortex and the closely associated parahippocampal cortex provide the major source of cortical input to the hippocampal formation. Based on these 2 findings, we evaluated the severity of memory impairment in a group of monkeys that received bilateral lesions limited to the perirhinal cortex and parahippocampal gyrus (the PRPH lesion). The performance of the PRPH group was compared with that of monkeys with H+A+ lesions, who had been studied previously, and with a group of normal monkeys. Monkeys with PRPH lesions were severely impaired on 3 amnesia-sensitive tasks: delayed nonmatching to sample, object retention, and 8-pair concurrent discrimination. On pattern discrimination, a task analogous to ones that amnesic patients perform well, monkeys in the PRPH group performed normally. Overall, monkeys with PRPH lesions were as impaired or more impaired than the comparison group of monkeys with H+A+ lesions. These and other recent findings (Zola-Morgan et al., 1989b) suggest that the severe memory impairment in monkeys and humans associated with bilateral medial temporal lesions results from damage to the hippocampal formation and adjacent, anatomically related cortex, not from conjoint hippocampus-amygdala damage.     

No effect of hippocampal lesions on perirhinal cortex-dependent feature-ambiguous visual discriminations

Previous studies have shown that perirhinal cortex lesions in monkeys impair visual discriminations with a high degree of "feature ambiguity," a property of visual discriminations that can emerge when features are a part of both rewarded and unrewarded stimuli. The effects of damage to the hippocampus on these perirhinal-dependent feature-ambiguous tasks are, however, unknown. Prominent theories of medial temporal lobe function predict similar effects of perirhinal cortex and hippocampal lesions on cognitive tasks. In contrast, our hypothesis is that perirhinal cortex, and not the hippocampus, is important for nonspatial complex feature-ambiguous discriminations. We sought to distinguish between these competing theories in a straightforward way, by testing rhesus monkeys with hippocampal lesions on the same feature-ambiguous tasks shown previously to depend on perirhinal cortex. It was found that hippocampal lesions had no effects on any of these tasks. The findings support the perceptual-mnemonic/feature conjunction model of perirhinal cortex function, and provide further evidence for heterogeneity of function within the putative medial temporal lobe memory system.     

Amygdalar interaction with the mediodorsal nucleus of the thalamus and the ventromedial prefrontal cortex in stimulus-reward associative learning in the monkey

Cynomolgus monkeys (Macaca fascicularis) were assessed for their ability to associate visual stimuli with food reward. They learned a series of new 2-choice visual discriminations between colored patterns displayed on a monitor screen. The feedback for correct choice was the delivery of food. In order to promote associative learning between the visual stimuli and the incentive value of the food reward, reward delivery was not accompanied by any distinctive visual feedback on the display screen. The rate of learning new problems was assessed before and after surgery in a total of 16 monkeys. Three groups of 3 monkeys received bilaterally symmetrical ablations in either the amygdala, the mediodorsal nucleus of the thalamus, or the ventromedial prefrontal cortex. All these groups showed a severe postoperative learning impairment. Seven other animals were given a unilateral ablation in 1 of those 3 structures and a second unilateral ablation, in each case contralateral to and different from the first, in order to produce 2 groups in which a putative amygdalo-thalamo-prefrontal pathway had been disconnected by crossed unilateral lesions. One disconnection group had lesions in the amygdala and ventromedial prefrontal cortex; the other had lesions in the amygdala and the mediodorsal nucleus of the thalamus. The disconnection groups showed a significant impairment, but the effect of the disconnection surgeries was significantly milder than the effect of any of the 3 bilaterally symmetrical lesions. Therefore, symmetrical bilateral lesions in either the amygdala, the mediodorsal nucleus, or the ventromedial prefrontal cortex produce similar impairments in the present task, implying that these structures are functionally related to each other; but the relatively mild effect of disconnecting these structures from each other argues against the hypothesis that they are serial stages in a single, tightly linked functional pathway.     

Neurotoxic lesions of ventrolateral prefrontal cortex impair object-in-place scene memory

Disconnection of the frontal lobe from the inferotemporal cortex produces deficits in a number of cognitive tasks that require the application of memory-dependent rules to visual stimuli. The specific regions of frontal cortex that interact with the temporal lobe in performance of these tasks remain undefined. One capacity that is impaired by frontal-temporal disconnection is rapid learning of new object-in-place scene problems, in which visual discriminations between two small typographic characters are learned in the context of different visually complex scenes. In the present study, we examined whether neurotoxic lesions of ventrolateral prefrontal cortex in one hemisphere, combined with ablation of inferior temporal cortex in the contralateral hemisphere, would impair learning of new object-in-place scene problems. Male macaque monkeys learned 10 or 20 new object-in-place problems in each daily test session. Unilateral neurotoxic lesions of ventrolateral prefrontal cortex produced by multiple injections of a mixture of ibotenate and N-methyl-D-aspartate did not affect performance. However, when disconnection from inferotemporal cortex was completed by ablating this region contralateral to the neurotoxic prefrontal lesion, new learning was substantially impaired. Sham disconnection (injecting saline instead of neurotoxin contralateral to the inferotemporal lesion) did not affect performance. These findings support two conclusions: first, that the ventrolateral prefrontal cortex is a critical area within the frontal lobe for scene memory; and second, the effects of ablations of prefrontal cortex can be confidently attributed to the loss of cell bodies within the prefrontal cortex rather than to interruption of fibres of passage through the lesioned area.     

Disconnecting hippocampal projections to the anterior thalamus produces deficits on tests of spatial memory in rats

A disconnection procedure was used to test whether projections from the hippocampus to the anterior thalamic nuclei (AT), via the fimbria-fornix (FX), form functional components of a spatial memory system. The behavioural effects of combined unilateral lesions in the AT and FX were compared when they were either in contralateral hemispheres (AT-FX Contra) or the same hemisphere (AT-FX Ipsi). Other groups received bilateral FX lesions and Sham surgeries. Expt 1 demonstrated that none of these lesions affected performance of an object recognition task, while performance of an object location task, which tests the subjects' preference for an object that has changed location, was impaired in the AT-FX Contra and FX groups. In a T-maze alternation task, however, the FX group was severely impaired while both the AT-FX Ipsi and AT-FX Contra lesion groups showed only a mild impairment. In order to test whether spared crossed projections might support spatial performance in the AT-FX Contra group we then examined the effects of a combined AT-FX Contra lesion coupled with transection of the hippocampal commissure. This combination of lesions produced a severe disruption in spatial memory performance in the water maze, radial arm maze and T-maze, which was significantly greater than that produced by ipsilateral and contralateral AT-FX lesions alone. These results support the notion that disconnection of the AT from their hippocampal inputs produces impairments on a range of spatial memory tasks, but indicate that there are an array of different routes that can subserve this function.     

Enduring memory impairment in monkeys after ischemic damage to the hippocampus.

Patient RB became amnesic following an episode of global ischemia that resulted in a bilateral lesion of the CA1 field of the hippocampus. This finding suggested that damage restricted to the hippocampus is sufficient to produce clinically significant memory impairment. To evaluate further the effect of ischemic brain damage on memory, we have developed an animal model of cerebral ischemia in the monkey. Monkeys were subjected to 15 min of reversible ischemia, using a noninvasive technique involving carotid occlusion and pharmacologically induced hypotension. These monkeys sustained significant loss of pyramidal cells in the CA1 and CA2 fields of the hippocampus, as well as loss of somatostatin-immunoreactive cells in the hilar region of the dentate gyrus. Cell loss occurred bilaterally throughout the rostrocaudal extent of the hippocampus but was greater in the caudal portion. Except for patchy loss of cerebellar Purkinje cells, significant damage was not detected in areas outside the hippocampus, including adjacent cortical regions, that is, entorhinal, perirhinal, and parahippocampal cortex, and other regions that have been implicated in memory function. On behavioral tests, the ischemic monkeys exhibited significant and enduring memory impairment. On the delayed nonmatching to sample task, the ischemic monkeys were as impaired as monkeys with lesions of the hippocampal formation and adjacent parahippocampal cortex (the H+ lesion). On two other memory tasks, the ischemic monkeys were less impaired than monkeys with the H+ lesion. In neuropathological evaluations, it has always been difficult to rule out the possibility that significant areas of neuronal dysfunction have gone undetected. The finding that ischemic lesions produced overall less memory impairment than H+ lesions indicates that the ischemic monkeys (and by extension, patient RB) are unlikely to have widespread neuronal dysfunction affecting memory that was undetected by histological examination. These results provide additional evidence that the hippocampus is a focal site of pathological change in cerebral ischemia, and that damage limited to the hippocampus is sufficient to impair memory.     

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.     

The importance of the rat hippocampus for learning the structure of visual arrays

It has been assumed that the integrity of the rodent hippocampus is required for learning the spatial distribution of visual elements in an array. Formally assessing this assumption is, however, far from straightforward as standard tests are amenable to alternative strategies. In order to provide a stringent test of this ability rats were trained on three concurrent visual discriminations in a water tank in which the stimuli in each pair of discriminations contained exactly the same elements but they differed in their spatial arrangement e.g. A|B vs. its mirror image B/A. Such 'structural' discriminations are a specific subtype of 'configural' or 'nonlinear' tasks. Following acquisition half of the rats received hippocampal lesions and all rats were retrained on the structural discriminations. Hippocampal lesions impaired the ability to relearn these 'structural' discriminations. In contrast, two other groups of rats with similar hippocampal lesions showed no impairment on relearning two non-structural, configural discriminations: transverse patterning and biconditional learning. All three tasks used the same apparatus, the same stimulus elements, and similar training regimes. Superior performance by the rats with hippocampal lesions during a generalization decrement probe showed that hippocampal lesions had diminished sensitivity to 'structural' features on the biconditional task. While the rat hippocampus need not be required for all configural learning, it is important for the special case when the spatial arrangements of the elements are critical. This ability may be a prerequisite for the creation of mental snapshots, which underlie episodic memory.