Seizure activity in the rat hippocampus, perirhinal and prefrontal cortex associated with transient global cerebral ischemia.

Epileptiform EEG activity associated with ischemia can contribute to early damage of hippocampal neurons, and seizure activity may also lead to dysfunction in extrahippocampal regions. In this study, seizure activity associated with the four-vessel occlusion model of cerebral ischemia was monitored using chronically implanted electrodes in the CA1/subicular region, the perirhinal cortex, and the prefrontal cortex of the rat. Background EEG amplitude was reduced in all recording sites during occlusion, but spiking and bursting activity was also observed. Seizure activity occurred in most animals during the first several hours of reperfusion, but was not observed on subsequent days. Epileptiform spikes and bursts were often synchronous between two or three recording sites, and spikes in the CA1 region also often occurred just prior to spikes in other sites. These results demonstrate that the four-vessel occlusion model can lead to patterns of seizure activity in the hippocampus, prefrontal and perirhinal cortices.

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.

Anterograde and retrograde memory for object discriminations and places in rats with perirhinal cortex lesions.

Three experiments examined the effects of perirhinal cortex lesions on rats' retrograde and anterograde memory for object-discriminations and water-maze place-memory problems. In Experiment 1, rats learned two object-discriminations - the first was learned 2 weeks before surgery and the second 24 h before surgery. Rats with perirhinal cortex lesions displayed mildly impaired retention of both object discriminations, with no evidence of a temporal gradient. They also learned a new discrimination at a normal rate, but were impaired on a retention test 24 h later. In Experiment 2, rats learned two water-maze place problems, conducted in different rooms - the first was learned 4 weeks before surgery and the second during the week immediately before surgery. Rats with perirhinal cortex lesions displayed deficits on the early retention trials of both place problems, but they quickly relearned both problems. In Experiment 3, rats with perirhinal cortex lesions learned a new place problem at a normal rate and performed as well as control rats on a retention test 3 weeks later. Although some of the results are consistent with the conclusion that perirhinal damage disrupts storage or retrieval of place information acquired before surgery, additional considerations suggest instead a role for perirhinal cortex in the representation of nonspatial information that makes a useful but nonessential contribution to water-maze performance.

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.

Impaired allocentric spatial working memory and intact retrograde memory after thalamic damage caused by thiamine deficiency in rats.

Rats were tested on an allocentric-spatial working-memory task--delayed matching-to-place (DMTP) in a water maze--before and after either pyrithiamine-induced thiamine deficiency (PTD) or electrolytic lesions of the lateral internal medullary laminae (IML), an area damaged by PTD. DMTP trials consisted of paired swims, with the escape platform in a new location on each trial. PTD rats were impaired at retention delays of 300 s, but not at delays of 4 or 60 s. Rats with IML lesions performed normally at all delays. Both groups displayed normal retention of object-discrimination problems that they had learned at different intervals before treatment (5 weeks, 3 weeks, and 1 week). The results suggest that PTD causes delay-dependent deficits of allocentric spatial working memory and that damage outside the IML is probably responsible. Neither PTD-induced diencephalic damage nor restricted IML lesions appear to produce a global retrograde amnesia.

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.

Object-recognition and spatial learning and memory in rats prenatally exposed to ethanol.

Prenatal ethanol exposure can produce cognitive and behavioral impairments. In the present study, rats from prenatal ethanol (E), pair-fed (PF), and ad libitum-fed control (C) treatment conditions were tested on the object-recognition delayed-nonmatching-to-sample (DNMS) task with nonrecurring items and on the spatial-navigation Morris water maze task. In Experiment 1, there were no significant differences among groups in object-recognition learning and memory, distractibility, or response perseveration on the DNMS task. In Experiment 2, the same rats were tested in the water maze; E rats took significantly longer to learn the task than did the PF or C rats. These data suggest that the mechanisms underlying spatial cognitive abilities are more vulnerable to the teratogenic effects of prenatal ethanol exposure than those underlying object-recognition abilities.

Ischemia-induced object-recognition deficits in rats are attenuated by hippocampal ablation before or soon after ischemia.

The literature on the role of the hippocampus in object-recognition contains a paradox: Transient forebrain ischemia (ISC) produces hippocampal damage and severe deficits on the delayed nonmatching-to-sample (DNMS) task, yet hippocampal ablation (ABL) produces milder deficits. Experiment 1 confirmed that pretrained rats display severe DNMS deficits following ISC, but not ABL. Ischemia produced loss of CA1 neurons, but no obvious extrahippocampal damage. In Experiments 2 and 3, ISC rats from Experiment 1 received ABL, and ABL rats received ISC; neither treatment affected DNMS performance. In Experiment 4, rats that received ISC followed 1 hr later by ABL displayed only mild deficits. It is hypothesized that ISC-induced DNMS deficits are due to extrahippocampal damage produced by pathogenic processes that involve the hippocampus.

Pyrithiamine-induced thiamine deficiency impairs object recognition in rats.

Pyrithiamine-induced thiamine deficiency (PTD) in rats is used to model the etiology, diencephalic neuropathology, and memory deficits of Korsakoff's amnesia. We assessed the performance of rats exposed to PTD on a test of object recognition--nonrecurring-items delayed nonmatching-to-sample (DNMS). PTD produced thalamic lesions similar to those of Korsakoff's amnesics and similar to those previously observed in PTD rats. PTD rats required more trials to master DNMS at a 4-s retention delay than did controls, and after they had done so, they performed more poorly than controls at delays of 15, 30, 60, and 120 s. DNMS deficits were also observed in PTD rats that received training prior to PTD treatment. These findings support the validity of the PTD rat model of Korsakoff's disease by demonstrating that PTD rats display object-recognition deficits that are similar to those reported in Korsakoff amnesics.

Rat (Rattus norvegicus) defensive behavior in total darkness: risk-assessment function of defensive burying.

Although rats (Rattus norvegicus) spend much of their lives in the darkness of burrows, defensive behavior in the dark has rarely been studied. We compared rats' reactions to aversive stimuli in dark and lighted 2-alley, burrowlike environments. Experiment 1 assessed reactions to an unsignaled airblast; Experiment 2 assessed neophobic reactions to an unfamiliar steel ball. Half of the rats were tested in light and half, in total darkness. In both experiments rats directed defensive burying and stretched approach toward the aversive stimulus. Darkness increased airblast-induced burying behavior but not burying behavior toward the unfamiliar object; it had no effect on stretched-approach behavior in either experiment. Because the location and nature of the aversive stimulus was ambiguous in Experiment 1 but not in Experiment 2, these results support the hypothesis that risk assessment is one function of defensive-burying behavior.

Rhinal cortex lesions and object recognition in rats.

Rats with bilateral lesions of lateral entorhinal cortex and perirhinal cortex were tested on a nonrecurring-items delayed nonmatching-to-sample (DNMS) task resembling the one that is commonly used to study object recognition in monkeys. The rats were tested at retention delays of 4 s, 15 s, 60 s, 120 s, and 600 s before and after surgery. After surgery, they displayed a delay-dependent deficit: They performed normally at the 4-s delay but were impaired at delays of 15 s 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 and amygdala cause only mild DNMS deficits in rats unless there is also damage to rhinal cortex (D.G. Mumby, E.R. Wood, & J.P.J. Pinel, 1992). These findings add to accumulating evidence that the rhinal cortex, but not the amygdala, plays a critical role in object recognition.

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.

The limbic system and food-anticipatory circadian rhythms in the rat: ablation and dopamine blocking studies.

Rats behaviorally anticipate a fixed, daily opportunity to feed by entrainment of circadian oscillators that are physically separate from the light-entrainable circadian pacemaker that has been localized to the suprachiasmatic nucleus. Neural substrates mediating food-entrained rhythms are unknown. A variety of anatomical and functional observations suggest possible involvement of the limbic system and its dopaminergic component in the regulation of these rhythms. To test this hypothesis, the activity rhythms of rats bearing large, combined ablations of the hippocampus and amygdala or nucleus accumbens and medical forebrain anterior to the thalamus were examined under ad-lib feeding, 2 h daily feeding, and total food deprivation conditions. Some hippocampal-ablated rats showed alterations of free-running rhythms under ad-lib feeding, but none of the ablations impaired the rats' ability to anticipate daily feeding, or 'remember' the phase of feeding time during subsequent food deprivation. Additional groups of intact rats were treated with the dopamine antagonist haloperidol (0.3 mg/kg or 2.0 mg/kg) 30 min prior to daily feeding, but this also did not prevent the emergence of food-entrained rhythms. The limbic and dopamine systems do not appear to play a necessary role in the generation or entrainment of food-anticipatory circadian rhythms.