Visual discrimination learning and transfer in rats with hippocampal lesions

Two experiments were performed on rats with hippocampal brain damage and on a control group with neocortical lesions. In the first experiment the hippocampal group learned a difficult visual discrimination as promptly as the controls, and neither group was subsequently impaired by adding relevant or irrelevant background cues to the original stimuli. In the second experiment the animals learned a simultaneous visual discrimination in which the stimuli differed in both brightness and orientation. The hippocampal group was impaired relative to the controls on acquisition, and showed poorer transfer to stimuli differing only in brightness or orientation. The results are incompatible with the hypothesis which attempts to explain the effects of hippocampal damage by a widespread reduction in sensory gating, but they are consistent with a more restricted version of the same hypothesis.     

Role of interference in retention by rats with hippocampal lesions.

Involvement of the hippocampus in memory was studied in the rat by employing a retention task with and without interpolated activity. Rats with extensive damage to hippocampus were able to relearn a preoperatively acquired single-alternation task with savings and to perform the single alternation with relatively long delays at a level similar to that of control subjects. However, hippocampals were more affected than normals by an interpolated activity that interferes with retention. The finding of normal retention combined with increased susceptibility to interference supports the view that the memory impairment in subjects with damage to hippocampus may be due to an excess of interference among stored information.     

Revisiting places passed: sensitization of exploratory activity in rats with hippocampal lesions

We examined the involvement of the hippocampus in short-term changes in exploratory behaviour in an open field (Experiment 1) and experimental contexts (Experiment 2). In Experiment 1, rats with excitotoxic lesions of the hippocampus were more likely to revisit recently visited zones within the open field than were control rats. Similarly, in Experiment 2 rats with hippocampal lesions showed greater exploration of a context that they had recently explored than a context that they had less recently explored. This short-term sensitization effect was not evident in control rats. These findings are consistent with the suggestion that the recent presentation of a stimulus has two opposing effects on behaviour, sensitization, and habituation, and that hippocampal lesions disrupt the short-term process responsible for habituation, but not that responsible for sensitization.     

Revisiting places passed: Sensitization of exploratory activity in rats with hippocampal lesions

We examined the involvement of the hippocampus in short-term changes in exploratory behaviour in an open field (Experiment 1) and experimental contexts (Experiment 2). In Experiment 1, rats with excitotoxic lesions of the hippocampus were more likely to revisit recently visited zones within the open field than were control rats. Similarly, in Experiment 2 rats with hippocampal lesions showed greater exploration of a context that they had recently explored than a context that they had less recently explored. This short-term sensitization effect was not evident in control rats. These findings are consistent with the suggestion that the recent presentation of a stimulus has two opposing effects on behaviour, sensitization, and habituation, and that hippocampal lesions disrupt the short-term process responsible for habituation, but not that responsible for sensitization.     

The effects of aging and dorsal hippocampal lesions: performance on spatial and nonspatial comparable versions of the water maze

Aged intact and young hippocampal-lesioned rats show similar deficits on the spatial water maze. However, this does not necessitate that the source of these deficits in the aged animals is due to hippocampal damage. These water maze deficits may arise from other aging factors such as changes in thermoregulation, muscle fatigue, swim ability, and response to stress. Consequently, it is imperative to examine the performance of aged rats on a comparable nonhippocampal version of this task. Past attempts to develop a hippocampus-independent version of the water maze were confounded because these tasks were easier (i.e., the rats spent much less time swimming in the water) than the spatial versions of the task. The current study examined performance on a hippocampus-independent task comparable in difficulty to the spatial water one. Middle-aged (16-m) and old (25-m) male F344 rats were given sham or dorsal hippocampus lesions and tested on both a spatial and a nonspatial water maze. The middle-aged rats with hippocampal lesions were impaired on the spatial task but not on the nonspatial task. Conversely, aged animals showed a similar impairment on both types of water maze tasks. Additionally, hippocampal lesions exacerbated the age-related impairment on both tasks. These findings indicate that caution must be used when interpreting the results of water maze tasks for aged animals.     

The effects of clozapine on delayed spatial alternation deficits in rats with hippocampal damage

Clozapine is an atypical antipsychotic drug that has been shown to improve spatial memory in some animal models; however its efficacy in reversing spatial memory impairment in rats with hippocampal lesions is unknown. To address this issue, we tested the effects of clozapine on delayed spatial alternation deficits in rats with hippocampal damage in three separate experiments. In each experiment, adult male rats received sham surgery or direct stereotaxic infusions of the excitotoxin, NMDA, into the hippocampus. In the first study, seven days after surgery, the sham control animals received daily saline injections while the lesioned animals were split into two groups that received daily saline or clozapine (2.0 mg/kg, sc) injections. During the fifth week of injections, all animals were tested in a food-motivated delayed spatial alternation task. Saline-treated rats with excitotoxic hippocampal damage displayed significant deficits in delayed spatial alternation. Daily clozapine injections completely reversed this deficit. In a second experiment, it was found that clozapine treatment limited to the testing days only did not improve alternation performance in lesioned rats. Finally, in a third experiment, chronic clozapine treatment did not improve alternation performance in lesioned rats that were pre-trained in the alternation task prior to surgery. These results suggest that chronic, but not acute, clozapine treatment enables rats with hippocampal damage to develop new spatial learning, but can not rescue old spatial learning established prior to damage. These results may have implications for the treatment of cognitive deficits caused by hippocampal dysfunction in disorders such as schizophrenia, Alzheimer's disease, and others.     

Dissociation of data-based and expectancy-based memory following hippocampal lesions in rats

Sham-operated and nonoperated animals or animals with hippocampal lesions were presented with sets of trials to test both expectancy-based and data-based memory within the same task. During the study phase of each trial the animals were presented with a constant sequence of five arms on an eight-arm radial maze followed by a test phase in which a recognition test requiring a win-stay rule was used. Expectancy-based memory was measured during the study phase of the trials as a pattern of correct or incorrect orienting responses in anticipation of the ensuing doors in the constant sequence. Both groups of animals acquired correct orienting responses at the same rate, emitted the same pattern of correct orienting responses, and made the same number and pattern of intralist and extralist intrusion errors. Data-based memory was measured during the test phase of the trial as correct recognition test performance. During the test phase the animals with hippocampal lesions were impaired relative to controls on both immediate and 24-h recognition tests. These results suggest that the hippocampus might mediate only data-based, but not expectancy-based, memory and imply a possible dissociation between expectancy-based and data-based memory systems.     

The effects of hippocampal lesions on learning, memory, and reward expectancies

The hippocampus appears to be critical for the formation of certain types of memories. Hippocampal-lesioned animals fail to exhibit some spatial, contextual, and relational associations. After aspiration lesions of the hippocampus and/or cortex, male rats were allowed to recover for three weeks before being trained on a matching-to-position task. The matching-to-position task was altered to influence the type of cognitive strategies a subject would use to solve the task. The main behavioral manipulation was the reinforcement contingency assignment: Use of a differential outcomes procedure (DOP) or a nondifferential outcomes procedure (NOP). The DOP involves correlating each to-be-remembered event with a distinct reward condition via Pavlovian trace conditioning, whereas the NOP results in random reward contingency. We found that hippocampal lesions did retard learning the matching rule, regardless of the reinforcement contingency assignment. However, when delay intervals were added to the task memory performance of subjects with hippocampal lesions was dramatically impaired--if subjects were not trained with the DOP. When subjects were trained with the DOP, the hippocampal lesion had a marginal effect on delayed memory performance. These findings demonstrate two important points regarding lesions of the hippocampus: (1) hippocampal lesions have a minimal effect on the on the ability of rats to use reward information to solve a delayed discrimination task; (2) rats with hippocampal lesions have the ability to learn about reward information using Pavlovian trace conditioning procedures.     

Preserved learning about allocentric cues but impaired flexible memory expression in rats with hippocampal lesions

Several studies have shown that slight modifications in the standard reference spatial memory procedure normally used for allocentric learning in the Morris water maze and the radial maze, can overcome the classic deficit in allocentric navigation typically observed in rats with hippocampal damage. In these special paradigms, however, there is only intramaze manipulation of a salient stimulus. The present study was designed to investigate whether extramaze manipulations produce a similar outcome. With this aim a four-arm plus-shaped maze and a reference spatial memory paradigm were used, in which the goal arm was marked in two ways: by a prominent extramaze cue (intermittent light), which maintained a constant relation with the goal, and by the extramaze constellation of stimuli around the maze. Experiment 1 showed that, unlike the standard version of the task, using this special training procedure hippocampally-damaged rats could learn a place response as quickly as control animals; importantly, one day after reaching criterion, lesioned and control subjects performed the task perfectly during a transfer test in which the salient extramaze stimulus used during the acquisition was removed. However, although acquisition deficit was overcomed in these lesioned animals, a profound deficit in retention was detected 15 days later. Experiment 2 suggests that although under our special paradigm hippocampal rats can learn a place response, spatial memory only can be expressed when the requisites of behavioral flexibility are minimal. These findings suggest that, under certain circumstances, extrahippocampal structures are sufficient for building a coherent allocentric representation of space; however, flexible memory expression is dependent, fundamentally, on hippocampal functioning.