Hippocampal-lesioned Rats Research Articles

Latent learning in hippocampal-lesioned rats

The ability of rats with lesions of the anterior hippocampus to demonstrate latent learning of a spatial maze was examined in a Hebb-Williams maze apparatus. Significant latent learning in both hippocampal-lesioned and control rats with unrewarded preexposure to the maze pattern was found on the initial trials. Unlike the control rats, however, the hippocampal-lesioned rats showed little further error reduction across the remaining test trials. The results are discussed in terms of O'Keefe and Nadel's model of the mammalian hippocampus as a “cognitive map.”

Hippocampal lesion effects on conditioned taste aversion and pituitary-adrenal activity in rats

A series of experiments examined the effects of hippocampal lesions on conditioned taste aversion (CTA) and pituitary-adrenal activity. Experiment 1 examined recovery from a conditioned taste aversion under conditions of free extinction. Hippocampal and unoperated rats recovered from the aversion at the same rate. Further, this experiment showed that the suppression in drinking in both groups produced by lithium chloride (LiCl) injection was a conditioned taste aversion (was dependent upon the contingent pairing of the taste stimulus with LiCl) and not enhanced neophobia. In Experiment 2 there were no behavioral effects of the lesion in a forced extinction CTA paradigm. In addition, hippocampal lesions failed to alter pituitary-adrenal responsiveness to LiCl. In the same experiment, pituitary-adrenal responsiveness of hippocampectomized rats, when re-exposed to the taste paired earlier with LiCl, was altered. Hippocampal lesions eliminated the elevation in corticosterone shown by unoperated control and neocortical-lesioned rats. The third experiment replicated this finding showing again that hippocampal-lesioned rats failed to show the forced extinction elevation in corticosterone when re-exposed to the aversive taste (Experiment 3). These data were integrated with other reports of behavioral and pituitary-adrenal alterations in hippocampal-lesioned rats.

Facilitation of discriminated rearing-avoidance in rats with hippocampal lesions.

Effects of bilateral hippocampal lesions were investigated in a newly developed discriminated rearing-avoidance task. A significant facilitation of avoidance conditioning was found in rats with hippocampal lesions. The over-all escape topography of the hippocampal-lesioned rats was mostly jumping whereas that of the controls was rearing. These findings suggest that the hippocampal lesion increases reactivity to shock.

Nerve growth factor applications fail to alter behavior of hippocampal-lesioned rats

Rats were given one-stage, bilateral hippocampal lesions. Some of these animals were also administered approximately 2400 BU of 7S Nerve Growth Factor at the time of the operation. Other animals were administered a saline solution. Applications were made directly to the lesioned brain tissue. All rats were tested on two spatial mazes on postoperative days 49 and 50. No behavioral differences were noted as a function of NGF application; all hippocampal-lesioned rats displayed impaired spatial maze acquisition. The effect of NGF on the development of lesion-induced anomalous noradrenergic innervaion was examined with a modified glyoxylic acid technique. It was not possible to discern a consistent difference in fluorescence as a function of NGF application.

Effect of hippocampal lesions on heart-rate during classical fear conditioning

Of 22 male albino rats, eight received bilateral lesions at three levels of the hippocampus, six received bilateral lesions of the amygdaloid complex and eight served as unoperated controls. Each rat received 30 fear conditioning trials in which shock was paired with a CS, either light or a tone. After every tenth trial there was a test trial in which heart-beats were recorded. The typical heart-rate response of controls was deceleration-acceleration while for hippocampal lesioned rats it was short latency acceleration. The results were interpreted in terms of two heart-rate theories.

Hippocampal lesions slow extinction of a conditioned taste aversion in rats

Rats were subjected to either a bilateral removal of the superior cervical ganglia or to a sham operation of the neck. In subsequent operations, these animals underwent either bilateral dorsal hippocampal lesions, bilateral neopallial lesions or no further operation. Removal of the superior cervical ganglia prevented the anomalous innervation of the remaining hippocampal tissue. All animals then learned a conditioned taste aversion to a sweetened milk solution (CS) following LiCl-induced gastrointestinal illness (UCS). The rats with hippocampal lesions were significantly slower to extinguish the aversion conditioning across the 14 day recovery period than were controls. There was no effect of any manipulation on the acquisition of the conditioned taste aversion, and there were no behavioral consequences of the presence or absence of the anomalous innervation. The slower extinction of the taste aversion shown by the hippocampal lesioned rats was discussed in terms of a lessened impact of the pre-illness exposure to the CS in these animals.

The effect of cue distinctiveness on successive discrimination performance in hippocampal lesioned rats

Twenty rats received bilateral lesions at three levels of the hippocampus, 20 received bilateral lesions of the amygdaloid complex, and 20 served as unoperated controls. Sets of lesion groups were trained on one of four discrimination tasks differing in stimulus dis­ tinctiveness. I t was found that hippocampal lesioned rats were deficient on those tasks low in cue distinctiveness but similar to controls on those tasks high in cue distinctiveness. A control experiment showed that these findings could not be explained in terms of a failure of hippocampal lesioned rats to habituate to an irrelevant tactile stimulus present in those discrimination tasks in which hippocampallesioned rats were deficient. Rats with hippocampal lesions are said to per­ severate because of an inability to suppress or stop the initiation or execution of prepotent responses. Thus, deficits in the learning of a new task may be the result of perseveration on an old task. Since successive discrimination impairments in hippocam­ pal lesioned rats can be interpreted as a result of perseveration on the response against which dis­ crimination learning is measured (Douglas, 1967; Isaacson, Schmahz, & Douglas, 1966), the aim of the present experiment was to determine whether per­ severation was an inevitable consequence of hippo­ campectomy in rats, or whether it varied as a func­ tion of cue distinctiveness. Since it has been shown that rats with hippocampal lesions are less distracted by irrelevant stimuli during a trained runway response (Raphelson, Isaacson, & Douglas, 1965; Riddell, Rothblatt, & Wilson, 1969; Wickelgren & Isaacson, 1963), it might be expected that hippocampallesioned rats would not notice the relevant stimuli in a runway go, no-go successive discrimination task. EXPERIMENT 1 Stimuli were used which were thought to vary in distinctiveness because of the inherent dominance of certain sensory modalities in the rat and because of the inherent sensitivity of the rat to certain stimulus dimensions. Tactile stimuli (roughness and tempera­ ture) were used as highly distinctive stimulus dimen­ sions, while visual stimuli (brightness and orientation) were used as relatively indistinct dimensions. Further, it could be suggested that brightness was relatively higher in distinctiveness than the orientation di­ mension.

Effect of bilateral hippocampal lesions on cue utilization in the rat.

8 albino rats received bilateral lesions of the hippocampus, 8 received bilateral lesions of the amygdaloid complex, and 8 served as unoperated controls. The rats were trained to find food at the end of an arm of a cross-maze, associated with a conspicuous light stimulus as the first task. Rats were required to relearn the first task with the light stimulus absent. Hippocampal-lesioned rats did not differ from controls on the first task but showed a large deficit on the second task.

Cue utilization and hippocampal lesions in rats

Hippocampal lesioned and sham-operated control rats were trained on a go, no-go task to assess the importance of multiple relevant cues on learning. When one stimulus (e.g., a light) was presented during the go trials and a second stimulus (e.g., a tone) was presented during the no-go trials, the lesioned animals performed more poorly than the control animals. However, when a light-tone combination was presented during the go (or no-go in a second condition) trials, and their absence signified the no-go trials (or the go trials), the performance of the lesioned and control animals did not differ. The data suggest that the use of multiple cues in an operant go, no-go discrimination task does not necessarily eliminate the learning deficit typically seen on this task by animals with hippocampal lesions. The manner in which these cues are presented is also important.

Persistent spatial maze-learning deficits in hippocampal-lesioned rats across a 7-week postoperative period

Rats with bilateral dorsal hippocampal lesions were tested on a series of three Rabinovitch-Rosvold maze patterns at either 1 week (Days 6, 7, and 8) or 7 weeks (Days 48, 49, and 50) following surgery. All rats in both groups were significantly impaired in the acquisition of these complex spatial maze patterns, regardless of the postoperative delay prior to testing. This lack of improvement stands in sharp contrast to earlier findings from our laboratory, in which it was determined that the decrease in levels of spontaneous alternation and the alterations in open-field activity produced by hippocampal lesions did return to normal levels within 6 weeks following surgery. The present results indicate that spatial maze learning may be classified as a persistent (although perhaps not permanent) deficit produced by hippocampal damage.

Epileptiform lesions in rat hippocampus and acquisition of two-way avoidance

Three experiments were conducted to examine the effects on the acquisition of two-way active avoidance of implantation into the hippocampus of rats of two substances (aluminum hydroxide, penicillin) known to produce epileptogenic electrical discharges. In Experiment 1 bilateral deposits of aluminum hydroxide (ALOH) were placed in the hippocampus and the effects of this manipulation were compared to the effects of bilateral hippocampal aspiration. Sufficient postoperative time (130 days) was allowed such that epileptogenic discharges developed in the ALOH-implanted rats. Both bilateral hippocampal-ALOH deposits and bilateral hippocampal aspiration resulted in facilitated acquisition of the two-way avoidance. The results of Experiment 2 replicated this observation, but also indicated that bilateral hippocampal deposits of penicillin did not cause detectable effects on acquisition of the avoidance. Epileptiform activity produced by the penicillin was observed to disappear by postoperative Day 4. In Experiment 3 unilateral hippocampal/aspiration was combined with contralateral implants of either ALOH or penicillin and avoidance training was begun 13 days postoperatively. Epileptiform activity was not observed in the ALOH-implanted rats and disappeared by postoperative Day 4 in the penicillin implanted rats. No significant changes were observed in the rate of acquisition of two-way active avoidance as a result of the manipulations done in Experiment 3. It is concluded that epileptiform discharge initiated focally within the hippocampus produces effects on the acquisition of two-way active avoidance which are similar to the effects produced by bilateral ablation.

Changes in behavior of hippocampal-lesioned rats across a 6-week postoperative period

The postoperative behavior of rats with one-stage bilateral lesions of the dorso-lateral hippocampus was examined preoperatively and on 15 separate occasions over a 42-day postoperative period. Repeated measures of spontaneous alternation in a T-maze and general activity in an open field were made. The postoperative behavior of the hippocampal-lesioned rats was compared with that of control rats which had sustained one-stage bilateral lesions of the neopallium overlying the hippocampal formation. The effect of the neopallial lesion on both behaviors was transitory; preoperative levels of behavior returned within 72 h postoperatively. For the hippocampal-lesioned group there was a drop in the level of spontaneous alternation on Day 2 postoperatively, a brief return to preoperative levels on Day 3, and then a sustained depression in rate until Day 14, when a return toward preoperative alternation rates occurred. In the open field, the hippocampal-lesioned subjects displayed a 3-4-day period of hypoactivity, followed abruptly by a 7-9-day period of hyperactivity. These subjects then returned to preoperative levels of activity. The nature and time course of these shifts in postoperative behavior were discussed in terms of their possible relationship to findings regarding synaptic reinnervation of the septal nuclei.

Effects of hippocampal x-irradiation-produced granule-cell agenesis on instrumental runway performance in rats

Rats in which x-irradiation during early postnatal life had interfered with the acquisition of dentate granule cells ran faster than controls during extinction of a runway response acquired under a consistent food reward schedule. A training schedule of randomly rewarded and nonrewarded trials increased running speeds to an equal extent in x-irradiated and control groups during extinction. The second and third experiments showed that unlike a reported total inability of hippocampal lesioned rats to pattern their running responses appropriate to a single alternation schedule of reward and nonreward, x-irradiated rats, while impaired in acquiring response alternation, did pattern and had persistent deficits compared to controls only when the task was made very simple by reducing the number of daily trials to two. The results are discussed in terms of an hypothesized reduction in the aversiveness of nonreward and a consequent reduction in the growth of inhibition in x-irradiated rats.

Effect of a physical barrier on response perseveration in hippocampal lesioned rats

Hippocampal lesioned and sham operated rats were required to relearn entry into a previously learned reinforced side arm in a T-maze from a new starting position 180 degrees from the original location. Half of each operated group were allowed free access while the other half had to open clear plastic doors to gain entry into the side arms. Only those hippocampal lesioned rats allowed free access to the side arms failed to relearn the entry response in fewer errors or with significant slower running speed than in the initial task. Both sham operated subgroups and the obstructed hippocampal lesioned group of rats learned the second task in fewer errors and displayed running speed disruption. The results were discussed in terms of a deficit of internal inhibition due to the limbic damage.

Hippocampal lesions and the partial reinforcement effect.

Two hypotheses of hippocampal function predict that nonreinforcement effects should be attenuated in hippocampal-lesioned rats. As a test of these hypotheses, hippocampal-lesioned and normal rats were trained in the straight runway on continuous or partial reinforcement schedules and then extinguished. In acquisition, lesioned rats ran slower over-all than normals and slower on trials following reward than normals, but there was no difference on trials following nonreward. In extinction, although lesioned Ss with continuous reinforcement were more resistant to extinction than normals, there was little difference between lesioned and normal groups having partial reinforcement and no significant attenuation of the partial reinforcement effect. The results were interpreted as implicating the hippocampus in the mediation of reinforcement rather than nonreinforcement effects.

Pre- and post-operative approach training and conflict resolution by septal and hippocampal lesioned rats

Pre- and post-operative approach training was found to have differential effects on rats with septal or hippocampal lesions in an approach-avoidance conflict. Trained to run a straight alley for food reinforcement, the septal lesioned animals who received approach training after surgery showed less inhibition upon the introduction of shock than the septal group who received pre-operative approach training. The animals with hippocampal lesions however, showed a greater loss of inhibition when pre-operatively trained to approach. On the trials on which the lesioned animals did demonstrate behavioral inhibition the spatial location of approach-avoidance conflict was similar to the control animals. The results suggest that the effect of septal lesions in an approach-avoidance situation is determined, to a considerable degree, by post-operative approach training whereas the effects of hippocampal lesions appear to interact with pre-operatively determined set.

Spontaneous activity in septal and hippocampal-lesioned rats.

30 rats were assigned in equal numbers to control, hippocampal, and septal groups. Ss were observed in a novel situation for three 15-min. sessions with 24 hr. between sessions and measures taken of their sniffing, walking, and grooming rates. The most important difference occurred in the third session when it was found that the type of lesion exerted control over the habituation of different responses. In walking, there was a tendency for Ss in the hippocampal and control groups to decrease their rate over time, while septal-lesioned Ss tended to increase their rate. Both septal and control groups decreased their sniffing rate, whereas the hippocampal group did not. In grooming, neither the hippocampal nor the septal group showed an increase in rate, whereas the control Ss did. The results of the septal-lesioned Ss were regarded as consistent with a conventional response-inhibition hypothesis while the data of the hippocampal group suggested a deficit in attentional mechanisms.

Behavior of hippocampal lesioned rats in home cage and novel situations☆

Abstract A time-sampling observation procedure was used to record behavior of hippocampal damaged and control rats in home cage and novel open field under both ad libitum and food deprivation conditions. In the home cage hippocampal animals slept less than controls under both conditions. There were no differences between groups during the day but hippocampal rats spent significantly more time sniffing and were more active during the night. In the novel open field containing food pellets, hippocampals were more active than controls in the ad libitum condition and habituated at the same rate, whereas, under deprivation hippocampal rats were more active early in the session but later spent more time than controls with the food. These results are interpreted as evidence for a motivational involvement of the hippocampus.

Open-field behavior of hippocampal-lesioned rats and hamsters.

Open-field behavior of hippocampal-lesioned rats and hamsters.

Patterns of behavior of hippocampal lesioned rats in an exploratory motivated situation.

10 rats with bilateral dorsal hippocampal lesions and 16 control rats were pretrained in an unbaited T maze and then trained on a position habit reinforced by the opportunity for exploration. In comparison with the control Ss the hippocampal lesioned rats during pretraining perseverated more, made more maze-unit entries after some exposure, ran more slowly initially, and were less distracted by environmental change. During choice training the hippocampal lesioned rats perseverated more than control Ss and ran faster over days on forced trials. The results are consistent with a response inhibition interpretation of hippocampal function and emphasize the importance of pretraining and changes over time in interpreting the effects of hippocampal lesions.