Physiology & Behavior, Vol. 21, pp. 39--44.PergamonPress and BrainResearch Publ., 1978. Printedin the U.S.A.

Cue-Induced Recall of a Passive Avoidance Response by Rats with Hippocampal Lesions GORDON WlNOCUR

D~artment~P~cho~,TrentUniversi~,

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Ont~rio, C a n a ~ K ~

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AND A.H.

BLACK

M c M a s t e r U n i v e r s i ~ , H a m i l t o n , Ontario, C a n a ~ L 8 S 4 K 1 ( R e c e i v e d 24 N o v e m b e r 1977)

WINOCUR, G. AND A. H. BLACK. Cue-induced recall of a passive avoidance response by rats with hippocampal lesions. PHYSIOL. BEHAV. 21(1)39 44, 1978.--Twoexpedments are reported in which a stimulus reminder technique was used in an attempt to compensate for the disruptive effects of hippocampai lesions on passive avoidance (PA) conditioning. Groups of hippocampal, cortical and operated control rats were trained to run down an alley for water reward. When the approach response had stabilized, shock was introduced in the goal-box, resulting in increased running times in the control groups and the characteristic PA impairment in the hippocampal group. A recall test was administered 24 hr later but 2 hr before the test, animals were reminded of the previous treatment by being exposed to: (1) shock and related stimuli, (2) related stimuli only, or (3) neutral stimuli. The PA performance of the hippocampus groups in the recall test improved to the level of controls folowing conditions 1 or 2; there was no effect of condition on Treatment 3. Performance of control groups was virtually unaffected by any of the reminder conditions. The similarities were noted between these results and those of partial cueing studies involving human amnesics with known or suspected damage to the hippocampal system. Hippocampus

Passive avoidance

Stimulus reminder

BILATERAL lesions to the hippocampus typically impair passive avoidance (PA) learning in runway situations when a previously rewarded approach response is punished by electric shock [8,10]. This deficit has been frequently attributed to a lesion-induced response disinhibition [1, 3, 11] but numerous reports of normal response suppression by hippocampal animals in a variety of tasks, including nonrunway tests of PA, contradict this position [4, 16, 22]. Recent work by Winocur and Bindra [25] suggests that the hippocampal PA deficit in runways is due to an impaired use of available cues. These investigators observed that the essential difference between hippocampal and control groups of rats in a standard runway was the point at which approach behavior was inhibited. For the controls, approach behavior was inhibited shortly after they left the start area; for the hippocampals, approach behavior was not inhibited until they were about two-thirds of the way down the alley.

Significantly, the rats with hippocampal lesions sustained no more shocks than controls throughout the entire five trial PA training period. Thus, it appeared that, while rats with hippocampal lesions were responsive to goal box cues associated with punishment, they were unable to relate their aversive experience to more remote cues at the beginning of the runway. Similar results have been obtained by Black, Anchel, Barbaree and Okaiche [6] in rats with fornical lesions. Animals with hippocampal damage are generally impaired on tasks which are preceded by training on related problems, a feature which also characterizes the deficit pattern of humans with damage to the hippocampal system. It has been suggested that the hippocampus plays a major role in reducing interfering influences, thereby contributing to the retrieval of acquired information and response selection [21]. Retrieval deficits can be identified through the use of partial

1The research was supported by grants from the National Research Council of Canada to Gordon Winocur (APA-8181)and A. H. Black (APA-0042). ZThe technical assistance provided by Mr. B. Osborne, Mr. J. Zomer, and Ms. Wendy Young is gratefully acknowledged. :3Requests for reprints should be addressed to Dr. Gordon Winocur, Department of Psychology, Trent University, Peterborough, Ontario, Canada, KgJ 7B8.

C o p y r i g h t © 1978 B r a i n R e s e a r c h P u b l i c a t i o n s Inc.--0031-9384/78/0701-0039502.00/0

40

W I N O C U R AND BLACK

cueing techniques in which components of the original stimulus material are presented at retention testing and, serving as prompts or reminders, facilitate the recall of apparently lost memories. Such methods have been successfully applied to human amnesics with known hippocampal damage [21], providing support for the hypothesis that the hippocampus is involved in the retrieval of information. Analogous cueing techniques have also been employed with animals rendered amnesic by electroconvulsive shock (ECS) or other amnestic agents (see [14]). For example, Lewis, Misanin, and Miller [13] trained rats on a PA task and immediately administered ECS. Before retesting, noncontingent foot shock was given to one group which, in contrast to controls, subsequently displayed good recall of the avoidance response. The present research was designed to see if partial cueing techniques could be used to compensate for the deleterious effects of hippocampai lesions in rats. If, as has been suggested [25], the PA deficit of hippocampally-damaged rats is related to an inability to use available stimulus cues, it may be possible to improve their performance by providing reminder cues which emphasize the aversive aspects of their training experience. This type of demonstration would represent an important parallel between the animal hippocampal and human amnesic syndromes. EXPERIMENT 1

Method Animals. Forty-five, naive, male, Wistar rats, weighing 300-350 g were obtained from the Animal Breeding Centre, Trent University, and used as subjects. Throughout the experiment, animals were housed individually in wire cages with food available at all times and water provided according to experimental conditions. Surgery and histology. In preparation for surgery, animals were anesthetized with sodium pentobarbital and positioned in a Johnson-Krieg stereotaxic instrument. Bilateral hippocampal and cortical lesions were produced by passing a 2 mA anodal DC for 20 sec through a stainless steel electrode, insulated except for 0.5 mm at the tip. Electrode placements were stereotaxically oriented at 2.2 mm posterior to bregma, 1.5 mm-2.00 mm lateral to the midline,and 3.0 mm below dura for the hippocampal lesions. The same anterior-posterior and lateral coordinates were used for the cortical lesions but the electrode was lowered only 1.5 mm below dura. Operated controls were prepared in the same manner but no electrode was lowered. At the completion of testing, all brain-damaged animals were perfused with physiological saline followed by 10% formol saline. The brains were removed and fixed in 10% formol saline for several days. Subsequently, frozen sections were made in the transverse plane and every fifth section stained with thionine. The ablated areas were identified using the stereotaxic atlas of K r n i g and Klippel [12]. Apparatus. The apparatus consisted of a straight runway (125 × 13 × 15 cm), divided into a start area (25 cm long), an alley (75 cm), and a goal box (25 cm). A water spout protrnded through the back of the goal box which had a grid floor and white painted wood walls. The walls and floor of the rest of the runway and start box were made of wood and painted flat grey. A manually-operated guillotine door separated the start area from the alley. Photocells attached to a Hunter timer were located at the mid-point of the alley. Timers were

also hooked up to the guillotine door and water spout. The timing sequence for each trial was initiated when the guillotine door was raised, closing a microswitch, and terminated when the animal made contact with the spout. Raising the guillotine door also had the effect of activating the alley timer, which was automatically turned off when the animal broke the beam of the photocells. The spout was also attached to a Lafayette Co. shock generator (model No. 5226) which, on designated trials, delivered a 3 mA current to the animal standing on the grid floor. The apparatus was located away from the walls and in such a way as to minimize the availability of external room cues. General illumination was provided by overhead fluorescent illumination. There were two reminder boxes, one being an exact replica of the goal box except for the water spout, which was absent in the reminder box. The grid floor of this box was attached to a shock source which passed a 3 mA current. The other reminder box was larger (30 × 25 × 20 cm) and had Plexiglas walls and floor with no electrical attachments. Procedure. Animals were allowed to recover from surgery for about 10 days and were then placed on a 23 1/2 hr water deprivation schedule. F o r five days, animals were handled for about 15 min after each watering session. A two day habituation period followed in which pairs of animals were placed in the runway for 45 min each day, permitted to explore and drink from the water spout in the goal box. Twenty-four hr after the second habituation session, approach training was instituted. Each approach trial consisted of placing the animal individually in the start area, lifting the guillotine door, and allowing the animal to cross the alley and drink in the goal box for about 10 sec. Ten trials per day were administered on four consecutive days. On the fifth training day, animals received five trials as usual, followed by five trials in which the water spout was electrified. On these trials, water was available but upon making initial contact with the spout the animal received an electric shock which turned off when contact was broken. No further shock was administered on that trial, and the animal was free to drink for 10 sec. Subsequent trials were terminated if the animal failed to reach the mid-point of the runway within 60 sec of having left the start box. When this occurred, the animal returned to its home cage and scores of 60 sec were assigned for each half of the runway. If the animal reached the second half of the runway within this period, the trial continued until contact was made with the water spout or 60 sec had elapsed. Throughout testing, animals were run in groups of three or four, with an inter-trial interval maintained at about three min. The next day, two hr before retesting, animals were placed individually in one of the reminder boxes. The boxes were located in a different part of the testing room than the runway. Those groups (hippocampal, N = 8; corticals, N = 6; operated controls, N = 4) receiving partial cueing were placed in the white box and administered brief pulses of foot shock for the entire two min (WBS Condition). The other groups (hippocampal, N = 12; cortical, N := 9; operated control, N = 6) were merely detained in the neutral Plexiglas Box (NB Condition).

Results There were no differences between the cortical and operated control groups on any of the measures and so their data were combined to constitute single control groups in each cue condition. Figure 1 presents hippocampal and con-

CUE-INDUCED RECALL OF AVOIDANCE RESPONSE EXPERIMENT I NEUTRAL

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FIG. 1. First and second half runway latencies for hippocampal and control groups in the last pre-shock trial, the last shock trial, and the recall trial in Experiment 1.

trol groups' running times for the last pre-shock trial, the last shock trial, and the recall test for the WBS and NB conditions. Pre-shock. All groups learned the water-reinforced approach response to asymptotic level within the 40 trial training period. Although there was a tendency for animals in the WBS condition to run faster, there were no significant differences in the pre-shock measure between or within the cue conditions (ANOVA, all p's>0.05). Shock. Following the introduction of shock, as expected, hippocampal animals ran down the alley more than controls and generally exhibited shorter running times than controls. A 2 × 2 A N O V A was applied to shock trial five scores;

41 one main factor was lesion and the other was segment. It revealed a significant lesion by segment interaction, F(1,43) = 12.06;p0.05; NB: t < l . Animals in the NB condition generally exhibited more PA than those in the WBS condition in the first half of the runway. t-test analyses of the data revealed significant differences between hippocampal t(18) = 5.40; p

Cue-induced recall of a passive avoidance response by rats with hippocampal lesions.

Physiology & Behavior, Vol. 21, pp. 39--44.PergamonPress and BrainResearch Publ., 1978. Printedin the U.S.A. Cue-Induced Recall of a Passive Avoidanc...
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