Anterograde and Retrograde Amnesia in Rats with Dorsal Hippocampal Or Dorsomedial Thalamic Lesions

Behavioural Brain Research, 38 (1990) 145-154 145 Elsevier BBR01052

Anterograde and retrograde amnesia in rats with dorsal hippocampal or dorsomedial thalamic lesions

Gordon Winocur Trent University, Peterborough, Ont. (Canada)

(Received 5 July 1989) (Accepted 9 January 1990)

Key words: Hippocampus; Thalamus; Anterograde amnesia; Retrograde amnesia

The present research was concerned with anterograde and retrograde memory for a socially transmitted food preference in rats with lesions to the dorsal hippocampus or dorsomedial thalamus, and operated controls. In Expt. 1, food-preference training was administered postoperatively and memory was tested following various delays. Both lesioned groups acquired the preference normally, but rats with hippocampal lesions displayed a rapid rate of forgetting that indicated significant anterograde amnesia. In Expt. 2, the food preference was acquired at different times preoperatively and retrograde memory was tested postoperatively. Both lesioned groups exhibited loss of memory when training immediately preceded surgery, but only rats with hippocampal lesions displayed a temporally-graded retrograde amnesia. The results confirmed the differential effects of hippocampal and thalamic lesions on memory performance. It was suggested that memory loss following thalamic lesions was related to factors associated with original learning, whereas the pattern ofhippocampal amnesia reflected disruption at a later stage in the learning process.

INTRODUCTION differ in the two cases. Memory for preoperative events has been studied only occasionally in ani- The characteristic feature of the human mal populations (e.g. refs. 23,38) and there have amnesic syndrome is a profound memory loss for been no investigations of temporally-graded RA. events that occur subsequent to brain insult (ante- Undoubtedly, the development of animal models rograde amnesia, AA). Memory loss for pre- of RA has been hampered by the lack of suitable morbid events or retrograde amnesia (RA) is paradigms. In particular, it has been difficult to more variable, ranging form very little in some devise tasks that meet two crucial conditions for cases to considerable amounts that can extend testing remote memory. First, the test must assess back several decades 4'6'22"28. Attempts to relate memory for events that can be identified with a severity of RA to severity of Am 24'30, to etiologic al specific time period and, second, it must be possi- factors 2°, or to locus and extent of lesion 32, have ble to show that memory for the information de- generally been unsuccessful. grades normally over a manageable test interval. Investigations of memory loss in brain- The above conditions are met in a test originally damaged animals have confirmed that lesions to developed by Galef8'9 to study socially acquired the hippocampal system 13"36,38 or the dorso- food preferences in rats. The basic procedure in- medial thalamus 1,36,38 produce severe AA, volves pairing a naive subject rat (S) with a de- although the precise nature of the deficits may monstrator rat (D) that has recently sampled a

Correspondence: G. Winocur, Department of Psychology, Trent University, Peterborough, Ont., Canada, K9J 7B8.

0166-4328/90/$03.50 © 1990 Elsevier Science Publishers B.V. (Biomedical Division) 146 particular food substance. By interacting with D, at short delays, if they are deficient in originally S acquires a preference for that food that persists acquiring the food preference. Conversely, if they at a declining rate over several days. Preliminary acquire the preference normally, little or no investigation in our lab showed that slight impairment is predicted. These predictions were variations in Galef's procedure can produce food tested in Expt. 1. preferences that last even longer, so that the test becomes suitable for assessing more remote Me~o~ memories. The modified procedure was used to continue Subjects and apparatus our comparison of the effects of hippocampal and A total of 129 male, Long-Evans rats served as thalamic lesions on memory performance. Pre- Ss and an additional 20 rats of the same strain vious studies were restricted to postoperatively served as Ds. All rats were obtained from the acquired memories 36. In the present research, this Trent University Breeding Centre and were work was extended to an assessment of retro- 7-10 months old at the time of the experiment. grade memory for information acquired at various Prior to the experiment, the rats were housed times before brain damage. individually in standard wire cages (25 × 18 x 18 cm) with food and water available EXPERIMENT1 at all times. Testing took place in larger cages (42 x 24 x 27 cm), divided into two equal com- In previous tests of postoperative learning and partments by a 1.25-cm wire mesh partition. D memory involving delayed alternation and pas- and S rats were placed individually in each com- sive avoidance tasks (Winocur, 1985), rats with partment. dorsal hippocampal lesions performed normally when required to retain specific information for Surgery and histology relatively brief periods of time, but were severely The surgical procedure was identical to that impaired as the length of the interval increased. described in previous studies (e.g. ref. 36). Rats Rats with dorsomedial thalamic lesions were were anaesthetized with sodium pentobarbital impaired at both short and long intervals on the and positioned in a Johnson-Krieg stereotaxic delayed alternation task, a task on which they also instrument with the tooth bar raised to a height of displayed poor initial learning. On the passive 5 mm above the interaural plane. Bilateral electro- avoidance task, they acquired the avoidance lytic lesions were made by passing a 2-mA direct response as well as controls and showed the same current through a stainless steel electrode insulat- rate of forgetting over time. The overall pattern of ed except for 0.5 mm as a tip. Stereotaxic coordi- results was similar to that observed in clinical nates for the hippocampal lesions were 2.2 mm studies 11'26 and was similarly interpreted as impli- posterior (P) to bregma, 1.5 and 2.5 mm lateral cating the thalamus in a fundamental encoding (L) to the midline, to a depth (D) of 3.0 mm below operation that occurs very early in the learning dura. For dorsomedial thalamic lesions, the process. The hippocampus, on the other hand, coordinates were 1.5 P, 1.0 L, 4.5 D. Rats in the was seen to be important for integrating recently operated control groups received an incision, acquired information within the existing knowl- holes were drilled in their skulls, but no electrode edge structure, thereby contributing to the con- was lowered. solidation or storage of new information. Following testing, all brain-damaged animals By this view, in the Galef paradigm, rats with were deeply anaesthetized with ether and per- hippocampal lesions should recall postoperatively fused intracraniaUy with physiological saline fol- acquired food preferences as well as normal rats lowed by 10% formol-saline solution. The brains at short intervals but show faster forgetting as the were removed and fixed in 10~o formol-saline for length of the interval increases. Rats with 7 days. Transverse sections were subsequently thalamic lesions should show memory loss even made and every 5th section throughout the lesion 147 was mounted and stained with thionin. Extent of and the other containing the cinnamon-flavoured damage was determined by a comparison with the diet. After 2 h, both food cups were weighed and standard atlas of KOnig and Klippell TM. diet intakes calculated. (The 2-h test session was a departure from Galef and Wigrnore's procedure Procedure and was adopted because preliminary obser- Rats were allowed at least 2 weeks to recover vations indicated that, during this time, S rats from surgery, during which time they were showed their strongest preference before sam- maintained on an ad libitum food and water diet, piing, in increasing amounts, the non-preferred and handled periodically. One week before the food. In other words, a shorter test period provid- experiment, D and S rats were placed on a 23½-h ed a more sensitive measure of recalled prefer- food deprivation schedule. Typically, 12 pairs of ence.) rats were studied at one time. The experimental In addition to the 0 delay condition, different procedure conformed closely to that described by groups of S rats were tested at delays of 1, 2, 4, Galef and Wigmore9 and consisted of 5 discrete or 8 days following D-S interaction. During these steps: (1) D and S rats were transferred in pairs delays, Ss were returned to their home cages. from their home cage to compartments in the test Once a day, they were given 20 g of rat chow in cages, and allowed to become familiar with each pellet form. After the delay, Ss were returned other and the new environment. Rats were left individually to the test compartment and given undisturbed 2 days during which time they were cinnamon- and cocoa-flavoured diets in the usual fed rat chow on an ad libitum basis. (2) Food was manner. removed from both cages for 23 h. (3) D was removed to another room and, for 60 min, fed Results and Discussion powdered rat chow adulterated 2~o by weight with commercially prepared sifted cocoa or 1 ~o None of the groups displayed a preference for commercially ground cinnamon. (4)D was re- either the cocoa or cinnamon in any of the tests. turned to its compartment beside S and the 2 rats Accordingly, the data for each diet as sample were were allowed to interact across the partition for combined and are presented in Fig. 1 as the per- 15 min. (5) D was removed from the cage and, in centage sample diet of the total amount eaten by the 0 delay condition, S was offered 2 weighted Ss at each delay period. food cups, 1 containing the cocoa-flavoured diet As can be seen in Fig. 1, at 0 delay, all groups

ANTEROGRADE

CONTROL HIPPOCAMPAL THALAMIC 100 I00 T i N 9o i g0 T T 80

r.1 oZ ~ 70 70 I.T~ ~ ~ 60 ~.1 r-1 60

50 50

01248 0 1 2 4 8 0 1 2 4 8

DAYS BETWEEN ACQUISITION AND TEST Fig. 1. Mean percentage of sample diet ingested by all groups at the various delays of Expt. 1. Bars indicate _+ 1 S.E.M. 148 displayed an equally strong preference for the food preferences were well established pre- sample diet. It may be noted that, in line with operatively, the effects of dorsomedial thalamic preliminary observations, the groups displayed lesions on recall would be minimal. On the stronger preferences for the sample diet at 0 delay other hand, if as it would appear, the hippocam- than typically observed by Galef in his experi- pus contributes to the long-term storage of newly ments 8'9. This is probably because of procedural acquired information, then preoperatively pre- differences at testing. As indicated in the Methods sented information that is inadequately repre- section, in the present study the food cups were sented, should be vulnerable to the effects of weighed after 2 h, whereas Galefmeasured prefer- dorsal hippocampal lesions. Accordingly, by va- ences over a 12-h period. Although the preference rying the time between learning and surgery, it decreased over time in all groups, the rate of de- may be possible to demonstrate temporally- cline was fastest in rats with hippocampal lesions. graded RA in rats with dorsal hippocampal These observations were confmned by analysis of lesions. These predictions were tested in Expt. 2 variance in which groups and days were treated as using acquired food preferences as the measure of between variables. The group x day interaction memory function. was highly significant (Fs.114 = 3.04, P< 0.01) and due entirely to the smaller percentage of Methods sample diet eaten by the hippocampal group at delays of 2, 4, and 8 days. Tukey tests indicated Subjects significant differences between the hippocampal A total of 102 naive, male Long-Evans rats, groups and the other groups at all 3 delays approximately 6 months old, obtained from the (P's < 0.05). There were no differences between Trent University Breeding Centre, were subjects groups at 0 and 1 day delays, and the control and in this experiment. Twenty rats who served as thalamic groups did not differ from each other at control subjects in Expt. 1 acted as Ds in Expt. 2. any time. All rats were housed individually in wire cages A faster rate of forgetting by rats with hippo- and handled occasionally for 2 weeks before the campal lesions was confirmed by trend analysis experiment. on the percentage eaten at each test period. These analyses indicated a significantly different trend in Procedure the hippocampal groups than in the control All D and S rats were placed on a 23½-h food- (F1.75 = 4.36, P< 0.05) and thalamic (F1,76 = deprivation schedule 1 week before they were due 7.48, P < 0.01) groups. to be transferred to the test cages. Rats were then subjected to steps 1-4 of the experimental proce- EXPERIMENT2 dure described in Expt. 1. The only difference was that, in step 4, D and S were allowed to interact In Expt. 1, rats with dorsal hippocampal or for 30 min rather than the 15 min of Expt. 1. The dorsomedial thalamic lesions initially acquired reason for this was to establish a stronger food the food preference as well as operated control preference that was more likely to endure over the rats, but the thalamic groups retained the prefer- extended delays that applied in Expt. 2. ence better over an 8-day period. These results are After step 4, S rats were subjected to dorsal consistent with previous observations 36 that rats hippocampal, dorsomedial thalamic, or operated with dorsomedial thalamic lesions are unlikely to control surgery immediately, 2, 5, or 10 days later. display significant memory loss if the material is S rats that were not scheduled for immediate sur- well learned. In contrast, rats with dorsal hippo- gery were returned to their home cages and given campal lesions retained the information only for 20 g of food in pellet form. They were maintained relatively brief periods and then showed rapid on this feeding schedule until surgery. forgetting thereafter. After surgery, rats were placed on ad libitum It follows from the above pattern that if the food for 5 days, followed by 23½-h food-depri- 149 vation schedule for 5 more days. Testing occurred and delay periods treated as between-factors re- for all rats at 10 days postsurgery. This meant that vealed a significant group x day interaction S rats, in the various groups, were tested 10, 12, (F6.9o = 8.87, P < 0.001). Further analysis with 15, or 20 days after step 4 in which they interacted the Tukey test indicated significant group differ- with the sample-fed D rats. ences at the 0 delay test, where the operated con- After the experiment, brain-damaged rats were trol group differed from the hippocampal and sacrificed, perfused, and their brains prepared for thalamic groups (P's < 0.01) and at the 2-day histological analysis in the manner described in test, where the hippocampal group differed signifi- Expt. 1. cantly from the thalamic and operated control groups (P's < 0,01). No other group differences Results and Discussion at the various delays were statistically significant. Comparisons within each lesion group across The results are presented in Fig. 2 and ex- delay intervals yielded a number of significant pressed as the percentage food sampled by each differences. Operated control groups tested at 0 lesion group at the various delay periods. Once and 2-day intervals differed significantly from the again, there were no significant preferences for operated control group tested at 10 days original food and so the data for each sample diet (P's < 0.05). The 0 delay thalamic group differed were combined. significantly from thalamic groups tested at the The first thing to note in Fig. 2 is that the other delay intervals (P's < 0.01). Amongst the forgetting patterns varied between groups. The hippocampal groups, those tested at 0 and 2-day operated control groups' preference for the delays differed significantly from those tested at 5 sample diet was strongest at 0 delay and declined and 10 days (P's < 0.05), but differences within progressively with longer delays. The thalamic each pair were not statistically significant. group showed only chance recall when the food Several points can be made on the basis of the preference was established immediately before results of Expt. 2. As expected, operated control surgery, but normal recall at the other delays. The rats showed strongest memory for the most re- hippocampal groups were no better than chance cently acquired food preferences with progres- at recalling the preference at 0 delay but showed sively declining performance at longer delays. In recovery between 0 and 5 days before dropping to contrast, dorsal hippocampal or dorsomedial normal levels at the 10-day delay. thalamic lesions abolished memory for the food An analysis of variance with lesioned groups preference when surgery was performed im-

RETROGRADE

CONTROL HIPPOCAMPAL THAIAMIC I00 100

90 90

cnt-~ --T_ T T 80 T 80 T 70 T T ITp70 oo l 60 50 50

0 2 5 i0 0 2 5 10 0 2 5 10

NUMBER OF DAYS BETWEEN ACQUISITION AND SURGERY

Fig. 2. Mean percentage of sample diet ingested by all groups at the various delays of Expt. 2. Bars indicate _+ 1 S.E.M. 150 mediately after the preference was established. of Expts. 1 and 2 were similar to that described When the delay between food preference acqui- in previous experiments using the same surgical sition and surgery was extended to 2 days, rats procedures (e.g. ref. 36). with dorsomedial thalamic lesions recovered to Hippocampal lesions produced extensive dis- normal levels. Rats with dorsal hippocampal ruption of the dorsal hippocampal formation lesions did not attain normal preference levels between 3.0 and 5.0 mm anterior to the interaural until the delay was extended to 5 days, indicating plane. Varying amounts of damage were observed a more gradual recovery. The results clearly indi- in the overlying cortex and corpus callosum, and cate preoperative memory loss following dorsal the hippocampal commissure and fimbria-fornix hippocampal or dorsomedial thalamic lesions. areas were frequently affected. In a few rats, slight The question as to whether the deficits observed damage was detected in dorsal thalamic nuclei. in the two lesion groups reflect disruption of Thalamic lesions consistently destroyed the similar or qualitatively different mechanisms will entire dorsomedial nucleus. In all cases, the be considered in the General Discussion. paraventricular nucleus was extensively damaged. Damage frequently extended from anterior Anatomical report portions of the anterior dentate gyrus and, to Photographs of typical hippocampal and lesser degrees, the stria medullaris, habenular, thalamic lesions are presented in Fig. 3. The locus and lateral thalamic nuclei. and extent of brain damage noted in the animals GENERAL DISCUSSION

The results of Expt. 1 demonstrate the differential effects of dorsal hippocampal and dorsomedial thalamic lesions in recalling a postoperatively acquired food preference. Rats with dorsal hippocampal lesions normally recalled the preference at relatively short delays (24 h) but not at longer delays. This pattern was similar to that displayed by hippocampal groups in other test situations (e.g. refs. 13,36). In contrast, the thalamic groups did not differ from operated controls at any delays in Expt. 1. The normal memory of rats with dorsomedial thalamic lesions may relate to the fact they were able to establish the food preference as well as other groups. In previous work, significant memory loss has been observed in rats with thalamic lesions on tasks on which they were impaired during original learning (simultaneous visual discrimination35; delayed alternation36). In contrast, in a test of passive avoidance conditioning36, rats with thalamic lesions normally learned the avoidance response and proceeded to show excellent recall at all delay intervals. The similarities between these effects and the patterns of anterograde amnesia in patients with medial temporal lobe or di- Fig. 3. Photographs of cross-sections of representative hip- encephalic lesions have been discussed in pre- pocampal (above) and thalamic lesions. vious reports 26"35a. 151

Expt. 2 provided a test of retrograde memory memory that covered their early premorbid by comparing the effects of dorsal hippocampal period. Parallels between the animal and clinical and dorsomedial thalamic lesions on recalling a literature are very tentative at this point but it preoperatively learned food preference. Once would appear that the pattern of retrograde again a dissociation was observed between the amnesia exhibited by hippocampal groups in brain-damaged groups. Although either lesion Expt. 2 of the present research is at least similar abolished memory for the food preference when to that seen in amnesic patients with damage to acquisition immediately preceded surgery, rats the medial temporal lobe and, specifically, the with dorsomedial thalamic lesions recovered to hippocampus. normal levels when the interval between ac- In Expt. 2, rats with dorsomedial thalamic quisition and surgery was extended to 2 days. In lesions failed to recall the food preference only contrast, rats with dorsal hippocampal lesions did when the learning experience immediately pre- not attain normal performance levels until the ceded surgery. Since both thalamic and hippo- interval'was extended to 5 days, indicating a more campal groups showed absolutely no recall of the graded recovery. There were no differences food preference in the 0-day test, it is conceivable between any of the groups at the longest delay that the trauma associated with either type of period. brain surgery was sufficient to obliterate represen- It is important to note that the results of tations of very recent experiences. Interestingly, Expts. 1 and 2 cannot be attributed to naturally the patient B.Y. showed a pattern of retrograde occurring preferences for either of the sample memory loss that was very similar to that of the diets. In the first place, the cinnamon- and cocoa- thalamic groups in Expt. 1. B.Y. became severely flavoured diets yielded the same results for all amnesic after a suspected infarct in the para- groups in both experiments. Second, on several median artery produced restricted bilateral dam- test occasions in Expts. 1 and 2, rats with dorsal age to the medial thalamus. He had total amnesia hippocampal or dorsomedial thalamic lesions dis- for the 1 or 2 hours preceding the attack, but little played equal intake of both diets. On those occa- measurable loss for earlier events. Other patients sions, it is clear that experimental procedures con- with relatively circumscribed thalamic lesions tributed to memory loss for the food preference. have been reported with profound AA but with The overall pattern of results suggests that dif- little or no accompanying RA 25,28. On the other ferences in anterograde or retrograde memory hand, there are reports of severe RA in patients amongst the various groups reflect genuine dif- with thalamic lesions, who do not have a history ferences in memory performance. of alcoholism or Korsakoff Syndrome (see The behaviour of brain-damaged groups in ref. 19). These apparent contradictions need to be Expt. 2 may be compared with clinical studies of investigated further before conclusions can be premorbid memory which, despite their variable drawn regarding thalamic damage and retrograde results, indicate some interesting parallels. For memory loss. example, investigations involving the classic The results of the present research can be medial-temporal lobe amnesic patient, H.M., viewed against the continuing debate over revealed a remote memory loss that, depending on whether amnesia following brain damage reflects the material, can extend back several years prior a primary disruption of acquisition or retrieval to surgery ~5. Recently, Zola-Morgan etal. 39 processes. A simple retrieval-deficit interpretation studied retrograde memory in another amnesic received little support since hippocampal and patient (R.B.) with hippocampal damage. R.B. thalamic groups showed some normal memory in exhibited signs of memory loss for events that both experiments. While it is tempting to attribute occurred 1-2 years before the ischemic attack the RA of hippocampal groups in Expt. 2 to a that precipitated his amnesia. Although H.M. and retrieval deficit, it can be argued that temporally- R.B. displayed some retrograde memory loss, limited retrograde memory loss may be part of an both patients performed well on tests of remote information processing deficit that affects the 152 organization of new memories 21,29. RA that precise interaction with the D-rat. If, indeed, extends back for a limited period in hippocampal- retaining an acquired food preference in the Galef damaged subjects may be seen as another task reflects non-episodic or implicit memory, the manifestation of the basic acquisition deficit that present results would suggest that amnesia fol- produces AA. The results of Expts. 1 and 2 lowing damage to hippocampal regions is not ne- clearly identified the hippocampus with a time- cessarily restricted to highly specific events. related stage of the learning process and are gen- There is evidence that hippocampal lesions do erally in accord with this notion. not always produce effects on memory per- Several investigators have suggested that formance that would be predicted by commonly thalamic damage interferes with new learning by held views of lost and spared memory function. disrupting the process of encoding new informa- Several studies have shown that damage to the tionS'~l'26; but see ref. 32. Thus, material that is hippocampus in animals produces explicit and poorly registered early in learning is unlikely to be implicit memory loss (e.g. refs. 3,31,36). Other recalled correctly. The finding that rats with dor- studies have shown that deficits in explicit somedial thalamic lesions normally acquired a memory produced by hippocampal damage can socially transmitted food preference and, for the be reduced by task manipulations that includes, most part, displayed normal memory for that pre- for example, providing preoperative training 38 ference, supports this position. Moreover, as pre- and salient contextual cues 34. Taken together, viously indicated, other studies have shown that these results suggest that memory performance in animals or humans with thalamic damage are animals with hippocampal lesions depends on the more likely to show memory loss on tasks on demand characteristics of the task as well as the which they experience difficulty during original procedures used to assess memory. Similar obser- learning (e.g refs. 26,36). vations have been made by investigators of human Finally, it is important to consider the type of amnesia in assessing, for example, the influence of memory that was affected by brain damage in the instructional set on memory for specific informa- present research and how the results relate to tion in Korsakoff patients ~° or task-related var- current views on lost and preserved memories in iables that can affect rate of forgetting in H.M. 7 amnesia. It is widely held that lesions to hippo- According to Moscovitch ~v'18, such evidence campal or diencephalic regions disrupt recall of argues against the traditional view of independent specific or episodic events, while sparing memory memory systems concerned with explicit memory, for information that cannot be identified with a on the one hand, and implicit memory, on the particular context (e.g. general knowledge, skills, other. Instead, he has advocated a component- rules) (see reviews in refs. 16,27). If, in Galefs processes approach that emphasizes the cognitive task, remembering a food preference depends on operations required for successful performance recalling the specific experience in which the pre- on a particular task. By this view, memory tests ference was acquired, then the present results, at that depend on similar cognitive processes will least with respect to the hippocampus, are gener- yield impairment, whether they assess explicit or ally consistent with animal and human evidence implicit memory, when brain regions essential for for memory dissociation in amnesia. On the other mediating those processes are damaged. hand, the S rats may have displayed the food Applying this approach to the present study, preference without reference to their specific the food-preference task is seen as assessing encounter with the D rats. The initial learning memory for a specific food preference acquired experience may have 'primed' the Ss to favour during an episodic learning experience. However, that particular food in subsequent choice si- demonstrating that preference at a later time does tuations. If Ss initially acquired the preference by not depend on the exclusive contribution of an processing information related, for example, to explicit or implicit memory system. The prefer- taste and safety, that preference could be remem- ence can be maintained by recalling the learning bered later without necessarily recalling the episode, or by the more indirect influence of the 153 original experience on subsequent behaviour. The Human Memory and Amnesia, Erlbaum, Hillsdale, 1982, task draws on cognitive processes essential for pp. 257-275. 5 Butters, N. and Cermak, L.S., The role of cognitive acquiring and retrieving the preference and, as the factors in the memory disorder of alcoholic patients with results of Expts. 1 and 2 indicate, these processes the Korsakoff syndrome,Ann. N. Y. Acad. Sci., 233 (1974) depend on an intact hippocampus, but not neces- 61-75. sarily on an intact thalamus. 6 Cermak, L.S. and O'Connor, M., The anterograde and The present results point to dissociable retrograde retrieval ability of a patient with amnesia due to encephalitis, Neuropsychologia, 21 (1983) 213-234. functions between hippocampus and thalamus 7 Freed, D.M. and Corkin, S., Rate of forgetting in H.M.: that have important implications for assessing six-months recognition, Behav. Neurosci., 102 (1988) anterograde and retrograde amnesia. As such, the 823-827. data are consistent with a component-processes 8 Galef, B.G. Jr., Utilization by Norway rats (R. norvegicus) approach, although, it must be emphasized they of multiple messages concerning distant diets, J. Comp. Psychol., 97 (1983) 364-371. do not permit rejection of an independent-sys- 9 Galef, B.G. Jr. and Wigmore, S.W., Transfer of informa- tems model. Indeed, neither experiment was tion concerning distant food: a laboratory investigationof designed to address this question but the results the 'information-centre' hypothesis, Anim. Behav., 31 do underscore the need to examine the issue with (1983) 748-758. an aim to distinguish between those experimental 10 Graf, P. and Schacter, D.L., Implicit and explicit memory for new associations in normal and amnesic subjects, J. conditions that are likely to lead to memory loss Exp. Psychol.: Learn., Mem. and Cogn., 11 (1985) and those that will support residual memory 501-518. function. 11 Huppert, F.A. and Piercy, M., Normal and abnormal forgetting in organic amnesia, Cortex, 15 (1979) 385-390. 12 Jarrard, L.E., Role of interference in retention by rats ACKNOWLEDGEMENTS with hippocampal lesions, J. Comp. Physiol. Psychol., 89 (1975) 400-408. The present research was supported by a grant 13 Kesner, R.T., Correspondence between humans and animals in coding of temporal attributes: role of hippocam- from the Natural Sciences and Engineering Re- pus and prefrontal cortex, Ann. N.Y. Acad. Sci., 444 search Council of Canada. The help of Bennett G. (1985) 122-136. Galef in developing the test paradigm for this 14 Krnig, J.F.R. and Klippel, R.E, The Rat Brain: A Stereo- research is greatly appreciated. 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