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Spatial memory and hippocampal function
Feuropsycholoqia. g Pcrgmmn Press
Vol. Ltd.
SPATIAL
17. pp. 669 to 682. 1979. Printed in Great
MEMORY
Britain.
AND
HIPPOCAMPAL
FUNCTION
DAVID S. OLTON and BARBARA C. PAPAS Department
of Psychology,
The Johns
Hopkins
(Received
University,
18 April
Baltimore,
hlD 21218,
U.S.A.
1979)
.Abstract-Rats with damage to the fimbria-fornix were tested for the post-operative retention of a preoperatively learned discrimination on a radial arm maze. The maze contained two sets of arms. One set, which never had food on them, comprised the “reference memory” task. The correct response on every approach to each arm in this unbaited set was to refrain from entering it. A second set of arms, each of which had one pellet of food on it at the beginning of a test, comprised the “working memory” task. The correct response to each of the arms in this baited set changed during a test. On the first approach to each of them, the correct response was to run down the arm and obtain the food there; on all subsequent approaches the correct response was to refrain from running down the arm because the food was no longer available. At the end of postoperative testing, performance on the reference memory task was normal, while performance on the working memory task was severely impaired by large lesions and slightly impaired by small ones. Rats with the most complete fimbria-forni.x lesions showed no signs of improvement in working memory. This behavioural dissociation suggests a differential involvement of the hippocampus in working memory as compared to reference memory.
INTRODUCTION A SERIES of experiments
with a radial arm maze have described the characteristics of spatial memory [l-7], a memory based on extramaze [S-IO] but not intramaze stimuli (I, 3, 1 I, 12). Investigations of the neuroanatomical bases of this memory using lesion [13-201, recording [2l] and stimulation [l5,22] techniques have demonstrated a critical role ofthe hippocampus, but not of other brain systems such as the frontal cortex or the caudate nucleus [l5, 181. More detailed experiments with lesions have shown that the impairment of rats with hippocampal system damage in the radial arm maze is not due to response perseveration [ 141, lack of time for stimulus processing [ 161 or the spatial nature of the task [23]. If none of the above account for hippocampal involvement in the task, then the type of memory it requires may be the important variable [ 15, 19, 241. The present experiment tests this hypothesis using a within-subject, within-test design to examine the role of the hippocampal system in two types of memory. One is composed of flexible stimulus-response associations that change from trial to trial and are highly susceptible to interference. The other is composed of fixed stimulus-response associations that remain constant from trial to trial and are relatively immune to interference. These two memory systems will be referred to as a “working memory” and “reference memory”, respectively, following the terminology suggested by HONIG [25]. The experimental design examined only the behavioral dissociation (reference memory vs working memory) following fimbria-fornix lesions. An anatomical dissociation was not attempted because previous experiments have already addressed this issue; destruction of any of the extrinsic connections of the hippocampus (entorhinal area, fimbria-fornix, precomissural fornix or postcommissural fornix) produced a severe and enduring deficit 669
670
DAWD S. OLTON and BARESARAC. PAP.AS
in performance [13, 181, while destruction of the dorsolateral neocortex [13], caudatz nucleus, medial frontal cortex or sulcal frontal cortex [18] did not. Measures ofboth working memory and reference memory were obtained from performance on a 17-arm radial maze. One set of arms, the “baited” set, had one pellet of food at theend of each one at the beginning of each test. The optimal strategy for the rat was to run doivn each of these arms once and only once, thus getting all the food in the minimal number of choices. Performance on the baited set required Lvorking memory because the correct response to each arm changed within a test. On the first approach to an arm, the correct response was to run down it and get the food pellet at the end; on all subsequent approaches the correct response was to refrain from runnin, u dobvn it because food ivas no longer available. Working memory is subject to proactive interference; within each test as the number of arms already chosen by the rat increased, the probability of a correct response (relative to chance) decreased [l-3, 61. The other set of arms, the “unbaited” set, never had food on them. The optimal strategy for the rat on these arms was never to choose them. Performance on the unbaited set can be successful with only reference memory because the correct response to each arm was the same every time the rat approached it. There should be little interference arising in reference memory as a result of previous choices to either the baited or the unbaited arms. If the memory requirement of the usual radial arm maze test is an important dimension influencing the amount of hippocampal involvement, then a behavioral dissociation should appear, with performance on the working memory test impaired and performance on the reference memory test intact. Because all aspects of these two tasks are identical except for the memory requirement, any such dissociation can be confidently attributed to the type of memory required. Rats were given extensive preoperative and postoperative training, and the data analysis was based on terminal, asymptotic postoperative performance. This procedure is advantageous for two reasons. First, it gives the animal with a damaged brain every opportunity to develop the appropriate behavior so that any effects due to changes in motivation, emotionality, or other irrelevant behavioral variables should be minimized [15, 24, 261. Second, permanent or long-term behavioral changes following brain damage than are probably of more significance in makin, ~7inferences about functional localization transitory ones [I 51. METHOD Subjects The subjects were 18 male albino rats, born at Johns Hopkins and derived from a Sprague Dawley strain. At the start of testing, the rats were approximately 90 days old and were housed in individual cages with water continuously available. They were food deprived to 83-y/, of their body weight, with an increase of 5 g per week to allow for normal body growth. The food necessary to maintain them at this weight level was provided approximately I hr after each day’s test. Apparatus The apparatus was a wooden 17-arm 87 cm in diameter and was surrounded guillotine door at the entrance to each equally around the center platform so Further details are presented elsewhere
radial maze elevated 65 cm above the floor. The center platform was by a Masonite wall, 20 cm high, with a hole covered by a metal arm. The arms were 69 cm long and 9 cm wide. and were spaced that the angle between each pair of arms was approximately 21’. [2, 141.
Procedure General. At the beginning of each test, one 190 mg Noyes food pellet was placed in the food cup at the end of each of the eight arms in the baited set. The other nine arms were in the unbaited set; they never
671
!4EMORY AND HIPPOCA.WPAL FUNCTION
contained food. Two patterns of baited arms were used. In the “Adjacent Pattern”, the baited set consisted of eight consecutive arms on one side of the apparatus. In the “iMixed Pattern”. the arms of the baited set were distributed around the maze. The difference in the two patterns may be illustrated by consecutively numbering the arms of the maze in a clockwise direction from 1 to 17. An Adjacent Pattern might have arms l-8 as the baited set. A Mixed Pattern might have arms 1, 2, 6, 9, IO, I I, 14 and 16 as the baited set. Both the Adjacent Pattern and the Mixed Pattern occurred with three different sets of arms in order to control for any possible differences in the ease with which particular arms could be identified or remembered. Each rat was assigned to one of the six sets (two patterns x three locations in the maze). For any given rat, the same set of arms was baited throughout the experiment. Rats tested with the Adjacent Patterns will be called the “Adjacent Group”. Rats tested with the Mixed Patterns will be called the “IMixed Group”. The experimental design and the associated procedures are summarized in Fig. 1.
TYPE
OF
DISCRIMINATION
4 BAITED
UNBAITED
ARMS
ARMS
5
IZ
ONE PELLET OF FOOD ON EICH IRY “WORKING
MEMORY”
NO FOOD ON INI &RM ‘REFERENCE
UEMORY’
ADJACENT
FIG. I. A summary
of the experimental
design.
For further
explanation,
see text.
Acquisition. After shaping [I, 2, 121, rats were tested once a day, 5 days a week. At the beginning of each test, the rat was placed in the center platform with all guillotine doors closed. All the doors were raised simultaneously and the rat allowed to choose an arm. When the rat returned to the center platform, all guillotine doors were lowered, confining him to the center platform for IO sec. Following confinement, all the doors were raised once again. This procedure continued until all eight baited arms had been chosen, or until 15 min had passed. Further details are contained in earlier reports [2, II]. Each rat was given a minimum of30 tests; testing continued (if necessary) until a criterion of a mean 7 correct responses in the first 8choices had been reached for a block of IO consecutive tests. Surgery. Following criterion testing, 4 of the 8 rats Group received electrolytic fimbria-fornix lesions as each group were given sham operations in which all that electrodes were not lowered into the brain. After fornix lesions.
in the Mixed Group and 6 of the 10 rats in the Adjacent described elsewhere [13. 14, 161. The remaining rats in aspects of the surgical procedure were followed except IO postoperative tests, these rats also weregiven Embria-
Posroperafive /aring. Rats given fimbria-fornix lesions in the first operation were given 50 postoperative tests (except for one rat in the Mixed Group who was stopped after 40 tests by mistake). Rats given sham operations were first given IO tests; after the subsequent hmbria-fornix lesions they were given an additional 50 tests. Postoperative testing was identical to that during acquisition, except no shaping was given. Histology. Following the final test period, rats were anesthetized with ether and perfused with0.9%saline followed by IO”/, formalin. The brains were cut in a freezing microtome. Every fourth section, 20 pm thick. was mounted on a slide, stained with 1~x01 fast blue and counter-stained with cresyl violet. An adjacent section, 50 pm thick, was stained for AChE [27, 281. Areas of cell loss, degeneration and gliosis in the sections stained with 1~x01 fast blue and cresyl violet, and the pattern of AChE in the sections stained for AChE were noted and reconstructed on appropriate diagrams of the rat atlas by PELLEGRISO and CUSHVAN [29].
DAVID S. OLTON and
672
B-BAR.\
C. PAPAS
Data were analyzed in blocks of IO days. Performance on the reference memory task vvas measured by the transformed probability of a response to an arm in the baited set, while performance on the working memory task was measured by the transformed probability of a correct response (i.e. a response to an arm in the baited set that still had food), given that the response was to an arm in the baited set. These transformations took into account the level of performance expected by chance on each choice. For the reference memory analysis. the chance probability of a response to an arm in the baited set was taken as the number of arms in this set divided by the total number of arms, or 8 17. For the working memory analysis, the chance probability of a correct response w-as taken as the number of arms in the baited set still containing food divided by 8, the total number of arms in this set. These transformations express performance with scores ranging from I .O to - I .O. A score of 0 indicates chance performance. Positive scores indicate better than chance performance with a score of I .O reflecting a correct response on every choice. Negative scores indicate performance \vorse than that expected by chance. with a score of - I.0 retlecting an incorrect response on every choice. These probabilities were calculated for each of the first S choices in each block of IO tests and then the mean value for all 8 choices was determined, unless otherwise noted. Further details have been provided elsewhere [I]. An important point is that the working memory analysis considered only responses to the set of baited arms. If on a particular choice the rat made a response to an arm in the baited set, the working memory analysis determined the chance probability of a correct response and whether or not the response actually made was correct. If, however. the rat made a response to an arm in the unbaited set, the working memory analysis vvas not carried out. Consequently, the accuracy of choice behavior as determined by the vrorking memory analysis is independent of that determined by the reference memory analysis. Two comparisons of preoperative and postoperative performance were calculated. In A, the mean probability during the last IO postoperative tests was divided by the mean probabilitydurinn thelast IOprcoperative tests. This comparison gives an indication of the extent to which asymptomatic postoperative performance vvas similar to asymptotic preoperative performance. In B, the numerator was the mean probability during the last IO postoperative tests minus the mean probability during the first IO preoperative tests, and the denominator was the mean probability during the last IO preoperative tests minus the mean probability during the first IO preoperative tests. In both comparisons, a score of I .O indicates that terminal postoperative performance was equal to terminal preoperative performance; scores greater than and less than 1.O indicate that terminal postoperative performance was better than and worse than terminal preoperative performance, respectively. In A. a score of 0 indicates that terminal postoperative performance was equal to that expected by chance, while in B a score of 0 indicates that terminal postoperative performance was equal to initial preoperative performance. A Sign test was used for within-subjects comparison, while a Mann-Whitney C/test was used for betweensubjects comparisons [30]. All P values in the text are one-tailed.
RESULTS Preoperative
performance
All rats were shaped to run on the maze without difficulty. During the first 10 preoperative tests, rats performed poorly: the mean probability of a response to an arm of the baited set was 0.22 and 0.62 for the Mixed and Adjacent Groups, respectively, while the mean probability of a correct response for these two groups was 0.71 and 0.57 respectively. Rats rapidly learned the test and reached criterion performance within 30-50 tests. During criterion tests, performance was consistently good and the mean probabilities for rats in the Mixed and Adjacent Groups ranged from 0.86 to 0.98. In the previous experiments usin g the working memory task, the probability of a correct response decreased as the number of choices increased, a result that was taken to indicate interference among items stored in working memory [l-3,6]. The same result was found here for the working memory task, but not for the reference memory task. Figure 3 presents the relevant data from the first 10 days of preoperative testing. The ordinate is the mean probability. A score of 1.00 indicates perfect performance; a score of 0 indicates chance. The abscissa is the number of choices from one to eight. Data from the first choice of the working memory task are not presented, because if the first choice was to an arm in the
MEMORY
I
HIPPOCA.MPAL
AND
a-
MI xEO -
GROUP RESPONSE
o--O
9-
CORRECT
ADJACENT
6-
673
FL-SCTION
TO mH
:N BAITED
SET
RESPONSE
GROUP
H
RESPONSE
TO AilM
iF_-*
CORRECT
RESPONSE
IN BAITED
SET
7-
.2 .I -
I I
! 2
I 3
I
4
I
I
5
6
I
7
J
8
CHOICES
FIG. 2. A comparison of choice accuracy on the reference memory task and the working memory task across choices I-S on the first IO days of preoperative testing. The ordinate presents the transformed mean probability. A score of 0 indicates chance performance: a score . of I .OOindicates perfectly accurate performance.
baited set, it had to be correct. The figure indicates that performance on the working memory task steadily declined as the number of choices increased. For every rat in both groups, the mean probability of a correct response on the last two choices was less than the comparable value on the first two choices (P’s < 0.01). In contrast, performance on the reference memory task did not change significantly across choices. Pet-formance following
sham operations
The cessation of testing and the sham operations had virtually no effect on performance. In fact, the mean probability of choosing an arm in the baited set and the mean probability of a correct response were both slightly higher during the 10 days following sham operations than they were during criterion testing. Histology All rats receiving fimbria-fornix lesions had substantial damage to the fimbria-fornix posterior to the septum and anterior to the hippocampus. The smallest lesions destroyed approximately the medial one-half of the fimbria-fornix bilaterally, while leaving the lateral edges intact. The AChE pattern reflected this damage; the anterodorsal third of the hippocampus was devoid of AChE, while the posteroventral third stained normally; the middle third had some stain, but less than the usual amount. The largest lesions destroyed almost the entire fimbria-fornix, leaving only the most lateral tips intact. In the AChE sections, almost the entire hippocampus was devoid of stain; only the most anteroventral tips of the
671
DAVID
S.
OLTON and
BARBARA
C.
PAPAS
hippocampus, about 5% of its extent, stained postively for AChE. Microphotographs of brains with similar lesions have been published elsewhere [13, 131. Because of the differences in lesion size, the rats in both the hlixed Group and the Adjacent Group were ranked in terms of their lesion size. This ranking was done by three people, two of vvhom knew nothing about the rats’ behavior. For further data analysis, the rats in each Group were divided into two equal subgroups. Rats with “small” lesions vvere the half of each group that had the least damage to the fimbria-fornix, while rats vvith “large” lesions were the half of each group that had the most damage. Postoperative
performance
Both small and lar_ge fimbria-fornix lesions produced a decrease in the mean probability of a response to an arm in the baited set and the mean probability of a correct response for the Mixed Group and the Adjacent Group during the first 10 days of postoperative testing. This decrease was to about the same levels as those observed during the first 10 days of preoperative testing. For all rats, the mean probability of a response to an arm in the baited set increased rapidly, following approximately the same time course as it did preoperatively, until it reached a level similar to that found during terminal preoperative testing. In contrast, the mean probability of a correct response had a postoperative course that was markedly influenced by the size of the lesion. For rats with small lesions, it steadily increased and by the end of postoperative testing was only slightly less than that at the end of preoperative testing. For rats with large lesions, however, it showed little recovery and at the end of postoperative testing \ras substantially lower than at the end of preoperative testing. These data are summarized in Fig. 3, which points out that the only postoperative deficit of substantial magnitude was in the mean probibility of a correct response for rats with large lesions. The results from the two comparisons of preoperative and postoperative performance are summarized in Table I, which presents the mean and the ranges of the values obtained. The mean probability of a response to an arm in the baited set was virtually the same postoperatively as preoperatively (scores were about 1.0) and some rats actually performed
I
.oo r
\0 -
RESPONSE
e--O
CORRECT
TO
ARM
IN
BAITED
RESPONSE’IWORKING
SET:
[REFERENCE
MEMORY1
MEMORY)
01 PRE.
POST
MIXED SMALL
PRE
POST.
ADJACENT LESIONS
PRE
WST
MlXED Lh4GE
PRE
POST
lD.JlCLHT LESIONS
FIG. 3. A summary of performance during the last 10 preoperative tests (‘.Pre”), and the last IO postoperative tests (“Post”) for rats with the Mixed (“Mixed”) or Adjacent (“Adjacent”) Pattern after small (“Small”) or large (“Large”) lesions. The mean probability was taken from the first 8 choices on all 10 tests.
ME.MORY
AND
HIPPOCA.WPAL
FUSCTION
675
676
DAVID
OLTON and BARBMA C. PAPAS
S.
better postoperatively than preoperatively (scores were greater than 1.0). In contrast, the mean probability of a correct response was always less postoperatively than preoperatively, even for rats with small lesions, and especially for rats in the Adjacent Group. Most important, hobvever, was the effect of lesion size. Every rat Lvith a large lesion performed worse than every rat with a small lesion in both the Mixed and Adjacent Groups (P’s < 0.02). Furthermore, taking all rats with large lesions together. all but one rat (in the Mixed Group) on one measure (A) had a lower score for the mean probability of a correct response than for the mean probability of a response to an arm in the baited set (P’s < 0.02). These data demonstrate that large lesions had a greater effect than small lesions on the mean probability of a correct response, and that large lesions had a greater effect on the mean probability of a correct response than on the mean probability of a response to an arm in the baited set. Thus, both lesion size (small vs large) and type of task (working memory vs reference memory) influenced postoperative performance. More detailed analyses were carried out for the rat Lvith the most complete lesion in the Mixed Group and in the Adjacent Group. These data are presented in Figs. 4 and 5, respec-
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43
MIXED I 4
GROUP I 5
I 6
, 7
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CHOICES
FIG. 4. A summary
of the preoperative and postoperative performance of Rat No. 43, the rat with the most complete fimbria-fornix lesion in the Mixed Group.
tively, which show the mean probabilities for each of the first eight choices during the last IO preoperative tests and the last 10 postoperative tests. Preoperatively, both rats performed almost perfectly on all choices, responding only to arms in the baited set that still had food on them. Postoperatively, performance on the reference memory task was virtually the same as it had been preoperatively. Performance on the working memory task, however, was at approximately chance levels. These data indicate that although both these rats were able to identify each of the arms in the unbaited set and inhibit responses to them, they were unable to remember more than one (Rat 43) or two (Rat 48) responses to arms in the baited set and avoid repeating them.
MEMORY
AND HIPPOCAMPAL
677
FC;Z;CTION
76;
.5-
m i
.4-
2
3-
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7
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CHOICES
FIG. 5. A summary of preoperative and postoperative performance for Rat No. 48, the rat with the most complete timbria-fornix lesion in the Adjacent Group.
DISCUSSION The results of this experiment demonstrate a differential involvement of the hippocampal system in reference and working memory. The reference memory task was composed of a set of unbaited arms. These arms never contained food, SO that the optimal strategy for the rat on every approach was to refrain from entering them. Terminal postoperative performance on the reference memory task, as measured by the probability of responding to an arm in the baited set (i.e. avoiding arms in the unbaited set), was unaffected by fimbria-fornix lesions, irrespective of the size of the lesion. The workin g memory task was composed of a set of baited arms. Each of these arms had one pellet of food at its end; the optimal strategy for the rat on the first approach was to run down the arm and obtain the food, and on all subsequent approaches not to run down the arm because the food had been removed. Terminal postoperative performance on the working memory task, as measured by the probability of a correct response given a response to an arm in the baited set, was substantially impaired by large but not by small fimbria-fornix lesions. In fact, the two rats with the most complete lesions performed at approximately chance levels on the working memory task at the end of postoperative testing (while performing almost perfectly on the reference memory task). Thus, we su ggest that the hippocampal system is differentially involved in tasks that require flexible stimulus-response associations or are subject to interference, but not in tasks that can be solved on the basis of fixed stimulus-response associations or are not subject to interference. The precise characteristics of workin g memory that are responsible for this differential involvement cannot be specified in detail. However, there are two obvious differences between the reference and working memory task which seem to be the most likely sources of the observed dissociation. First, the working memory task was composed of variable stimulus-response associations, while the reference memory task was composed of fixed stimulus-response associations. Rats with hippocampal damage are notoriously poor at
678
DAVID
S.
OLTOS and BARBMA
C.
PAP.AS
changing response patterns and exhibiting flexible behavior, while still being able to follow fixed response patterns. For example, they learn without difficulty a continuous reinforcement schedule of bar pressing in which every bar press is rewarded [3l] but exhibit a severe and enduring deficit on a DRL schedule in vvhich they must first press a bar and then inhibit further responding for a set period of time [32]. This DRL deficit appears even vvith minimal preoperative training on a CRF schedule, and with extensive training on a DRL schedule, both preoperatively and postoperatively [32]. Similarly. rats with hippocampal system lesions learn to go to one arm of a T-maze as rapidly as normals. but take many more trials to learn a reversal of this preference [33-361. They also fail to follow a spontaneous alternation pattern [32, 331 or to learn a rewarded alternation pattern [37]. This emphasis on response flexibility [38, 391 is different from that on response inhibition vvhich has often been used to describe the deficit exhibited by rats with hippocampal damage [30-321. In the present experiment, the errors analyzed were alwavs errors ofcommission, responding to an arm when such a response was inappropriate. However, the results demonstrate that response inhibition was intact on the set of arms comprisin g the reference memory test and impaired only on if the deficit is at the the set of arms comprising the workin g memory test. Consequently, response level, it must lie in flexibility rather than inhibition. A second difference between the uorking and reference memory tasks was the amount of interference present as a result of preceding choices, substantial in working memory and minimal in reference memory. The amount of interference has been shown to be important _ _ in the performance of humans with widespread brain damage [a>-101 or hippocampal damage [51, 521 and in rats with hippocampal damage [10, Z-l]. The study by J.\RRARD [23] is particularly important because it assessed the effect of interpolated activity during the intertrial interval on the performance of a rewarded alternation test. Without this interpolated activity, rats with hippocampal system damage performed normally, but with it they performed poorly. This demonstration of the role of interference is particularly strong because it was achieved in a within-subject design. In general, no differences were found in performance with the mixed and adjacent patterns. Because all of the baited arms were next to each other in the adjacent pattern, distinguishing bctrr,celr the arms in the baited set and those in the unbaited set (reference memory) might have been easier than with the mixed pattern, while distinguishing among the arms in the baited set (working memory) might have been more difficult. If such were the case, then rats in the Adjacent Group (as compared to rats in the Mixed Group) ought to have had an increased probability of responding to an arm in the baited set and a decreased probability of making a correct response, both prior to surgery and following fimbriafornix lesions. The only case in which the data supported the above expectations was in performance on the reference memory task during the first 10 preoperative tests. During terminal preoperative testing and terminal postoperative testing, the performance of rats with the adjacent pattern was not significantly different from the performance of rats with the mixed pattern. These results are consistent with others [l-3] suggesting that the spatial distribution of arms around the center platform has relatively little influence on performance on the radial arm maze. Many discussions of hippocampal function have emphasized the impairment of animals with damage to the hippocampal system in spatial [53-581 or cognitive mapping [59-W tasks. The results reported here are not inconsistent with these views, but require an extension of them to include consideration of the type of memory required by the task. Considerable debate has taken place concerning the role of the hippocampus in memory, Particularly
MF&fORYA&D HIPPOCAMPAL FUSCTIOS
679
for animals [69-74. The experiment reported here used a within-subject, within-test design to demonstrate a dissociation of performance on bvorking memory and reference memory tasks. Because all aspects of these tasks were the same except for the memory requirement, factors in common to both of them (such as the type of motivation, the sensory properties of the cues, etc.) cannot be used to explain the observed dissociation. These results provide strong support for the hypothesis presented here, that the critical variable is the type of memory required by the two tasks. rlckno,cleclgenrents-This research was supported in part by Research Grant I-ROI-MH-23213 from the National Institute of Mental Health, and by a Biomedical Sciences Research Grant from The Johns Hopkins University. The authors thank A. BLACK, J. BECKER, G. HANDEL~IANY, L. JARRARD, L. NADEL, S. MITCHELL, J. O’KEEFE, J. RANCH and especially M. MISHKIX for comments on the manuscript, and P. HOLDES, E. KELS~ARTIS and J. KRACH for typing.
REFERENCES of places passed: spatial memory in rats. J. e.rp. I. OLTO~, D. S. and SA>IUELSO>. R. J. Remembrance Psfchol.: Anirnol Behov. Proc. 2, 97-l 16. 1976. in 2. OLTON, D. S., COLLISON, C. and WERZ, M. A. Spatial memory and radial arm maze performance rats. Learn. ,\lotiv. 8, 289-314, 1977. of spatial memory. In Cogrririve Aspects of Animal Eehnvior. S. H. HULSE, 3. OLTOS, D. S. Characteristics W. K. HONIG and H. FOWLER (Editors). pp. 341-373. Lawrence Eribaum, Hillsdale, 1978. 4. OLTOS, D. S., HANOELMANN, G. E. and WALKER, J. A. Spatial memory and food searching strategies. In Foraging Behnvior. A. KA~IIL and T. SERGENT (Editors), Garland STPM Press, New York. In press. OLTOS, D. S. Mazes, maps, and memory. rlfn. Psychol. In press. Ontario, :: ROBERTS, W. A. Some studies of spatial memory in the rat. Can. Psychol. Assn., Ottawa, Canada. 9 June 1978. 7. MAKI, W. S., BROKOFSKY, S. and BERG, S. Spatial memory in rats: Resistance to retroactive interference. Aninr. Lent-n. Behav. In press. 8. ZOLADEK, L. and ROBERTS, W. A. The sensory basis of spatial memory in the rat. Aninr. Learn. Behav. 6, 77-8 I, 1978. 9. BLACK, A. H., AUGERISOS, G. and SUZUKI, S. Stimulus control of behavior on the 8 arm maze. Can. Psychol. Assn., Ottawa, Ontario, Canada, 9 June 1978. IO. SUZ~~KI. S., AU~,ERISOS, G. and BLACK, A. H. Stimulus control ofspatial behavior on theeight arm maze in rats. Learn. ,Lloliv. In press. I I. OLTOS. D. S. and COLLISON. C. Intramaze cues and “odor trails” fail to direct choice behavior on an elevated maze. Atrim. Learn. Behav. In press. I?. W,\LRER, J. A. and OLTOY, D. S. The role of response and reard in spatial memory. Lent-n. Mofiv. In press. 13. OLTON, D. S., WALKER, J. A. and GAGE, F. H. Hippocampal connections and spatial discrimination. Brnin Res. 139, 295-308, 1978. function and behavior: Spatial discrimination and 14. OLTOS, D. S. and WERTZ, M. A. Hippocampal response inhibition. Physiol. Behav. 20, 597-605, 1978. 15. OLTON, D. S. The function of septo-hippocampal connections in spatially organized behaviour. In Fumions of the Sepro-HippoconlpnlSysfetn, Cibn, Fdn Synrp. 58, pp. 327-342. Elsevier, New York, 1978. 16. WALKER, J. A. and OLTON, D. S. Spatial memory deficit following fimbria-fornix lesions: Independent of time for stimulus processing. Physiol. Behov. In press. 17. HA~DELLIANN, G. E., COYLE, J. T. and OLTON, D. S. Lesions of CA3 pyramidal cells with kainic acid impairs spatial memory in rats. Sociery for Neuroscience, 8th Anneal Meefing 4, 221, 1978 (Abstract). IS. BECKER, J. T., WALKER, J. A., OLTON, D. S. and O’CONNELL. B. C. Neuroanatomical bases of shortterm spatial memory in the rat. Sociery for IVerrroscience, 8tl1 Annrm[ Meeting 4. 73, 1978 (Abstract). 19. JARRARD, L. E. Hippocampal lesions and spatial discrimination. J. camp. Phgsiol. Psychol. In press. 20. JARRARD. L. E. Selective hippocampal lesions and spatial discrimination in the rat. Society for iVewoscience, 8th Anrwal
680
DAVID S. OLTON and BARBARA C. PAPAS
24. JARRARD, L. E. Role of interference in retention by rats with hippocampal lesions. J. camp. Physiol. 89,4OQ--tO8, 1975. 25. HONIG, W. K. Studies of working memory in the pigeon. In Cognitive rlspecrs of Animal Behaviour. S. H. HCLSE. W. K. HOSIG and H. FOWLER (Editors), pp. 21 l-248. Lawrence Eribaum Associates, Hillsdale, 1978. 26. NORCIAN, D. A. What have animal experiments taught us about human memory? In The Physiological Basis of .Wemory. J. A. DEUTSCH (Editor). Academic Press, New York, 1973. 27. LYSCH, G., MATTHEWS, D. A., MOSKO, S., PARKS, T. and COTSIAN, C. W. Induced acetylcholinesteraserich layer in dentate rat dentate gyrus following entorhinal lesions. Bruin Res. 42, 31 l-318, 1972. 28. LYSCH, G. and COTUAN, C. W. The hippocampus as a model for studying anatomical plasticity in the adult brain. In The Hippocumpra, R. L. ISAACSON and K. H. PRIBR.A.M(Editors), Vol. 1. pp. 123-154. Plenum Press, New York, 1973. 29. PELLEGRISO, L. J. and CUSHMAN, A. H. A Stereotuxic AIIUS of rhe Rut Bruin. Appleton-Century-Crofts, New York, 1967. 30. SIEGEL, S. ~Vonporumerric Srufisrics for rhe Behavioral Sciences. %lcGraw-Hill, New York, 1956. 31. SCH~~ALTZ. L. W. and ISSACSON, R. L. The effects of preliminary training conditions upon DRL performance in the hippocampectomized rat. Physiol. Behav. 1, 175-182, 1966. 32. JOHNSOS, C. T., OLTOS, D. S., GAGE, F. H. III and JENKO, P. G. Damage to hippocampus and hippocampai connections: Effects on DRL and spontaneous alternation. J. contp. Physiol. Pswhol. 91, 508522, 1977. 33. DOUGLAS, R. J. The hippocampus and behavior. Psychol. Bul/. 416-442, 1967. 34. GREENE, E. and STAUFF, C. Behavioral role of hippocampal connections. Ex~. Nellrol. 45,141-160, 1953. 35. JARRARD, L. E. Anatomical and behavioral analysis of hippocampal cell fields in rats. J. camp. Physiol. Psychol. 90, 1035-1050, 1976. 36. KI.MBLE, D. P. The effects of bilateral hippocampal lesions in rats. J. camp. Physiol. Psychol. 56,273-283, 1963. 37. SINNAMON, H. M., FRENIERE, S. and KOOTZ, J. Rat hippocampus and memory for places of changing significance. J. camp. Physiol. PsychoI. 92, 112-155, 1978. 38. OLTON, D. S. Behavioral and neuroanatomical differentiation of response-shift and response-suppression mechanisms in the rat. J. camp. Physiol. Psychol. 78, 450456, 1977. 39. HIRSCH, R. Lack of variability or preservation: Describing the effect of hippocampal ablation. Physiol. Behuv. 5, 1249-l 254. 1970. 40. ALTMAN, J., BRUNNER, R. L. and BAYER, S. A. The hippocampus and behavioral maturation. Behuv. Biol. 8, 557-596. 1973. 41. ISAACSON, R. L. The Limbic System. Plenum, New York, 1974. 42. KI.~BLE, D. P. Hippocampus and internal inhibition. Psychol. 81111.00, 285-295, 1968. retention with special 43. WARRISGTON, E. K. and WEISKRANTZ, L. A new method of testing long-term reference to amnesic patients. Nucflre, Lond. 217, 972-974, 1968. 44. WARRIPL;GTOS, E. K. and WEISKRANTZ, L. Organizational aspects of memory in amnesic patients. Nerrropsychologiu 9, 67-73. 197 I 45. WARRINGTOX, E. K. and WEISKRANTZ, L. The effect of prior learning on subsequent retention in amnesic patients. Newopsychologiu 12, 419-428, 1974. 46 WEISKRANTZ, L. A comparison of hippocampal pathology in man and other animals. In Flirnctjons of the Sepro-Hippocumpul System, Cibu Fdn Symp. 58, 373-387. Elsevier, New York, 1978. 47. WEISKRANTZ. L. and WARRINGTON, E. K. Verbal learning and retention by amnesic patients using partial information. Psychon. Sri. 20, 210-21 I, 1970. 48. WEISKRANTZ, L. and WARRINGTON, E. K. A study of forgetting in amnesic patients. Neuropsychologiu 8, 281-288, 1970. in man and animals. 49. WEISKRAXTZ, L. and WARRINGTON, E. K. The problem of the amnesic syndrome In The Hippocumplls. R. L. ISAACSON and K. H. PRIBRA.M (Editors), Vol. 2, pp. 41 l-428. Plenum Press, New York. of paired-associate learning in amnestic patients. 50. WINOCUR, B. and WEISKRANTZ, L. An investigation Nertropsychologiu 14, 97-l IO, 1976. 51. MILNER, B. Preface: Material specific and generalized learning loss. Neuropsychologia 6, 175-179, 1968 52. MILNER, B., CORKIN, S. and TEUBER, H.-L. Further analysis of hippocampal amnesic syndrome: A 14 year follow-up study of H.M. Newopsychologiu 6, 215-234, 1968. lobe ablation. Neuro53. MAHUT, H. Spatial and object reversal learning in monkeys with partial temporal wychologiu 9, 409-429, I97 I. 54. MAHUT. H. A selective spatial deficit in monkeys after transection of the fornix. Netrropsychofogiu 10, 55-74. 1972. specific impairment in spatial learning after fornix lesions 55. MAHUT, H. and ZOLA, S. M. A nonmodality n monkeys. Neuropsychologiu It, 225-269, 1973.
%tE.LIORY AND HIPPOCAMPAL FC’NCTION
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56. DECASTRO, J. M. A selective spatial discrimination deficit after fornicotomy in the rat. Behav. Bioi. 12, 373-382.1974. 57. ZOLA, S. M. and MAHUT, H. Paradoxical facilitation of object reversal learning after transection of the fornix in monkeys. Nerrropsycholugiu 11, 172-l 84, 1973. 58. JOSES, B. and MISHKIN, M. Limbic lesions and the problem of stimulus-reinforcement associations. frp. ‘Veurol. 36, 362-277, 1972. 59. O’KEEFE, J. and DOSTROVSKY, J. The hippocampus as a cognitive map. Preliminary evidence from unit activity in freely moving rat. Brain Res. 34, 171-175, 1971. 60. O’KEEFE, J. Place units in the hippocampus of the freely moving rat. Exp. 1Veurol. 51, 78-109, 1976. 61. O’KEEFE, J. and BLACK, A. H. Single unit and lesion experiments on the sensory inputs to the hippocampal cognitive map. In Functions of rhe Septo-Hippocampal Sysrem, Ciba Fdn Sytnp. 58, 179-192. Elsevier. New York, 1978. 62. O’KEEFE, J. and CONWAY, D. H. Hippocampal place units: Why they fire where they fire. Erp. Brain Res. 31, 573-590, 1978. 63. NADEL, L., O’KEEFE, J. and BLACK, A. Slam on the brades: A critique of Altman, Brunner, and Bayer’s response-inhibition model of hippocampal function. Behav. Biol. 14, 151-162, 1975. 64. BLACK, A. H., NADEL, L. and O’KEEFE, J. Hippocampal function in avoidance learning and punishment. Psychal. 8~11.84, 1107-l 129, 1977. 65. BLACK, A. H. Hippocampal electrical activity and behavior. In The Hippocampus. R. L. ISAACSON and K. H. PRIBRA.M(Editors), Vol. 2, pp. 129-l 67. Plenum Press, New York. 1975. 66. O’KEEFE, J. and NADEL, L. 7Xe Hippocampus as a Cognitive Mop. Oxford University Press, London, 1978. 67. NADEL, L. and O’KEEFE, J. The hippocampus in pieces and patches: An essay on modes of explanation in psychological psychology. In Essays on rhe Nervous System. A Fesrschriff for Prof. J. Z. Young. R. BELLAIRS and E. G. GRAY (Editors). Clarendon Press, Oxford, 1974. 68. O’KEEFE. J., NADEL, L., KEIGHTLY, S. and KILL, D. Fornix lesions selectively abolish place learning in the rat. Exp. Neural. 48, 152-166, 1975. 69. HOREL, J. A. The neuroanatomy of amnesia. Brain 101,403145, 1978. 70. IVERSEN, S. D. Do hippocampal lesions produce amnesia in animals? In/. Rev. Newobiol. 19, 1119, 1976. 7 I. BERCER, T. W.. ALGER, B. E. and THO~~PSON, R. F. Neuronal substrates of classical conditioning in the hippocampus. Science, N. Y. 192,483-485, 1976. 72. SEGAL. M., DISTERHOFT, J. F. and OLDS, J. Hippocampal unit activity during classical aversive and appetitive conditioning. Science, N. Y. 175, 792-794, 1972. 73. THOMPSON, R. F. The search for the engram. Am. Psychol. 31, 209-227, 1976. 74. OLD?., J. Learning and the hippocampus. Rev. Can. Biol. 31, 215-238, 1972. :
Rdsum6
On
a
teste des rats
sur la retention .4 branches
radlales
tait
2 series
mais
de nourriture
La reponse
avec
post-op6ratoire apprise
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dans
cette
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de ne pas y p&nGtrer.
chacune
wait
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dans
la r6ponse
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correcte
etait
les petite*
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les ap-
les grandes
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Chez
de
“memoire
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les rats
on ne constatait
de travail".
et dans
de reference"
sur la tkhe
par
implication
de travail"
de par-
A toutes
A la fin du test post-opera-
complSte*,
la "memoire
de*
de ne pas y penetrer
de "m&moire
perturb&es
les plus dans
la "m&moire
a chacune
A la premiere
les performances
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de nourriture.
que
de nourriture
du test.
sur la tache
tandis
3 chaque
de branches
au tours
obtenir
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changeait
des branches,
les performances
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signe
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n'y avait
toute
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on ne mettait
de "memoire
second
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682
D.AVID S. OLTON
Deutschsprachige Ratten
Zusaxmenfassung:
nit Schadigung
postoperative
and BARBARA C. PAPAS
der Fimbriae
Gedachtnis
krininationsnuster
getestet.
eines strahlenfdrmigen
des Fornix wurden
fiir ein praoperativ ZS
muf3te die raumliche
Irrgartens
behalten
setzte sich aus zwei Arten von GBngen hielt nienals Gedachtnis bestand
Futter,
werden.
zusanmen.
Das richtige
Verhalten
Eine zweite Anordnung
weils bei Testbeginn
fitter enthielt,
dachtnis
Das korrekte
betrachtet.
GBnge in diesem Bercich wechselte
Einer davon ent-
bei jeden Versuch
wUhrend
die korrekte
in jedem dieser
des Testversuchs.
bestand
in dem sich das fitter befand.
fen,weil.nun
war es korrekt,
das Futter nicht nehr
Ende der Untersuchung,
sionen
Verhalten Weise
ist.
unbeeintrachtigt
zu lau-
spricht
erwies
geblie-
bei ausgedehnten
hatte, bei leichteren
campus
in verschiedener
In allen
nicht dorthin
das "working"-Gedachtnis
stark gelitten
darin, in
nach Durchfiihrung der Operation,
Dieses unterschiedliche bezogen
Antwort
zur Verfiigung stand. Bei
sich, da0 das "reference"-Gedachtnis ben war, wghrend
die je-
w-urde als "working"-Ge-
Verhalten
Beim ersten Versuch
Versuchen
Bereich
von Gsngen,
den Gang zu laufen, nachfolgenden
Verteilung Der irrgarten
in diesen nicht mit Futter versehenen
nicht einzutreten.
Dis-
er wurde als Test fiir tin "referencetl-
angesehen.
darin,
auf das
erlerntes
Schaden
La-
geringer.
dafiir, clal3dcr Hippe-
in die Gedachtnisfunktionen
ein-
Vol. Ltd.
SPATIAL
17. pp. 669 to 682. 1979. Printed in Great
MEMORY
Britain.
AND
HIPPOCAMPAL
FUNCTION
DAVID S. OLTON and BARBARA C. PAPAS Department
of Psychology,
The Johns
Hopkins
(Received
University,
18 April
Baltimore,
hlD 21218,
U.S.A.
1979)
.Abstract-Rats with damage to the fimbria-fornix were tested for the post-operative retention of a preoperatively learned discrimination on a radial arm maze. The maze contained two sets of arms. One set, which never had food on them, comprised the “reference memory” task. The correct response on every approach to each arm in this unbaited set was to refrain from entering it. A second set of arms, each of which had one pellet of food on it at the beginning of a test, comprised the “working memory” task. The correct response to each of the arms in this baited set changed during a test. On the first approach to each of them, the correct response was to run down the arm and obtain the food there; on all subsequent approaches the correct response was to refrain from running down the arm because the food was no longer available. At the end of postoperative testing, performance on the reference memory task was normal, while performance on the working memory task was severely impaired by large lesions and slightly impaired by small ones. Rats with the most complete fimbria-forni.x lesions showed no signs of improvement in working memory. This behavioural dissociation suggests a differential involvement of the hippocampus in working memory as compared to reference memory.
INTRODUCTION A SERIES of experiments
with a radial arm maze have described the characteristics of spatial memory [l-7], a memory based on extramaze [S-IO] but not intramaze stimuli (I, 3, 1 I, 12). Investigations of the neuroanatomical bases of this memory using lesion [13-201, recording [2l] and stimulation [l5,22] techniques have demonstrated a critical role ofthe hippocampus, but not of other brain systems such as the frontal cortex or the caudate nucleus [l5, 181. More detailed experiments with lesions have shown that the impairment of rats with hippocampal system damage in the radial arm maze is not due to response perseveration [ 141, lack of time for stimulus processing [ 161 or the spatial nature of the task [23]. If none of the above account for hippocampal involvement in the task, then the type of memory it requires may be the important variable [ 15, 19, 241. The present experiment tests this hypothesis using a within-subject, within-test design to examine the role of the hippocampal system in two types of memory. One is composed of flexible stimulus-response associations that change from trial to trial and are highly susceptible to interference. The other is composed of fixed stimulus-response associations that remain constant from trial to trial and are relatively immune to interference. These two memory systems will be referred to as a “working memory” and “reference memory”, respectively, following the terminology suggested by HONIG [25]. The experimental design examined only the behavioral dissociation (reference memory vs working memory) following fimbria-fornix lesions. An anatomical dissociation was not attempted because previous experiments have already addressed this issue; destruction of any of the extrinsic connections of the hippocampus (entorhinal area, fimbria-fornix, precomissural fornix or postcommissural fornix) produced a severe and enduring deficit 669
670
DAWD S. OLTON and BARESARAC. PAP.AS
in performance [13, 181, while destruction of the dorsolateral neocortex [13], caudatz nucleus, medial frontal cortex or sulcal frontal cortex [18] did not. Measures ofboth working memory and reference memory were obtained from performance on a 17-arm radial maze. One set of arms, the “baited” set, had one pellet of food at theend of each one at the beginning of each test. The optimal strategy for the rat was to run doivn each of these arms once and only once, thus getting all the food in the minimal number of choices. Performance on the baited set required Lvorking memory because the correct response to each arm changed within a test. On the first approach to an arm, the correct response was to run down it and get the food pellet at the end; on all subsequent approaches the correct response was to refrain from runnin, u dobvn it because food ivas no longer available. Working memory is subject to proactive interference; within each test as the number of arms already chosen by the rat increased, the probability of a correct response (relative to chance) decreased [l-3, 61. The other set of arms, the “unbaited” set, never had food on them. The optimal strategy for the rat on these arms was never to choose them. Performance on the unbaited set can be successful with only reference memory because the correct response to each arm was the same every time the rat approached it. There should be little interference arising in reference memory as a result of previous choices to either the baited or the unbaited arms. If the memory requirement of the usual radial arm maze test is an important dimension influencing the amount of hippocampal involvement, then a behavioral dissociation should appear, with performance on the working memory test impaired and performance on the reference memory test intact. Because all aspects of these two tasks are identical except for the memory requirement, any such dissociation can be confidently attributed to the type of memory required. Rats were given extensive preoperative and postoperative training, and the data analysis was based on terminal, asymptotic postoperative performance. This procedure is advantageous for two reasons. First, it gives the animal with a damaged brain every opportunity to develop the appropriate behavior so that any effects due to changes in motivation, emotionality, or other irrelevant behavioral variables should be minimized [15, 24, 261. Second, permanent or long-term behavioral changes following brain damage than are probably of more significance in makin, ~7inferences about functional localization transitory ones [I 51. METHOD Subjects The subjects were 18 male albino rats, born at Johns Hopkins and derived from a Sprague Dawley strain. At the start of testing, the rats were approximately 90 days old and were housed in individual cages with water continuously available. They were food deprived to 83-y/, of their body weight, with an increase of 5 g per week to allow for normal body growth. The food necessary to maintain them at this weight level was provided approximately I hr after each day’s test. Apparatus The apparatus was a wooden 17-arm 87 cm in diameter and was surrounded guillotine door at the entrance to each equally around the center platform so Further details are presented elsewhere
radial maze elevated 65 cm above the floor. The center platform was by a Masonite wall, 20 cm high, with a hole covered by a metal arm. The arms were 69 cm long and 9 cm wide. and were spaced that the angle between each pair of arms was approximately 21’. [2, 141.
Procedure General. At the beginning of each test, one 190 mg Noyes food pellet was placed in the food cup at the end of each of the eight arms in the baited set. The other nine arms were in the unbaited set; they never
671
!4EMORY AND HIPPOCA.WPAL FUNCTION
contained food. Two patterns of baited arms were used. In the “Adjacent Pattern”, the baited set consisted of eight consecutive arms on one side of the apparatus. In the “iMixed Pattern”. the arms of the baited set were distributed around the maze. The difference in the two patterns may be illustrated by consecutively numbering the arms of the maze in a clockwise direction from 1 to 17. An Adjacent Pattern might have arms l-8 as the baited set. A Mixed Pattern might have arms 1, 2, 6, 9, IO, I I, 14 and 16 as the baited set. Both the Adjacent Pattern and the Mixed Pattern occurred with three different sets of arms in order to control for any possible differences in the ease with which particular arms could be identified or remembered. Each rat was assigned to one of the six sets (two patterns x three locations in the maze). For any given rat, the same set of arms was baited throughout the experiment. Rats tested with the Adjacent Patterns will be called the “Adjacent Group”. Rats tested with the Mixed Patterns will be called the “IMixed Group”. The experimental design and the associated procedures are summarized in Fig. 1.
TYPE
OF
DISCRIMINATION
4 BAITED
UNBAITED
ARMS
ARMS
5
IZ
ONE PELLET OF FOOD ON EICH IRY “WORKING
MEMORY”
NO FOOD ON INI &RM ‘REFERENCE
UEMORY’
ADJACENT
FIG. I. A summary
of the experimental
design.
For further
explanation,
see text.
Acquisition. After shaping [I, 2, 121, rats were tested once a day, 5 days a week. At the beginning of each test, the rat was placed in the center platform with all guillotine doors closed. All the doors were raised simultaneously and the rat allowed to choose an arm. When the rat returned to the center platform, all guillotine doors were lowered, confining him to the center platform for IO sec. Following confinement, all the doors were raised once again. This procedure continued until all eight baited arms had been chosen, or until 15 min had passed. Further details are contained in earlier reports [2, II]. Each rat was given a minimum of30 tests; testing continued (if necessary) until a criterion of a mean 7 correct responses in the first 8choices had been reached for a block of IO consecutive tests. Surgery. Following criterion testing, 4 of the 8 rats Group received electrolytic fimbria-fornix lesions as each group were given sham operations in which all that electrodes were not lowered into the brain. After fornix lesions.
in the Mixed Group and 6 of the 10 rats in the Adjacent described elsewhere [13. 14, 161. The remaining rats in aspects of the surgical procedure were followed except IO postoperative tests, these rats also weregiven Embria-
Posroperafive /aring. Rats given fimbria-fornix lesions in the first operation were given 50 postoperative tests (except for one rat in the Mixed Group who was stopped after 40 tests by mistake). Rats given sham operations were first given IO tests; after the subsequent hmbria-fornix lesions they were given an additional 50 tests. Postoperative testing was identical to that during acquisition, except no shaping was given. Histology. Following the final test period, rats were anesthetized with ether and perfused with0.9%saline followed by IO”/, formalin. The brains were cut in a freezing microtome. Every fourth section, 20 pm thick. was mounted on a slide, stained with 1~x01 fast blue and counter-stained with cresyl violet. An adjacent section, 50 pm thick, was stained for AChE [27, 281. Areas of cell loss, degeneration and gliosis in the sections stained with 1~x01 fast blue and cresyl violet, and the pattern of AChE in the sections stained for AChE were noted and reconstructed on appropriate diagrams of the rat atlas by PELLEGRISO and CUSHVAN [29].
DAVID S. OLTON and
672
B-BAR.\
C. PAPAS
Data were analyzed in blocks of IO days. Performance on the reference memory task vvas measured by the transformed probability of a response to an arm in the baited set, while performance on the working memory task was measured by the transformed probability of a correct response (i.e. a response to an arm in the baited set that still had food), given that the response was to an arm in the baited set. These transformations took into account the level of performance expected by chance on each choice. For the reference memory analysis. the chance probability of a response to an arm in the baited set was taken as the number of arms in this set divided by the total number of arms, or 8 17. For the working memory analysis, the chance probability of a correct response w-as taken as the number of arms in the baited set still containing food divided by 8, the total number of arms in this set. These transformations express performance with scores ranging from I .O to - I .O. A score of 0 indicates chance performance. Positive scores indicate better than chance performance with a score of I .O reflecting a correct response on every choice. Negative scores indicate performance \vorse than that expected by chance. with a score of - I.0 retlecting an incorrect response on every choice. These probabilities were calculated for each of the first S choices in each block of IO tests and then the mean value for all 8 choices was determined, unless otherwise noted. Further details have been provided elsewhere [I]. An important point is that the working memory analysis considered only responses to the set of baited arms. If on a particular choice the rat made a response to an arm in the baited set, the working memory analysis determined the chance probability of a correct response and whether or not the response actually made was correct. If, however. the rat made a response to an arm in the unbaited set, the working memory analysis vvas not carried out. Consequently, the accuracy of choice behavior as determined by the vrorking memory analysis is independent of that determined by the reference memory analysis. Two comparisons of preoperative and postoperative performance were calculated. In A, the mean probability during the last IO postoperative tests was divided by the mean probabilitydurinn thelast IOprcoperative tests. This comparison gives an indication of the extent to which asymptomatic postoperative performance vvas similar to asymptotic preoperative performance. In B, the numerator was the mean probability during the last IO postoperative tests minus the mean probability during the first IO preoperative tests, and the denominator was the mean probability during the last IO preoperative tests minus the mean probability during the first IO preoperative tests. In both comparisons, a score of I .O indicates that terminal postoperative performance was equal to terminal preoperative performance; scores greater than and less than 1.O indicate that terminal postoperative performance was better than and worse than terminal preoperative performance, respectively. In A. a score of 0 indicates that terminal postoperative performance was equal to that expected by chance, while in B a score of 0 indicates that terminal postoperative performance was equal to initial preoperative performance. A Sign test was used for within-subjects comparison, while a Mann-Whitney C/test was used for betweensubjects comparisons [30]. All P values in the text are one-tailed.
RESULTS Preoperative
performance
All rats were shaped to run on the maze without difficulty. During the first 10 preoperative tests, rats performed poorly: the mean probability of a response to an arm of the baited set was 0.22 and 0.62 for the Mixed and Adjacent Groups, respectively, while the mean probability of a correct response for these two groups was 0.71 and 0.57 respectively. Rats rapidly learned the test and reached criterion performance within 30-50 tests. During criterion tests, performance was consistently good and the mean probabilities for rats in the Mixed and Adjacent Groups ranged from 0.86 to 0.98. In the previous experiments usin g the working memory task, the probability of a correct response decreased as the number of choices increased, a result that was taken to indicate interference among items stored in working memory [l-3,6]. The same result was found here for the working memory task, but not for the reference memory task. Figure 3 presents the relevant data from the first 10 days of preoperative testing. The ordinate is the mean probability. A score of 1.00 indicates perfect performance; a score of 0 indicates chance. The abscissa is the number of choices from one to eight. Data from the first choice of the working memory task are not presented, because if the first choice was to an arm in the
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FIG. 2. A comparison of choice accuracy on the reference memory task and the working memory task across choices I-S on the first IO days of preoperative testing. The ordinate presents the transformed mean probability. A score of 0 indicates chance performance: a score . of I .OOindicates perfectly accurate performance.
baited set, it had to be correct. The figure indicates that performance on the working memory task steadily declined as the number of choices increased. For every rat in both groups, the mean probability of a correct response on the last two choices was less than the comparable value on the first two choices (P’s < 0.01). In contrast, performance on the reference memory task did not change significantly across choices. Pet-formance following
sham operations
The cessation of testing and the sham operations had virtually no effect on performance. In fact, the mean probability of choosing an arm in the baited set and the mean probability of a correct response were both slightly higher during the 10 days following sham operations than they were during criterion testing. Histology All rats receiving fimbria-fornix lesions had substantial damage to the fimbria-fornix posterior to the septum and anterior to the hippocampus. The smallest lesions destroyed approximately the medial one-half of the fimbria-fornix bilaterally, while leaving the lateral edges intact. The AChE pattern reflected this damage; the anterodorsal third of the hippocampus was devoid of AChE, while the posteroventral third stained normally; the middle third had some stain, but less than the usual amount. The largest lesions destroyed almost the entire fimbria-fornix, leaving only the most lateral tips intact. In the AChE sections, almost the entire hippocampus was devoid of stain; only the most anteroventral tips of the
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hippocampus, about 5% of its extent, stained postively for AChE. Microphotographs of brains with similar lesions have been published elsewhere [13, 131. Because of the differences in lesion size, the rats in both the hlixed Group and the Adjacent Group were ranked in terms of their lesion size. This ranking was done by three people, two of vvhom knew nothing about the rats’ behavior. For further data analysis, the rats in each Group were divided into two equal subgroups. Rats with “small” lesions vvere the half of each group that had the least damage to the fimbria-fornix, while rats vvith “large” lesions were the half of each group that had the most damage. Postoperative
performance
Both small and lar_ge fimbria-fornix lesions produced a decrease in the mean probability of a response to an arm in the baited set and the mean probability of a correct response for the Mixed Group and the Adjacent Group during the first 10 days of postoperative testing. This decrease was to about the same levels as those observed during the first 10 days of preoperative testing. For all rats, the mean probability of a response to an arm in the baited set increased rapidly, following approximately the same time course as it did preoperatively, until it reached a level similar to that found during terminal preoperative testing. In contrast, the mean probability of a correct response had a postoperative course that was markedly influenced by the size of the lesion. For rats with small lesions, it steadily increased and by the end of postoperative testing was only slightly less than that at the end of preoperative testing. For rats with large lesions, however, it showed little recovery and at the end of postoperative testing \ras substantially lower than at the end of preoperative testing. These data are summarized in Fig. 3, which points out that the only postoperative deficit of substantial magnitude was in the mean probibility of a correct response for rats with large lesions. The results from the two comparisons of preoperative and postoperative performance are summarized in Table I, which presents the mean and the ranges of the values obtained. The mean probability of a response to an arm in the baited set was virtually the same postoperatively as preoperatively (scores were about 1.0) and some rats actually performed
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FIG. 3. A summary of performance during the last 10 preoperative tests (‘.Pre”), and the last IO postoperative tests (“Post”) for rats with the Mixed (“Mixed”) or Adjacent (“Adjacent”) Pattern after small (“Small”) or large (“Large”) lesions. The mean probability was taken from the first 8 choices on all 10 tests.
ME.MORY
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S.
better postoperatively than preoperatively (scores were greater than 1.0). In contrast, the mean probability of a correct response was always less postoperatively than preoperatively, even for rats with small lesions, and especially for rats in the Adjacent Group. Most important, hobvever, was the effect of lesion size. Every rat Lvith a large lesion performed worse than every rat with a small lesion in both the Mixed and Adjacent Groups (P’s < 0.02). Furthermore, taking all rats with large lesions together. all but one rat (in the Mixed Group) on one measure (A) had a lower score for the mean probability of a correct response than for the mean probability of a response to an arm in the baited set (P’s < 0.02). These data demonstrate that large lesions had a greater effect than small lesions on the mean probability of a correct response, and that large lesions had a greater effect on the mean probability of a correct response than on the mean probability of a response to an arm in the baited set. Thus, both lesion size (small vs large) and type of task (working memory vs reference memory) influenced postoperative performance. More detailed analyses were carried out for the rat Lvith the most complete lesion in the Mixed Group and in the Adjacent Group. These data are presented in Figs. 4 and 5, respec-
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FIG. 4. A summary
of the preoperative and postoperative performance of Rat No. 43, the rat with the most complete fimbria-fornix lesion in the Mixed Group.
tively, which show the mean probabilities for each of the first eight choices during the last IO preoperative tests and the last 10 postoperative tests. Preoperatively, both rats performed almost perfectly on all choices, responding only to arms in the baited set that still had food on them. Postoperatively, performance on the reference memory task was virtually the same as it had been preoperatively. Performance on the working memory task, however, was at approximately chance levels. These data indicate that although both these rats were able to identify each of the arms in the unbaited set and inhibit responses to them, they were unable to remember more than one (Rat 43) or two (Rat 48) responses to arms in the baited set and avoid repeating them.
MEMORY
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FIG. 5. A summary of preoperative and postoperative performance for Rat No. 48, the rat with the most complete timbria-fornix lesion in the Adjacent Group.
DISCUSSION The results of this experiment demonstrate a differential involvement of the hippocampal system in reference and working memory. The reference memory task was composed of a set of unbaited arms. These arms never contained food, SO that the optimal strategy for the rat on every approach was to refrain from entering them. Terminal postoperative performance on the reference memory task, as measured by the probability of responding to an arm in the baited set (i.e. avoiding arms in the unbaited set), was unaffected by fimbria-fornix lesions, irrespective of the size of the lesion. The workin g memory task was composed of a set of baited arms. Each of these arms had one pellet of food at its end; the optimal strategy for the rat on the first approach was to run down the arm and obtain the food, and on all subsequent approaches not to run down the arm because the food had been removed. Terminal postoperative performance on the working memory task, as measured by the probability of a correct response given a response to an arm in the baited set, was substantially impaired by large but not by small fimbria-fornix lesions. In fact, the two rats with the most complete lesions performed at approximately chance levels on the working memory task at the end of postoperative testing (while performing almost perfectly on the reference memory task). Thus, we su ggest that the hippocampal system is differentially involved in tasks that require flexible stimulus-response associations or are subject to interference, but not in tasks that can be solved on the basis of fixed stimulus-response associations or are not subject to interference. The precise characteristics of workin g memory that are responsible for this differential involvement cannot be specified in detail. However, there are two obvious differences between the reference and working memory task which seem to be the most likely sources of the observed dissociation. First, the working memory task was composed of variable stimulus-response associations, while the reference memory task was composed of fixed stimulus-response associations. Rats with hippocampal damage are notoriously poor at
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OLTOS and BARBMA
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PAP.AS
changing response patterns and exhibiting flexible behavior, while still being able to follow fixed response patterns. For example, they learn without difficulty a continuous reinforcement schedule of bar pressing in which every bar press is rewarded [3l] but exhibit a severe and enduring deficit on a DRL schedule in vvhich they must first press a bar and then inhibit further responding for a set period of time [32]. This DRL deficit appears even vvith minimal preoperative training on a CRF schedule, and with extensive training on a DRL schedule, both preoperatively and postoperatively [32]. Similarly. rats with hippocampal system lesions learn to go to one arm of a T-maze as rapidly as normals. but take many more trials to learn a reversal of this preference [33-361. They also fail to follow a spontaneous alternation pattern [32, 331 or to learn a rewarded alternation pattern [37]. This emphasis on response flexibility [38, 391 is different from that on response inhibition vvhich has often been used to describe the deficit exhibited by rats with hippocampal damage [30-321. In the present experiment, the errors analyzed were alwavs errors ofcommission, responding to an arm when such a response was inappropriate. However, the results demonstrate that response inhibition was intact on the set of arms comprisin g the reference memory test and impaired only on if the deficit is at the the set of arms comprising the workin g memory test. Consequently, response level, it must lie in flexibility rather than inhibition. A second difference between the uorking and reference memory tasks was the amount of interference present as a result of preceding choices, substantial in working memory and minimal in reference memory. The amount of interference has been shown to be important _ _ in the performance of humans with widespread brain damage [a>-101 or hippocampal damage [51, 521 and in rats with hippocampal damage [10, Z-l]. The study by J.\RRARD [23] is particularly important because it assessed the effect of interpolated activity during the intertrial interval on the performance of a rewarded alternation test. Without this interpolated activity, rats with hippocampal system damage performed normally, but with it they performed poorly. This demonstration of the role of interference is particularly strong because it was achieved in a within-subject design. In general, no differences were found in performance with the mixed and adjacent patterns. Because all of the baited arms were next to each other in the adjacent pattern, distinguishing bctrr,celr the arms in the baited set and those in the unbaited set (reference memory) might have been easier than with the mixed pattern, while distinguishing among the arms in the baited set (working memory) might have been more difficult. If such were the case, then rats in the Adjacent Group (as compared to rats in the Mixed Group) ought to have had an increased probability of responding to an arm in the baited set and a decreased probability of making a correct response, both prior to surgery and following fimbriafornix lesions. The only case in which the data supported the above expectations was in performance on the reference memory task during the first 10 preoperative tests. During terminal preoperative testing and terminal postoperative testing, the performance of rats with the adjacent pattern was not significantly different from the performance of rats with the mixed pattern. These results are consistent with others [l-3] suggesting that the spatial distribution of arms around the center platform has relatively little influence on performance on the radial arm maze. Many discussions of hippocampal function have emphasized the impairment of animals with damage to the hippocampal system in spatial [53-581 or cognitive mapping [59-W tasks. The results reported here are not inconsistent with these views, but require an extension of them to include consideration of the type of memory required by the task. Considerable debate has taken place concerning the role of the hippocampus in memory, Particularly
MF&fORYA&D HIPPOCAMPAL FUSCTIOS
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for animals [69-74. The experiment reported here used a within-subject, within-test design to demonstrate a dissociation of performance on bvorking memory and reference memory tasks. Because all aspects of these tasks were the same except for the memory requirement, factors in common to both of them (such as the type of motivation, the sensory properties of the cues, etc.) cannot be used to explain the observed dissociation. These results provide strong support for the hypothesis presented here, that the critical variable is the type of memory required by the two tasks. rlckno,cleclgenrents-This research was supported in part by Research Grant I-ROI-MH-23213 from the National Institute of Mental Health, and by a Biomedical Sciences Research Grant from The Johns Hopkins University. The authors thank A. BLACK, J. BECKER, G. HANDEL~IANY, L. JARRARD, L. NADEL, S. MITCHELL, J. O’KEEFE, J. RANCH and especially M. MISHKIX for comments on the manuscript, and P. HOLDES, E. KELS~ARTIS and J. KRACH for typing.
REFERENCES of places passed: spatial memory in rats. J. e.rp. I. OLTO~, D. S. and SA>IUELSO>. R. J. Remembrance Psfchol.: Anirnol Behov. Proc. 2, 97-l 16. 1976. in 2. OLTON, D. S., COLLISON, C. and WERZ, M. A. Spatial memory and radial arm maze performance rats. Learn. ,\lotiv. 8, 289-314, 1977. of spatial memory. In Cogrririve Aspects of Animal Eehnvior. S. H. HULSE, 3. OLTOS, D. S. Characteristics W. K. HONIG and H. FOWLER (Editors). pp. 341-373. Lawrence Eribaum, Hillsdale, 1978. 4. OLTOS, D. S., HANOELMANN, G. E. and WALKER, J. A. Spatial memory and food searching strategies. In Foraging Behnvior. A. KA~IIL and T. SERGENT (Editors), Garland STPM Press, New York. In press. OLTOS, D. S. Mazes, maps, and memory. rlfn. Psychol. In press. Ontario, :: ROBERTS, W. A. Some studies of spatial memory in the rat. Can. Psychol. Assn., Ottawa, Canada. 9 June 1978. 7. MAKI, W. S., BROKOFSKY, S. and BERG, S. Spatial memory in rats: Resistance to retroactive interference. Aninr. Lent-n. Behav. In press. 8. ZOLADEK, L. and ROBERTS, W. A. The sensory basis of spatial memory in the rat. Aninr. Learn. Behav. 6, 77-8 I, 1978. 9. BLACK, A. H., AUGERISOS, G. and SUZUKI, S. Stimulus control of behavior on the 8 arm maze. Can. Psychol. Assn., Ottawa, Ontario, Canada, 9 June 1978. IO. SUZ~~KI. S., AU~,ERISOS, G. and BLACK, A. H. Stimulus control ofspatial behavior on theeight arm maze in rats. Learn. ,Lloliv. In press. I I. OLTOS. D. S. and COLLISON. C. Intramaze cues and “odor trails” fail to direct choice behavior on an elevated maze. Atrim. Learn. Behav. In press. I?. W,\LRER, J. A. and OLTOY, D. S. The role of response and reard in spatial memory. Lent-n. Mofiv. In press. 13. OLTON, D. S., WALKER, J. A. and GAGE, F. H. Hippocampal connections and spatial discrimination. Brnin Res. 139, 295-308, 1978. function and behavior: Spatial discrimination and 14. OLTOS, D. S. and WERTZ, M. A. Hippocampal response inhibition. Physiol. Behav. 20, 597-605, 1978. 15. OLTON, D. S. The function of septo-hippocampal connections in spatially organized behaviour. In Fumions of the Sepro-HippoconlpnlSysfetn, Cibn, Fdn Synrp. 58, pp. 327-342. Elsevier, New York, 1978. 16. WALKER, J. A. and OLTON, D. S. Spatial memory deficit following fimbria-fornix lesions: Independent of time for stimulus processing. Physiol. Behov. In press. 17. HA~DELLIANN, G. E., COYLE, J. T. and OLTON, D. S. Lesions of CA3 pyramidal cells with kainic acid impairs spatial memory in rats. Sociery for Neuroscience, 8th Anneal Meefing 4, 221, 1978 (Abstract). IS. BECKER, J. T., WALKER, J. A., OLTON, D. S. and O’CONNELL. B. C. Neuroanatomical bases of shortterm spatial memory in the rat. Sociery for IVerrroscience, 8tl1 Annrm[ Meeting 4. 73, 1978 (Abstract). 19. JARRARD, L. E. Hippocampal lesions and spatial discrimination. J. camp. Phgsiol. Psychol. In press. 20. JARRARD. L. E. Selective hippocampal lesions and spatial discrimination in the rat. Society for iVewoscience, 8th Anrwal
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24. JARRARD, L. E. Role of interference in retention by rats with hippocampal lesions. J. camp. Physiol. 89,4OQ--tO8, 1975. 25. HONIG, W. K. Studies of working memory in the pigeon. In Cognitive rlspecrs of Animal Behaviour. S. H. HCLSE. W. K. HOSIG and H. FOWLER (Editors), pp. 21 l-248. Lawrence Eribaum Associates, Hillsdale, 1978. 26. NORCIAN, D. A. What have animal experiments taught us about human memory? In The Physiological Basis of .Wemory. J. A. DEUTSCH (Editor). Academic Press, New York, 1973. 27. LYSCH, G., MATTHEWS, D. A., MOSKO, S., PARKS, T. and COTSIAN, C. W. Induced acetylcholinesteraserich layer in dentate rat dentate gyrus following entorhinal lesions. Bruin Res. 42, 31 l-318, 1972. 28. LYSCH, G. and COTUAN, C. W. The hippocampus as a model for studying anatomical plasticity in the adult brain. In The Hippocumpra, R. L. ISAACSON and K. H. PRIBR.A.M(Editors), Vol. 1. pp. 123-154. Plenum Press, New York, 1973. 29. PELLEGRISO, L. J. and CUSHMAN, A. H. A Stereotuxic AIIUS of rhe Rut Bruin. Appleton-Century-Crofts, New York, 1967. 30. SIEGEL, S. ~Vonporumerric Srufisrics for rhe Behavioral Sciences. %lcGraw-Hill, New York, 1956. 31. SCH~~ALTZ. L. W. and ISSACSON, R. L. The effects of preliminary training conditions upon DRL performance in the hippocampectomized rat. Physiol. Behav. 1, 175-182, 1966. 32. JOHNSOS, C. T., OLTOS, D. S., GAGE, F. H. III and JENKO, P. G. Damage to hippocampus and hippocampai connections: Effects on DRL and spontaneous alternation. J. contp. Physiol. Pswhol. 91, 508522, 1977. 33. DOUGLAS, R. J. The hippocampus and behavior. Psychol. Bul/. 416-442, 1967. 34. GREENE, E. and STAUFF, C. Behavioral role of hippocampal connections. Ex~. Nellrol. 45,141-160, 1953. 35. JARRARD, L. E. Anatomical and behavioral analysis of hippocampal cell fields in rats. J. camp. Physiol. Psychol. 90, 1035-1050, 1976. 36. KI.MBLE, D. P. The effects of bilateral hippocampal lesions in rats. J. camp. Physiol. Psychol. 56,273-283, 1963. 37. SINNAMON, H. M., FRENIERE, S. and KOOTZ, J. Rat hippocampus and memory for places of changing significance. J. camp. Physiol. PsychoI. 92, 112-155, 1978. 38. OLTON, D. S. Behavioral and neuroanatomical differentiation of response-shift and response-suppression mechanisms in the rat. J. camp. Physiol. Psychol. 78, 450456, 1977. 39. HIRSCH, R. Lack of variability or preservation: Describing the effect of hippocampal ablation. Physiol. Behuv. 5, 1249-l 254. 1970. 40. ALTMAN, J., BRUNNER, R. L. and BAYER, S. A. The hippocampus and behavioral maturation. Behuv. Biol. 8, 557-596. 1973. 41. ISAACSON, R. L. The Limbic System. Plenum, New York, 1974. 42. KI.~BLE, D. P. Hippocampus and internal inhibition. Psychol. 81111.00, 285-295, 1968. retention with special 43. WARRISGTON, E. K. and WEISKRANTZ, L. A new method of testing long-term reference to amnesic patients. Nucflre, Lond. 217, 972-974, 1968. 44. WARRIPL;GTOS, E. K. and WEISKRANTZ, L. Organizational aspects of memory in amnesic patients. Nerrropsychologiu 9, 67-73. 197 I 45. WARRINGTOX, E. K. and WEISKRANTZ, L. The effect of prior learning on subsequent retention in amnesic patients. Newopsychologiu 12, 419-428, 1974. 46 WEISKRANTZ, L. A comparison of hippocampal pathology in man and other animals. In Flirnctjons of the Sepro-Hippocumpul System, Cibu Fdn Symp. 58, 373-387. Elsevier, New York, 1978. 47. WEISKRANTZ. L. and WARRINGTON, E. K. Verbal learning and retention by amnesic patients using partial information. Psychon. Sri. 20, 210-21 I, 1970. 48. WEISKRANTZ, L. and WARRINGTON, E. K. A study of forgetting in amnesic patients. Neuropsychologiu 8, 281-288, 1970. in man and animals. 49. WEISKRAXTZ, L. and WARRINGTON, E. K. The problem of the amnesic syndrome In The Hippocumplls. R. L. ISAACSON and K. H. PRIBRA.M (Editors), Vol. 2, pp. 41 l-428. Plenum Press, New York. of paired-associate learning in amnestic patients. 50. WINOCUR, B. and WEISKRANTZ, L. An investigation Nertropsychologiu 14, 97-l IO, 1976. 51. MILNER, B. Preface: Material specific and generalized learning loss. Neuropsychologia 6, 175-179, 1968 52. MILNER, B., CORKIN, S. and TEUBER, H.-L. Further analysis of hippocampal amnesic syndrome: A 14 year follow-up study of H.M. Newopsychologiu 6, 215-234, 1968. lobe ablation. Neuro53. MAHUT, H. Spatial and object reversal learning in monkeys with partial temporal wychologiu 9, 409-429, I97 I. 54. MAHUT. H. A selective spatial deficit in monkeys after transection of the fornix. Netrropsychofogiu 10, 55-74. 1972. specific impairment in spatial learning after fornix lesions 55. MAHUT, H. and ZOLA, S. M. A nonmodality n monkeys. Neuropsychologiu It, 225-269, 1973.
%tE.LIORY AND HIPPOCAMPAL FC’NCTION
681
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Rdsum6
On
a
teste des rats
sur la retention .4 branches
radlales
tait
2 series
mais
de nourriture
La reponse
avec
post-op6ratoire apprise
de branches.
dans
cette
serie
Btait
de ne pas y p&nGtrer.
chacune
wait
au debut
la tkhe
de "memoire dans
approche
de chacune
courir
toute
proches
normales
de travail" 16gSrement lesions
plus
perturbees
par
fimbria-fornix
d'am6lioration
dans
la r6ponse
correcte
Btait
la nourriture.
correcte
etait
les petite*
suggerent
une
les ap-
les grandes
lesions.
Chez
de
“memoire
lesions
les rats
on ne constatait
de travail".
et dans
de reference"
sur la tkhe
par
implication
de travail"
de par-
A toutes
A la fin du test post-opera-
complSte*,
la "memoire
de*
de ne pas y penetrer
de "m&moire
perturb&es
les plus dans
la "m&moire
a chacune
A la premiere
les performances
gravement
dent
representait
correcte
de nourriture.
que
de nourriture
du test.
sur la tache
tandis
3 chaque
de branches
au tours
obtenir
la reponse
etaient
comportementales campe
pour
approche s6rie
ja-
de r8fkrence".
La reponse
changeait
des branches,
les performances
etaient
signe
de travail". s6rie
n'y avait
toute
compor-
on ne mettait
de "memoire
second
du test un morceau
la branche
suivantes,
puisqu'il toire,
cette
pour Une
et du fornix
de labyrinthe
Le labyrinthe
sur laquelle
une epreuve
branche
branches
de la fimbria
discrimination
pr6-operatoirement. Une serie
representait
correcte
lesion
d'une
et
avec aucun
Ces dissociations
differente la "memoire
de l'hippode ref6rence".
682
D.AVID S. OLTON
Deutschsprachige Ratten
Zusaxmenfassung:
nit Schadigung
postoperative
and BARBARA C. PAPAS
der Fimbriae
Gedachtnis
krininationsnuster
getestet.
eines strahlenfdrmigen
des Fornix wurden
fiir ein praoperativ ZS
muf3te die raumliche
Irrgartens
behalten
setzte sich aus zwei Arten von GBngen hielt nienals Gedachtnis bestand
Futter,
werden.
zusanmen.
Das richtige
Verhalten
Eine zweite Anordnung
weils bei Testbeginn
fitter enthielt,
dachtnis
Das korrekte
betrachtet.
GBnge in diesem Bercich wechselte
Einer davon ent-
bei jeden Versuch
wUhrend
die korrekte
in jedem dieser
des Testversuchs.
bestand
in dem sich das fitter befand.
fen,weil.nun
war es korrekt,
das Futter nicht nehr
Ende der Untersuchung,
sionen
Verhalten Weise
ist.
unbeeintrachtigt
zu lau-
spricht
erwies
geblie-
bei ausgedehnten
hatte, bei leichteren
campus
in verschiedener
In allen
nicht dorthin
das "working"-Gedachtnis
stark gelitten
darin, in
nach Durchfiihrung der Operation,
Dieses unterschiedliche bezogen
Antwort
zur Verfiigung stand. Bei
sich, da0 das "reference"-Gedachtnis ben war, wghrend
die je-
w-urde als "working"-Ge-
Verhalten
Beim ersten Versuch
Versuchen
Bereich
von Gsngen,
den Gang zu laufen, nachfolgenden
Verteilung Der irrgarten
in diesen nicht mit Futter versehenen
nicht einzutreten.
Dis-
er wurde als Test fiir tin "referencetl-
angesehen.
darin,
auf das
erlerntes
Schaden
La-
geringer.
dafiir, clal3dcr Hippe-
in die Gedachtnisfunktionen
ein-