CAUDATE, CORTICAL, HIPPOCAMPAL AND DORSAL THALAMIC

Neuropychologia, 1965, Vol. 3, pp. 53 to 68. Pereamon Press Ltd. Printed in England

CAUDATE, CORTICAL, HIPPOCAMPAL AND DORSAL THALAMIC LESIONS IN RATS:

ALTERNATION AND HEBB-WILLIAMS MAZE PERFORMANCE

CHARLES G. GROSS, STEPHAN L. CHOROVER and SHOEL M. COHEN

Department of Psychology, Massachusetts Institute of Technology, Massachusetts, U.S.A.

(Received 28 September 1964)

Abstract-Rats with lesions of caudate nucleus, of anterior cortex, of posterior cortex, of dorsal hippocampus, of ventral hippocampus or of dorsomedial thalamic structures were trained on a two-bar alternation task and in a Hebb-Williams maze. The experiments had the following principal aims: (1) to further analyze the alternation deficit previously found to follow caudate lesions; (2) to determine whether those neural structures necessary for alternation performance in the monkey, viz., frontal granular cortex, hippocampus and caudate nucleus are also necessary for alternation in the rat and (3) to test the hypothesis that Lashley’s findings of increasingly deficient maze performance with increasing size of cortical lesion might be ascribed, at least partially, to increasing encroachment on an anterior cortical region critical for alternation and a posterior cortical region critical for visually guided behavior.

We found that alternation was impaired by caudate lesions, by hippocampal lesions, by anterior cortex lesions and by thalamic lesions that included the dorsomedial nucleus. By contrast, Hebb-Williams maze performance was only impaired by posterior cortex lesions, by lesions that included the lateral geniculate bodies and by large medial thalamic lesions.

The alternation deficit could not be accounted for in terms of changes in activity level, motivation, memory or response perseveration. As in the monkey, integrity of the caudate nucleus, the cortical projection of the dorsomedialnucleus and the hippocampus appear necessary for normal alternation performance. Finally, the present results support Hunter’s interpretation that Lashley’s “mass action” results may be attributed to progressive enroachment on specific “critical” regions.

1. INTRODUCTION

IN AN earlier study, caudate nucleus lesions in rats were found to impair performance of a task requiring alternation between two bars, but not performance in a Hebb-Williams maze. A control group with posterior cortex lesions showed an opposite effect, viz.,‘impaired maze performance but normal alternation (CHOROVER and GROSS [4]). In that alternation task, the bars were always available and Ss received food after each alternated bar press. The inter-response time thus consisted of response latency plus eating time. In the alternation task in the present study the bars were also always available but presses on the left and right bars had different effects: Ss received food only after a single right press preceded by a single left press. Since with perfect performance, food was presented only after every other response, the minimum inter-response time was less than in the previous study. Effects of caudate nucleus lesions were again contrasted with effects of posterior cortex lesions. In addition, we examined the effects of lesions of anterior cortex, of the hippocampus and of the dorsomedial nucleus of the thalamus on this alternation task. Ss with lesions of anterior cortex or of the hippocampus were included because, in the monkey, integrity of frontal

53

54 CHARLES G. GROSS, STEPHAN L. CHOROVER and SHOEL M. COHEN

granular cortex,* the hippocampus, as well as of the caudate nucleus, is necessary for normal alternation performance (JACOBSEN and NISSEN [15]; PRIBRAM et al. [36]; PRIBRAM et al. [37]; ROSVOLD and SWARCBART [42]; ROSVOLD and DELGADO [41]; DEAN and DAVIS [6]).

Inclusion of Ss with dorsomedial nucleus lesions was motivated by the finding that large subtotal lesions of this nucleus, in the monkey, do not impair alternation performance (WALKER [51]; CHOW [5]; PETERS et al. [34]). This is somewhat puzzling since the dorsomedial nucleus provides one of the principal subcortical inputs to frontal granular cortex. [However, total destruction of the dorsomedial nucleus in monkeys has recently been reported to impair a related task, delayed response (SCHULMAN [43]).] Thus Experiment I affords a comparison of the effects of homologous lesions in the rat and monkey on a similar task.

In Experiment II, the various lesion groups were tested in a Hebb-Williams maze. One purpose of this experiment was to provide a control task for the alternation study, that is, to determine the specificity of the effects of any lesions that impaired performance of the alternation task.

In addition, Experiment II had a broader aim. LASHLEY [25, 271 had interpreted the increasing impairment of maze performance with increasing size of lesion as an instance of cortical mass action. This interpretation has been challenged by HUNTER and others (HUNTER [l I] ; MORGAN and STELLAR [31] ; ZANGWILL [54]), who preferred an explanation in terms of increasing encroachment on critical regions. Experiment II provides a test of such an interpretation of LASHLEY’S results. The mazes used by LASHLEY in his “mass action” studies required both spatial alternation and visual discrimination. Lesions of anterior cortex, but not posterior cortex have been shown to impair alternation in T-mazes (LOUCKS [29]; MORGAN and WOOD [32]; HUNTER and HALL [12]; PICKETT [35]). In a Hebb-Williams maze [which has been considered to be a primarily visual task (HYMOVITCH [13] ; FORGAYS and FORGAYS [7] ; LANSDELL [23] ; SMITH [44])], LANSDELL [23] found lesions of posterior cortex but not of anterior cortex to impair performance. Thus LASHLEY’S findings might be at least partially understood in terms of increasing invasion of an anterior cortical region critical for spatial alternation and a posterior cortical region critical for visually guided behavior. One difficulty with this hypothesis is that LANSDELL’S rats were raised in a free-environment: SMITH’S [44] results indicate that the effects of cortical lesions on Hebb-Williams maze performance are more locus-specific in free-environment rats than in cage-reared rats. Experiment II eliminates this difficulty by providing a direct comparison for cage-reared rats between effects of anterior and posterior lesions on performance in a Hebb-Williams maze.

2.1. Subjects 2. METHOD: EXPERIMENT 1

One hundred and thirteen experimentally naive male Long-Evans hooded rats were used. They were about 120 days old at the start of the experiment and were housed individually with free access to water at all times. For about ten days prior to the beginning of the experiment, and before and after surgery, food (Purina Laboratory Chow) was continuously available. At other times the Ss were maintained at 80 per cent of the weight attained at the end of the previous ad lib. feeding period.

* Cortex on the dorsal surface of the frontal pole in the rat has been homologized with frontal granular cortex in the monkey (GURDJIAN [IO], LE GROS CLARK [28], LASHLEY [26], ROSE and W~~LSEY [40]).

LESIONS AND PERFORMANCE IN RATS 55

2.2. Apparatus and test procedure A Grason-Stadler two-lever box (Model E 3125 B) was used. A 45 mg food pellet

(reinforcement) could be delivered to a food-well located between the two levers. Reinforce- ment was accompanied by illumination of the food-well for $ sec. A single press on the left bar, followed by a single press on the right bar resulted in presentation of a pellet. After the inital bar-press, each successive press on either bar not preceded by a press on the other bar was followed by a 5 set time out. If the initial bar press was on the right bar, i: was also

followed by a 5 set time out. During the time out, the houselights were extinguished and presses to either bar had no consequence. Each daily session lasted until 300 responses

(excluding responses during time out) had been made. Responses other than those in the

time out are termed trials. Training was continued until the criterion of 80 per cent of optimal performance (i.e., 120 rewards) on 4 out of 5 consecutive days was achieved or until 13,000 trials had been run, whichever was less.

2.3. Experimental design After being trained to bar press, Ss were reinforced for every response to either bar for

50 reinforcements per day for 2 days. On the following 2 days they were run for 50 reinforcements per day scheduled so that runs of more than five successive responses to either bar were not reinforced.

After this preliminary training, Ss were allowed free access to food for about 10 days

and then either underwent surgery or were kept as unoperated controls. Twelve Ss recerved bilateral lesions of the caudate nucleus, thirteen received bilateral lesions of posterior

cortex, six Ss received bilateral lesions of dorsal hippocampus, five Ss received bilateral lesions of ventral hippocampus, and 77 Ss served as unoperated controls. These I1 3 rats were the Ss for the acquisition phase of the experiment. (There were no Ss with anterio; cortical or dorsomedial lesions in this phase of the experiment.) Two to three weeks later, Ss were again reduced to 80 per cent of their previous ad lib. weight and run on the alternation task described above.

Following attainment of criterion in the acquisition phase, the unoperated Ss were

given free access to food. Fifty-three of them became Ss for the retention phase of the experiment. Twelve received bilateral caudate nucleus lesions, six received bilateral anterior cortex lesions, ten received bilateral posterior cortex lesions, six received bilateral dorsal hippocampus lesions, six received bilateral ventral hippocampus lesions, six received bilateral lesions aimed at the dorsomedial nucleus of the thalamus, and seven served as unoperated controls. Three to four weeks after surgery these Ss were run on the task until they reached criterion or for 13,000 trials, whichever was less.

2.4. Surgical and histological procedures Subcortical lesions were made with a Grass Model LM-2 lesion maker through a

formvar-coated wire (0.01 in. dia.) with insulation removed from the tip. The caudate and thalamic groups received a single lesion on each side whereas the hippocampal groups received multiple bilateral lesions. Cortical lesions were made by aspiration.

When the experiments were completed, operated Ss were anesthetized with pento- barbital, perfused with 10 per cent formalin and their brains removed, fixed, dehydrated, embedded, sectioned at 10 p and stained with cresyl violet or thionine. Cortical lesions were reconstructed onto Lashley diagrams on the basis of every tenth section. Reconstructions


of representative cortical lesions are shown in Fig. 2 and 3. Sections through these lesions were also checked for subcortical damage. Every tenth section through the subcortical lesions were examined and traced. Tracings of sections showing the maximal extent of representative subcortical lesions are given in Figs. 1, 4, 5 and 6.

FIG. 1. Cross sections of representative caudate nucleus lesions. The numerals in the upper right corner of each cross section refer to the anterior-posterior level of the cross section in the system of KSNIG and KLIPPEL [21].

m

FIG. 2. Reconstructions of representative posterior cortex lesions with corresponding pattern of degeneration in lateral geniculate nuclei. See also legend to Fig. 1.

LESIONS AND PERFORMANCE IN RATS

129 13, (33

FIG. 3. Reconstructions of anterior cortex lesions

I

, p

FIG. 4. Cross sections of representative dorsal hippocampus lesions. See also legend to Fig. 1.

FIG. 5. Cross sections of representative ventral hippocampus lesions. See also legend to Fig. 1.


FIG. 6. Cross sections of dorsal thalamus lesions. See also legend to Fig. 1.

2.5. Data analysis Comparisons between groups were made with two-tailed Mann-Whitney “U” tests.

Within a group the relation between size and site of the lesion and post-operative performance was examined by median tests and by testing the significance of Spearman’s rank correlation coefficient.

The measure “trials to criterion” does not include the 1500 criterion trials. The savings measure equalled :

post-operative trials to criterion+preoperative trials to criterion

post-operative trials to criterion-preoperative trials to criterion’

For statistical comparisons involving either measure, Ss that failed to attain criterion in 13,000 trials were ranked on the basis of the per cent correct in the final 1500 trials.

3.1. Acquisition 3. RESULTS: EXPERIMENT I

The posterior cortex group, acquired the modified alternation task as rapidly as did the unoperated animals. There was no relation between the site or size of lesions and rate of acquisition within this group.

Ss with caudate lesions were severely impaired on this task relative to both unoperated controls (p<O.O0006) and Ss with posterior cortex lesions (p<O.O02). Although all Ss in the caudate group had bilateral damage to the caudate nucleus, there was considerable variation in the size and location of the lesions. Some of the lesions encroached upon adjacent structures (e.g. nucleus accumbens, anterior commissure, and the genu of the corpus callosum), but there was no relationship between either the size of the lesion or the adjacent structures involved and the degree of deficit.

The dorsal hippocampus group was impaired relative to both unoperated Ss (p < 0.004) and to posterior cortex operates (p < 0.05). One S in the dorsal hippocampus group (No. J 16) acquired the task in less than the mean number of trials of the control Ss and only three Ss were severely impaired (Nos. J19, 522, 532). The lesions of these three Ss were larger and extended more posteriorly than the lesions of the other Ss.


The ventral hippocampus group was also impaired relative to both the unoperated Ss (p < 0.004) and posterior cortex Ss (p < 0.05). One S in this group (No. 5211) was much more severely impaired than the other ventral hippocampus animals. It had much more massive damage to hippocampus and adjacent structures than the other ventral hippocampal animals.

The three impaired groups, (caudate, dorsal hippocampus, and ventral hippocampus) did not differ significantly from each other in the number of trials required to reach criterion. The results of the acquisition phase of the experiment are summarized in Fig. 7.

ACQUISITION OF ALTERNATION

3.2. Retention

N: 77 12 13 6 6

FIG. 7. Mean trials to criterion on acquisition of the alternation task. Ss failing to reach criterion in 13,000 trials were assigned the score of 13,000, Abbreviations: Norm., normal; Cau., caudate; P. C., posterior cortex; D. H., dorsal hippocampus; V. H., ventral hippocampus.

As in the acquisition phase, the unoperated and posterior cortex groups were similar; both showed excellent post-operative retention. Again, there was no relation between performance and lesion extent in the posterior cortex group.

The caudate lesion group was severely impaired relative to both the unoperated and posterior cortex groups in terms of post-operative trials to criterion (p < 0.002; p < 0.002) and savings (P-C 0.002; p< 0.002). There was no discernable relation between the site of damage within the caudate or adjoining structures and retention. But, there was a significant relation between the size of the caudate lesions and retention (p=O.53, ~~0.05).

The dorsal hippocampus group showed much poorer retention than either the unoperated or posterior cortex groups both in terms of trials (p c 0.002; p < 0.002) and savings (p < 0.002; p < 0.02) (the lesions of this group were intermediate in size and posterior extent as compared with the dorsal hippocampus group in the acquisition phase).

Although differences between the ventral hippocampus group and the unoperated and posterior cortex groups were significant beyond the 0.05 level in both trials and savings, it would be misleading simply to designate the ventral hippocampus group as impaired. Of the six Ss in this group, one was completely unimpaired (526) and another showed, at most, a very slight deficit (58).


The anterior cortical group retained the task more poorly than either the unoperated control group (p<O.O02 on both measures) or the posterior cortex group (p ~0.02 on both measures). One S (No. 117) in the anterior cortex group showed normal retention of the task. This was the only S in the group whose lesion did not include the anterior dorsal surface of the frontal poles.

The group with lesions aimed at the dorsomedial nucleus of the thalamus was impaired relative to the unoperated group (p~O.04, both measures) and the posterior cortex group (p< 0.05, both measures). One S (No. 111) showed perfect retention of the task; the remain- ing five failed to reattain criterion in the allotted 13,000 trials. All Ss which failed had massive damage to the dorsomedial nucleus and adjacent areas except for No. 199. The lesion of this S was confined to the dorsomedial nucleus. The lesion of the unimpaired S (No. 111) was similar in size to that of No. 199 but spared the dorsomedial nucleus.

The results of the retention phase are summarized in Fig. 8.

RETENTION OF ALTERNATION

12Or

GR6UP: NORM. CAU. A.C I? c. D.T. D.H. V.H.

N 7 12 6 IO 6 6 6

FIG. 8. Mean trials to criterion on post-operative retention of the alternation task. Ss failing to reattain criterion in 13,000 trials were assigned the score of 13,000. Abbreviations: Norm., normal; Cau., caudate; A. C., anterior cortex; P. C., posterior cortex; D. T., dorsal thalamus; D. H., dorsal hippocampus; V. H., ventral hippocampus.

3.3. Analysis of response patterns Since there were no significant differences in post-operative trials to criterion or savings

among the impaired groups (caudate, hippocampus, anterior cortex, dorsomedial), an attempt was made to discover differences in the pattern of responses or errors among them or between them and the unimpaired groups.

The various groups in both acquisition and retention phases did not seem to differ in their response perseveration tendencies : they made similar numbers of bar presses per time out period and had similar ratios of left to right presses during time out. As another test for response perseverative tendencies, selected sessions from Ss in the cortex and caudate acquisition and retention groups were analyzed for the distribution of consecutive errors made2,3... n times in a row. When these sessions were equated for per cent correct trials, there were no differences in the distribution of consecutive errors between the two groups,


During the latter part of the acquisition phase and throughout the retention phase of the experiment, impaired groups responded proportionately more on the right bar than did unimpaired groups (p < 0.02). However, this tendency to prefer the right bar was correlated with the accuracy of performance per se and did not discriminate among groups with different lesions.

Mean inter-response intervals of the operated groups (retention phase only) tended to be greater than those of the normal group; these differences attained significance only for the caudate (p < 0.02) and ventral hippocampus (p < 0.04) groups. There were no significant differences, however, in the mean inter-response interval among the operated groups or any correlation with performance in any group.

4.1. Subjects 4. METHOD: EXPERIMENT II

The 55 Ss had been Ss in Experiment I or in the alternation experiment reported previously (CHOROVER and GROSS [4]) and in tests of passive and active avoidance. Thirteen had received caudate nucleus lesions, eight had received bilateral posterior cortex lesions, eight had received bilateral dorsal hippocampus lesions, six had received bilateral ventral hippocampus lesions, six had received bilateral anterior cortex lesions, six Ss had received bilateral lesions aimed at the dorsomedial nucleus of the thalamus, and nine Ss continued to serve as unoperated controls.

4.2. Apparatus and procedure The apparatus and procedure were similar to those described by RABINOVICH and

ROSVOLD [38], with the following exceptions: (a) the height of the maze walls and barriers was 10 in. and no screen top was used, and (b) Ss were run after 23 hr of food deprivation on one problem per day.

Statistical comparisons between the groups utilized two-tailed Mann-Whitney tests.

5. RESULTS: EXPERIMENT II

Although they had been the least impaired operates in Experiment I, the posterior cortex group made many more errors in the maze than the unoperated group (p < 0.002), the caudate group (p<O.O02), the dorsal hippocampus group (p ~0.002) or the anterior cortex group @<0.002). The unoperated, caudate, dorsal hippocampus and anterior cortex groups did not differ significantly among themselves (Fig. 9). Furthermore, there were no significant or suggestive relations between size of lesion and error score within each or among these five groups.

The within-group performance of the ventral hippocampus group and the dorsomedial group was not uniform. These performance variations appeared to be related to lesion variations. In the ventral hippocampus group, number of errors was correlated with both size of lesion (p=O.86, ~~0.05) and with degree of encroachment on the lateral geniculate body (p=O.96, ~~0.01).

In the dorsomedial group, two Ss sustained virtually total damage of the medial, intralaminar and midline nuclear groups (No. 123 and 125). These Ss were severely impaired in the maze. The other Ss in this group, with smaller lesions, fell within the normal range of performance.


FIG. 9. Mean errors on the twelve Hebb-Williams maze problems. Abbreviations: Norm., normal; Cau., caudate; A. C., anterior cortex; P. C., posterior cortex; aD. T., large dorsal thalamus (Nos. 123 and 125); bD. T., other dorsal thalamus Ss; D. H., dorsal hippocampus; .V. H., ventral hippocampus Ss with lesions that encroached bilaterally on the lateral geniculate nucleus; dV. H., Ss with lesions that totally or unilaterally spared the lateral geniculate nucleus.

6. DISCUSSION

6.1. Experiment I: alternation

61.1. Possible bases of the alternation deficit. Experiment I indicated that anterior cortex, caudate nucleus, hippocampus and dorsal thalamic structures are essential for performance of the alternation task. As is often the case, it is easier to state what the basis of the deficit produced by these lesions is not than to determine what it is.

The impairment on our modified alternation task could not have been due to generalized deterioration in behavior since the groups deficient on the alternation task were not impaired in Hebb-Williams maze performance (Ex. II).

An increase in activity level might be expected to impair performance on our task. We did not measure locomotor activity but observation and response latency measurements in both the alternation and maze situations did not reveal any increased activity by Ss impaired on alternation. Furthermore, previous investigators have found that, in the rat, caudate lesions increase activity only transiently (WHITTIER and ORR [53]) and lesions comparable to our anterior cortical lesions do not change activity (ZUBECK and LORENZO [55]). Studies of hippocampus lesions (usually larger than ours) have yielded conflicting effects on locomotor activity (KIM [20] ; KAADA et al. [16] ; TEITELBAUM and MILNER [46] ; DOUGLAS and ISAACSON [6a]).

A change in the effect of food deprivation (i.e., a motivational change) is also an unlikely basis of the deficit for two reasons. The first is the failure of caudate lesions to affect bar pressing reinforced on a fixed interval schedule under various levels of deprivation (KESLER [IS]). [Fixed interval schedules are sensitive to food deprivation level (WEISS and MOORE [52]).] The second is that Ss which failed the alternation task continued to show normal motivation (as indicated by observation and response latency measures) in both the alternation and maze situations.


The absence of any intra-trial delay in our alternation situation makes it rather difficult to characterize the deficit as one of recent memory. Furthermore, two findings argue

against interpretation in terms of disinhibition or response perseveration. The first is the absence of any difference among the groups in number of bar presses per time out period. The second is the absence of any difference between impaired and unimpaired Ss in the number of successive presses on one bar at comparable levels of performance. The alterna-

tion deficit may have reflected an impairment in learning or performing chained or sequential responses (LASHLEY [27]). However, since the groups impaired on alternation were not impaired on the Hebb-Williams maze, this interpretation must assume that such an impairment would not affect maze performance.

6.1.2. EfSects of caudate lesions. Although normal rats learned our previous alternation task (left press, reinforcement, right press, reinforcement, etc.) more quickly than the present one (left press, right press, reinforcement, etc.), the caudate operates showed comparable deficits on both tasks. Thus, by decreasing the inter-response time (response latency plus eating time) and by making each bar press have a different consequence, we did not seem to lessen the deleterious effect of the caudate lesions.

Our findings indicate that in the rat, as in the monkey, the degree of retention impairment on alternation is related to the size of the caudate lesion (ROSVOLD and SWARCBART

[421).

6.1.3. Effects of anterior cortical lesions. Many years ago LOUCKS [29] showed that anterior cortical lesions in rats impair performance of a 15 set delayed alternation task in a T maze. MORGAN and WOOD [32] replicated this result and also found that posterior cortex lesions did not impair performance of this task. Anterior cortex lesions have also been reported to impair single alternation (PICKETT [35]) and double alternation (HUNTER and HALL [12]) in a multiple T maze but in the former experiment all Ss were blind and in the latter no operated controls were included. The results of Experiment I clearly indicate that an inter-response delay is not required to produce an alternation impairment after anterior cortex lesions in the rat. That the only S in the anterior cortex group which was unimpaired on retention had the least destruction of the cortical projection of the dorsomedial nucleus of the thalamus strongly suggests that homologous neocortical tissue is required for normal retention of an alternation habit in rat and monkey.

6.1.4. EfSects qf hippocampal lesions. We know of no previous account of the effect of hippocampal lesions on an alternation habit in the rat, although such lesions have repeatedly been reported to reduce spontaneous alternation (GOLD [9]; ROBERTS et al. [39]; LASH [24]; DOUGLAS and ISAACSON [6a]). It would be interesting to know the effects of caudate, anterior cortex and dorsomedial thalamic lesions on spontaneous alternation. The variation in acquisition and retention performance within both the dorsal hippocampus and ventral hippocampus groups tended to be related to size of lesion. Differences in the site of the lesion within the hippocampus also have contributed to the within-group variance.

6.1.5. Effects of dorsomedial nucleus lesions. A!1 the Ss in this group that had lesions which included most of the dorsomedial nucleus failed to relearn the alternation task in the allotted 13,000 trials. The two with the largest lesions (involving most of the dorsal thalamus) were also impaired on the maze task, indicating a fairly non-specific effect of these lesions.

64 CHARLESG. GROWS, STEPHAN L. CHOROVER and SHOEL M.COHEN

However, the maximal alternation deficit of the single Ss whose lesions were confined to the dorsomedial nucleus suggests that this structure may play a more important role in alternation performance in the rat than in the monkey. [In the monkey subtotal lesions of the dorsomedial nucleus do not impair delayed alternation (WALKER [51] ; CHOW [5] ; PETERS et al. [34]) although larger dorsomedial thalamic lesions do appear to impair delayed response (SCHULMAN [43]).]

6.1.6. Comparison of alternation dejicit in the rat and monkey. In the monkey, frontal granular cortex, caudate nucleus and hippocampus appear to form part of a neural system involved in delayed alternation performance (ROSVOLD and SWARCBART [42]). Our results demonstrate that in the rat, integrity of homologous structures is necessary for performance of an alternation habit. Our alternation task differed from the one usually employed with monkeys by not having an intra-trial interval in which an opaque screen is interposed between S and manipulanda. However, with the exception of a study by BATTIG et al. [l], monkeys with frontal lesions have been found to be impaired on similar tasks in the absence of a screen, a delay period, or both (STAMM [45]; JACOBSEN [14]; BLUM [2]; PRIBRAM et al. [36]; ORBACH [33]; CAMPBELL and HARLOW [3]; FRENCH and HARLOW [S]). Therefore we may conclude that the caudate nucleus, the cortical projection of the dorsomedial nucleus and the hippocampus have functions in common in rat and monkey.

6.2. Experiment II: Hebb- Williams maze

6.2.1. Eficts of subcortical lesions. The deficient performance in the Hebb-Williams maze of some of the Ss with subcortical lesions was somewhat unexpected, particularly before examination of the lesions of these Ss. Two of the Ss in the dorsomedial group had unintentionally sustained large lesions of the dorsal thalamus. These Ss were severely impaired both on the alternation task and in the maze. Similarly, a non-specific impairment has been produced by electrical stimulation in this area (MAHUT [30]). These results and the reports of impairment on various shock-motivated tasks after destruction within this area (KAADA et al. [ 171; THOMPSON [47] ; VANDERWOLF [49, 501; THOMPSON and MASSOPUST [48]) suggest that it has an important but possibly non-specific role in learning.

Within the ventral hippocampus group there was a positive correlation between errors in the maze and both the size of lesion and the degree of encroachment on the lateral geniculate body. However, it was not possible to differentiate the relative roles of lesion size, and of lateral geniculate involvement in the production of the impairment in this group.

Near the completion of this experiment, two studies reported severe impairment on performance in the Hebb-Williams maze after hippocampus lesions-in contrast to our failure to find such impairment after dorsal hippocampus lesions and our smaller ventral hippocampus lesions. In the first study, by KIMBLE [19], the smallest hippocampal lesion was much larger than those of our unimpaired hippocampus operates. Furthermore, six of KIMBLE’S ten hippocampal Ss had lateral geniculate damage. In the second study, by KVEIM et al. [22], the lesions again seemed to have been larger than our ineffective lesions and to have included more of the anterior and dorsal regions of the hippocampus. It is possible that hippocampus lesions must exceed a certain size to impair HebbWilliams maze performance or that there may be regional differences in the effects of lesions on this task. Another possible source of the discrepancy is suggested by the work of REYNOLDS [38a] and DOUGLAS and ISAACSON [6a] who have shown that lesions of similar size made by different methods may exert dissimilar effects. Whereas our lesions were made by means of high- frequency alternating current, those of KIMBLE and KVEIM et al. were made by aspiration.


6.2.2. Efects of’ cortical lesions. Our results extend LANSDELL’S findings (with free

environment rats), that posterior but not anterior cortical lesions severely impair Hebb- Williams maze performance, to the more general case of cage-reared rats. Thus, for the first time, there is strong evidence in support of an interpretation of LASHLEY’S findings of a positive relation between size of cortical lesion and maze impairment in terms of increasing encroachment on critical regions. That is, LASHLEY’S results may be attributed, at least in part, to increasing encroachment, with increasing size of lesion, on an anterior cortical region critical for alternation and a posterior cortical region critical for visually guided behavior.

7. SUMMARY OF CONCLUSIONS

Lesions of the caudate nucleus, of anterior cortex, of the hippocampus or of dorsal thalamic structures produced impairment of an alternation habit in the rat.

The deficit on acquisition and retention of alternation found after these lesions could not be ascribed to a generalized deterioration in behavior, to changes in activity level or motivation nor to a deficit in memory, inhibition or to response perseveration. Interpretation of the deficit as one in response chaining may be possible.

Lesions of the dorsal thalamus or of posterior cortex impaired performance in a Hebb- Williams maze, unlike lesions of anterior cortex, caudate nucleus or the dorsal hippocampus.

LASHLEY’S findings of a positive relationship between size of cortical lesion and impairment in the LASHLEY III maze may be ascribed, at least partially, to encroachment on an anterior region critical for alternation and a posterior region critical for visually guided

behavior.

Acknowledgements-This research was supported under Grants MH-07923, MH-05673, and HD-01079 from the National Institutes of Health. Additional aid was received from NASA (NsG-496), from the U.S. Air Force Office of Scientific Research, and from the Rockfeller and Hartford Foundations. The authors express their gratitude to ANNE MARIE DELUCA and ANN CARPER for technical assistance, and to MARILYN MOHNKERN for preparation of the histological materials. HELEN MAHUT and W. J. H. NAUTA were kind enough to advise on the interpretation of the histological material.

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Resume-Des rats avec lesions du noyau caudt, du cortex anterieur, du cortex posterieur, de l’hippocampe dorsal, de l’hippocampe ventral ou des structures thalamiques dorsomedianes, Ctaient entrain& SLIT une tpreuve “d’alternation” sur 2 barres et dans un labyrinthe de Hebb- Williams.

Les experiences avaient les buts pricipaux suivants: 1. Poursuivre l’analyse du deficit de “l’alternation” constate deja apres lesion caudte. 2. Determiner si les structures nerveuses necessaires aux performances “d’alternation”

chez le singe, a savoir, le cortex granulaire frontal, l’hippocampe et le noyau caude sont aussi necessaires pour “l’alternation” chez le rat.

3. Tester l’hypothtse que les constatations faites par LASHLEY sur l’augmentation du deficit aux performances du labyrinthe parallelement a l’extension de la lesion corticale puissent &treattribu~es,aumoinspartiellement,~l’empittementdeplusenplusgrandsurlartgioncorticale anttrieure, critique pour “l’alternation” et sur la region corticale posterieure, critique pour le comportement guide optiquement.

Nous avons trouve que “l’alternation” ttait troublee par les lesions caudees, par les lesions hippocampiques, par les lesions du cortex anterieur et par les lesions thalamiques qui comprennent le noyau dorsomedian. A l’inverse, les performances au labyrinthe n’ttaient troublees que par les lesions du cortex posterieur, par les lesions touchant les corps genouilles externes et par de grandes lesions thalamiques medianes.

On ne pouvait pas rendre compte du deficit de “l’alternation” en termes de modification du niveau d’activite, de motivation, de m&moire ou de reponses perseveratrices. Comme chez le singe, pint&grit& du noyau caude, des projections corticales du noyau dorsomtdian et de l’hippocampe se rtvele necessaire pour la performance normale “d’alternation”.

Enfin, ces rtsultats sont en faveur de l’interpretation de HUNTER pour qui les resultats de I’ “actionde masse”de LasmFvpeuvent Ctre attribues a un empittement de plusenplus marque sur les regions “critiques” sptcifiques.

Zusammenfassung-Ratten mit verschiedenen Himlasionen wurden anzwei Aufgaben geprtift, und zwar erstens, an einer Aufgabe, bei der die Tiere zwischen zwei Tastern im Versuchskafig hin- und herwechseln mussten (Alternations-Priifung), und, zweitens, an einem offenen Labyrinth (nach Hebb und Williams).

Die gezielten Zerstorungen betrafen je eine der folgenden Hirnregionen: (a) Caudatum; (b) vordere Rinde (d.h., “Frontalkortex”); (c) hintere Rinde (“Okzipito-

parietaler Kortex”); (d) ventraler Hippocampus; (e) dorsaler Hippocampus; (f) Thalamus (Nucleus dorsalis medialis). Diese Experimente hatten ein dreifaches Ziel;

68 CHARLES G. GROSS, STEPHAN L. CHOROVER and SHOEL M. -HEN

1. Weitere Analyse eines Caudatum Symptoms, das schon frtiher nachgewiesen wurde, n%rnlich Mange1 an Alternierungsfahigkeit;

2. Nachprtifung, ob diejenigen Hirnstrukturen, die beim Affen fur normales Altemieren nbtig sind (d.h., granularer Frontalkortex, Hippocampus, Caudatum), such bei der Ratte eine entsprechende Rolle spielen, und, letzlich;

3. Untersuchung der Hypothese, ob die klassischen Befunde von Lashley tiber die Rolle der Himrinde im Labyrinthverhalten der Ratte neu interpretiert werden konnten: Lashley hatte entdeckt, dass die Labyrinthleistung der Ratte umso schlechter ist, je mehr von der Hirnrinde abgetragen wird, ohne dass die spezifische Lokalisation der Abtragung irgendeine Bedeutung hat. Wir versuchten stattdessen nachzuweisen, ob Lashley’s Resultate wenigstens zum Teil so verstanden werden kbnnen, dass grijssere Abtragungen eine vordere Rindenregion zerstBren, die kritischen Bedeutung fur das Alternieren hat, und zugleich eine hintere Rinden- region mit kritischer Bedeutung fur opt&h gesteuertes Verhalten.

Wir fanden, dass das Alternieren behindert wurde, wenn immer die LHsionen je eine der folgenden Himstrukturen betrafen: Caudatum, Hippocampus, vordere Rinde, medio- dorsaler Thalamus. Im Gegensatz zu diesen Befunden stellte sich heraus, dass Labyrinth- verhalten nur dann gestort war, wenn die Abtragungen die hintere Hirnrinde betrafen, oder die lusseren Kniehocker im Thalamus, oder grossere Anteile des mittleren Thalamus.

Die Leistungsiistrungen in der Alternationsprobe konnten nicht so gedeutet werden, dass man sie auf die folgenden Faktoren hatte zurtickftihren kiinnen: Verlnderungen im Aktivitltsniveau, in der Motivation, in der Gedlchtnisleistung, oder schliesslich in der Art, wie die Tiere auf ihren Reizantworten beharren. Keine von diesen Moglichkeiten konnten die ganz spezifische Unflhigkeit fur das Alternieren erkllren. Genau wie beim Affen, setzt die Fahiglceit fur normales Alternieren bei der Ratte voraus, dass sowohl das Caudatum unversehrt ist, wie such der Hippocampus, die kortikale Rindenprojektion des mediodorsalen Thalamus.

Letzlich best&ken unsere Versuchsergebnisse die Auffassung von Hunter, der darauf bestand, dass Lashley’s Beweis fur eine “Massenaktion” der Hirnrinde nicht so verstanden werden kann, wie es Lashley ursprtinglich meinte. Statt dessen verschlechtert sich das Labyrinth- verhalten der Ratte im proportionalen Verhaltnis zu der Rindenzerstiirung, weil grtisere Zerstbrungen fortschreitend auf verschiedene kritische Areale zugleich einwirken.

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CAUDATE, CORTICAL, HIPPOCAMPAL AND DORSAL THALAMIC

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