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A comparison of effects of orbitofrontal and hippocampal lesions upon discrimination learning and reversal in the cat
EXPERIMENTAL
i%EUROLOGY
9,
A Comparison Hippocampal Learning
452-462
(1964)
of
Effects
Lesions and
of Biology,
Orbitofrontal
and
Discrimination in the
Cat
TEITELBAUM’
California Received
Upon
Reversal
HERMAN Division
of
Institute January
of Technology,
Pasadena
17, 1961
In contrast to normals and brain-damaged controls, cats with bilateral hippocampal or orbitofrontal lesions are severely impaired in their ability to reverse tactile discrimination problems. These lesions do not interfere with discrimination learning per se, and do not affect the cat’s ability to learn new discrimination problems. Both effects are quantitatively and qualitatively similar. It takes either preparation more than twice as many trials than normal to master a reversal. The effect of removal of both structures in the same animal is not additive. Introduction
Although
the hippocampus and orbitofrontal cortex differ in cytoand in anatomical relations to other neural structures, the behavioral changes which take place after these structures are ablated are remarkably similar. For example, Morgan and Wood (10) and Loucks (7) have shown that rats lacking the frontal pole do not alternate as well as normals. Hippocampal lesions have a similar effect (12). According to Lichtenstein (6), passive avoidance performance is impaired by frontal lesions in dogs. Hippocampal lesions in rats result in an inability to perform passive avoidance tests as well (2, 5, 17). Deficits in delayed response and delayed alternation have been found in monkeys with either lesion (4, 9, 11, 15). Finally, increased response perseveration manifested in tests of extinction and habit reversal, are also seen after each lesion (3, 8, 16, 18, and Webster & Vonieda, unpublished). architecture
1 This investigation was carried out during the tenure of a USPH postdoctoral fellowship, the work being supported by a USPH grant (MH0.3372) to Professor R. W. Sperry. The author’s present address is: Pharmacology Department, Albert Einstein College of Medicine, New York, N. Y. 452
DISCRIMINATION
LEARNING
453
The purpose of the present experiment is to make a direct comparison of the severity and qualitative nature of the reversal learning deficits resulting from frontal and hippocampal ablation in animals of the same species, tested under identical behavioral conditions. A demonstration of the lateralization of the hippocampal effect in one hemisphere of a splitbrain cat will be presented as well. Material
and
Methods
Twelve cats served as subjects. There were three in the hippocampal group, two in the frontal group, and three in the normal control group. TWO cats served as operated controls, having the hippocampus exposed and visualized through a neocortical slit. One cat sustained a bilateral removal of both orbitofrontal cortex and hippocampus. One split-brain preparation (corpus callosum and anterior commissure sectioned) with a unilateral hippocampal ablation was used as well. The cats were trained to depress one of two pedals in a tactile discrimination apparatus described previously by Stamm and Sperry (14). Briefly, two pairs of duplicate pedals were used to randomly alternate the right-left placement of the correct and incorrect stimulus. A correct response was rewarded with a food pellet; an incorrect response resulted in the sounding of a buzzer. A noncorrection procedure was used. Three problems were given in the following order: brush vs flat wood, single bump vs double ,bump (both wood), flat metal vs flat fabric. The cats were given fifty trials a day until their performance reached a criterion of two out of three days at ninety per cent or better. The cats were anesthetized with intrapleural injections of Nembutal (35 mg/kg) and the head secured in a mandible holder. Surgery was performed under aseptic conditions. The orbitofrontal cortex was ablated in a manner described by Warren, Warren and Akert (18). The hippocampal ablations were made in the following manner: After a large bone flap was removed, the duramater was cut and reflected over the other hemisphere. A transverse slit extending from the middle suprasylvian gyrus to the posterior ectosylvian gyrus, penetrating the optic radiations, was made. The edges of the slit were spread apart with a speculum exposing the hippocampus. This structure was visualized through an operating microscope and was then gently aspirated. The wound was packed with bits of thrombin-soaked gelfoam, and the dura mater replaced. The procedure was repeated on the other hemisphere. The bone
454
TEITELBAUM
flap was replaced and secured with sutures extending between the temporal muscles. The operated controls were subjected to identical surgical procedures except that after the hippocampus was exposed and visualized, it was left intact.
FIG.
1.
Whole
brain
photographs
of frontal
(top)
and
operated
control
subject
(bottom).
After completion of behavioral testing,’ the animals were killed perfused with saline and formalin. The brains were photographed, frozen sections were cut at 40 u and stained for cells (cresyl violet) myelin (Weil). Photographs showing the lateral surface of the brain 2 The author wishes to express his thanks to Mr. Robert in behavioral testing and to Mrs. Ruth Johnson for her
and then and of a
Gore, Jr. for his assistance assistance in histology.
DISCRIMINATION
455
LEARNING
frontal (top) and an operated control subject (bottom) are presented in Fig. 1. Note that in the frontal subject, gyrus proreus is completely ablated except for a small remnant just below the cruciate sulcus. The other frontal subject had approximately the same amount of damage to
FIG. 2. Whole of a hippocampal
brain photographs subject.
of the dorsal
and
ventral
surface
of the brain
gyrus proreus with a triangular remnant intact wedged between the olfactory tract and the presylvian sulcus. The olfactory tract was severed in both subjects. Two whole brain photographs showing the dorsal and ventral surface of the brain of the hippocampal subject with the greatest amount of incidental cortical damage are shown in Fig. 2.
456 Figure
TEITELBAUM
3 shows
photomicrographs
of sections
taken
from
an animal
with a bilateral hippocampal lesion and another subject (split-brain) with hippocampal lesion. In no case was the hippocampus coma unilateral pletely
ablated.
Remnants
of the dorsal
and ventral
hippocampus
were
FIG. 3. Photomicrographs of transverse sections through the brains of a cat with a bilateral hippocampal lesion (left) and a cat with a unilateral hippocampal lesion (right).
left intact. The main body of the hippocampus was consistently damaged. Near total degeneration of the fibers of the hippocampal commissureand columns of fornix were found in these subjects. The dorsal tenth of the posterior division of the anterior commissure was found to have degenerated as well. The unilateral hippocampal lesion of the split-brain
DISCRIMINATION
LEARNING
457
subject was similar to the bilateral lesions. Unilateral degeneration of the fimbria and the column of fornix homolateral to the lesion was found. Results
Mean discrimination performance of each group for each problem is shown in Fig. 4. There was considerable overlap between subjects of
iooo-
@-------a N l ----*
8
800 -x
1000-
oc
co-4
oc
WH .*----x
F
-H
.. .. . . .. . . . x F
E
c” s
600-
t\
co I1 a
\
d
400-
s
E 5 gl
400-
200-
4
I I 1 2 PROBLEMS
1 3
4. Mean discrimination performance of the hippocampal (H) and frontal (F) groups. FIG. 5. Mean reversal performance of the normal hippocampal (H) and frontal (F) groups.
E / ‘-.-.-*
200-
0
FIG.
‘. \ %. ‘. ‘.\V
f !s
I
O5
2 ’ PROBLEMS
normal
(N),
(N),
operated
operated
I 3 control
(OC),
control
(OC),
each group; analysis of variance indicates that there was no difference between groups (Kruskal-Wallace test p > 0.05). Although the frontal and hippocampal groups did not differ from controls with regard to discrimination learning, these subjects were decidedly inferior in their ability to reverse their acquired stimulus preferences (Kruskal-Wallace test p < 0.05). This is illustrated in Fig. 5. The frontal and hippocampal groups took more than twice as many trials to reach criterion on reversal than the normal and operated con-
458
TEITELBAUM
N
80
5 10 15 20 SESSIONS
DISCRIMINATION
459
LEARNING
trols. The latter, although not significantly different than normal in reversal performance, did show a slight deficit. This is in accord with the findings of Warren, Warren and Akert (18) who used similar operated controls. Although it was not difficult to distinguish either the frontal or hippocampal cat from controls on the basis of their strategy during reversal, no gross behavioral difference between frontals and hippocampals could be discerned. Figure 6 presents the individual performance curves from reversal of the first problem generated by a normal, frontal and hippocampal cat. Also shown is the performance of a cat with both structures ablated before training. While normal subjects show a rapid rise in correct choices per session, frontal and hippocampal subjects show a characteristic three-phase performance curve. There is an initial slow, incremental rise in correct choices, when the animal is making correct responses less than half the time. In this stage, whenever either preparation makes a correct response, it is to the positive pedal on one side. This is not simply a position habit; if this were the case, the subject would be performing at the fifty per cent level. (The position of the correct pedal is placed on each side on half the trials in random order.) Stage two is a manifestation of a position habit. This phase is of the longest duration. Both frontal and hippocampal subjects seem to be content to work for aperiodic fifty per cent reinforcement for about 500 trials before breaking the position habit and going into stage three, rapid recovery and solution of the problem. It is stressed that these position habits are not seen in either frontal or hippocampal subjects during discrimination training. In the case of the frontal subjects, the pattern of behavior shown in Fig. 6 repeated itself during the following two reversals of different problems. The performance pattern of the hippocampal subjects changed gradually on succeeding reversals. Stage two was of a briefer duration and stage three was lengthened. It is interesting to note that the effects of each lesion in the same animal do not add. This is clearly shown in Fig. 6. A comparison of discrimination learning and reversal of each hemisphere of a split-brain preparation is shown in Fig. 7. After demonstrating that there was no intermanual transfer of Problem 1 and its reversal, FIG.
campal
6. Individual (H), frontal
reversal performance (F), and combined
curves generated hippocampal-frontal
by a normal (N), (HF) cat.
hippo-
TEITELBAUM
460
a unilateral hippocampal lesion was placed in the right hemisphere and performance on Problem 2 was compared. The lesion had little, if any, effect upon discrimination performance, but impaired reversal performance to the same degree as was shown with bilateral lesions. Essentially, the findings regarding the magnitude and specificity of the hippocampal deficit are replicated in this single animal with its built-in control. 100
r
60
PAW
It B L
60
60
?AW
0
IO
20
30
0SESSIONS
20
FIG. 7. Performance curves of the left (top) and right (bottom) hemispheres of a split-brain cat on acquisition and reversal of Problem 1 and Problem 2. Hippocampal lesion placed in right hemisphere prior to training on Problem 2.
Discussion
The data reported here confirm the earlier reports by Settlage, Zable and Harlow ( 13) and Warren, Warren and Akert ( 18) of reversal learning deficits in monkeys and cats with frontal lobe damage. Also the report by Mahut and Cordeau (8) of a deficit resulting from hippocampal damage in the monkey was confirmed.
DISCRIMINATION
LEARNING
461
Of greater theoretical significance is the remarkable degree of similarity between the effects of each lesion. This, together with the finding that an animal with both structures ablated cannot be distinguished from animals with either structure ablated, suggest that both structures are part of one system (with regard to reversal learning) so that it does not matter which particular portion of the system is interrupted to obtain the same effect. A fiber pathway relating these structures have been described by Adey and Meyer ( 1) . References 1.
2.
3.
4.
5. 6.
7. 8. 9.
10.
11. 12.
13.
ADEY, W. R., and M. MEYER. 1952. An experimental study of hippocampal afferent pathways from prefrontal and cingulate areas in the monkey. J. Amt. 86: 58-74. BRADY, J. V. 1958. The paleocortex and behavioral motivation, pp. 193-227. In and Biochemical Bases H. F. Harlow and C. N. Woolsey LEds.1, “Biological of Behavior.” Univ. of Wisconsin Press, Madison, Wisconsin. BUTTER, C. M., M. MISHKIN, and H. E. ROSVOLD. 1963. Conditioning and extinction of a food rewarded response after selective ab!ations of the frontal cortex in Rhesus monkeys. Exptl. Neurol. 7: 65-75. JACOBSON, C. F., J. B. WOLFE, and T. A. JACKSON. 1935. An experimental analysis of the functions of the frontal association area in primates. J. Nervous Mental Disease 33: 1-4. KIMURA, D. 1958. Effects of selective hippocampal damage on avoidance behavior of the rat. Can. J. Psychol. 13: 213-217. LICHTEXSTEIN, P. E. 1950. Studies of anxiety. II. The effects of lobotomy on a feeding inhibition in dogs. J. Camp. Physiol. Psychol. 43: 419-427. Efficacy of the rat’s motor cortex is delayed alternation. LOUCKS, R. B. 1931. J. Comp. Neural. 63: 511-567. 1963. Spatial reversal deficit in monkeys MAHUT, H., and J. P. CORDEHU. with amygdalohippocampal ablations. Exptl. Neural. 7: 426-434. MISHKIN, M. 1957. Effects of small frontal lesions on delayed alternation in monkeys. J. Neurophysiol. 20: 615-622. MORGAN, C. T., and W. M. WOOD. 1943. Cortical localization of symbolic processes in the rat. II. Effect of cortical lesions upon delayed alternation in the rat. J. Neurophysiol. 6: 173-180. ORBACH, J., B. MILNER, and T. RASMUSSEN. 1960. Learning and retention in monkeys after amygdala-hippocampus resection. Arch. Neural. 3: 230-251. ROBERTS, W. W., W. N. DEMBER, and M. BRODWIC’K. 1962. Alternation and exploration in rats with hippocampal lesions. J. Camp. Physiol. Psychol. 55: 695-700. 1948. Problem solution by monSETTLAGE, P., M. ZABLE, and H. F. HARLOW. keys following bilateral removal of the prefrontal areas: VI. Performance on tests requiring contradictory reactions to similar and to identical stimuli. J. Exjtl. Psychol. 33: 30-65.
462 14.
15.
16. 17. 18.
TEITELBAUM
Function of the corpus callosum in STAMM, J. S., and R. W. SPERRY. 1957. contralateral transfer of somesthetic discrimination in cats. J. Comp. Physiol. Psychol. 56: 138-143. STEPIEN, L. S., J. P. CORDEAU, and T. RASMUSSEN. 1960. The effect of temporal lobe and hippocampal lesions on auditory and visual recent memory in monkeys. Brain 83: 470-489. TEITELBAUM, H. 1961. A study of hippocampal function in the rat. Ph.D. Thesis, McGill University, Montreal. TEITELBAUM, H., and P. M. MILNER. 1963. Activity changes following partial hippocampal lesions in rats. J. Comp. Physiol. Psychol. 56: 284.289. WARREN, J. M., H. B. WARREN and K. AKERT. 1962. Orbitofrontal cortical lesions and learning in cats. /. Camp. Nezrrol. 118: 17-42.
i%EUROLOGY
9,
A Comparison Hippocampal Learning
452-462
(1964)
of
Effects
Lesions and
of Biology,
Orbitofrontal
and
Discrimination in the
Cat
TEITELBAUM’
California Received
Upon
Reversal
HERMAN Division
of
Institute January
of Technology,
Pasadena
17, 1961
In contrast to normals and brain-damaged controls, cats with bilateral hippocampal or orbitofrontal lesions are severely impaired in their ability to reverse tactile discrimination problems. These lesions do not interfere with discrimination learning per se, and do not affect the cat’s ability to learn new discrimination problems. Both effects are quantitatively and qualitatively similar. It takes either preparation more than twice as many trials than normal to master a reversal. The effect of removal of both structures in the same animal is not additive. Introduction
Although
the hippocampus and orbitofrontal cortex differ in cytoand in anatomical relations to other neural structures, the behavioral changes which take place after these structures are ablated are remarkably similar. For example, Morgan and Wood (10) and Loucks (7) have shown that rats lacking the frontal pole do not alternate as well as normals. Hippocampal lesions have a similar effect (12). According to Lichtenstein (6), passive avoidance performance is impaired by frontal lesions in dogs. Hippocampal lesions in rats result in an inability to perform passive avoidance tests as well (2, 5, 17). Deficits in delayed response and delayed alternation have been found in monkeys with either lesion (4, 9, 11, 15). Finally, increased response perseveration manifested in tests of extinction and habit reversal, are also seen after each lesion (3, 8, 16, 18, and Webster & Vonieda, unpublished). architecture
1 This investigation was carried out during the tenure of a USPH postdoctoral fellowship, the work being supported by a USPH grant (MH0.3372) to Professor R. W. Sperry. The author’s present address is: Pharmacology Department, Albert Einstein College of Medicine, New York, N. Y. 452
DISCRIMINATION
LEARNING
453
The purpose of the present experiment is to make a direct comparison of the severity and qualitative nature of the reversal learning deficits resulting from frontal and hippocampal ablation in animals of the same species, tested under identical behavioral conditions. A demonstration of the lateralization of the hippocampal effect in one hemisphere of a splitbrain cat will be presented as well. Material
and
Methods
Twelve cats served as subjects. There were three in the hippocampal group, two in the frontal group, and three in the normal control group. TWO cats served as operated controls, having the hippocampus exposed and visualized through a neocortical slit. One cat sustained a bilateral removal of both orbitofrontal cortex and hippocampus. One split-brain preparation (corpus callosum and anterior commissure sectioned) with a unilateral hippocampal ablation was used as well. The cats were trained to depress one of two pedals in a tactile discrimination apparatus described previously by Stamm and Sperry (14). Briefly, two pairs of duplicate pedals were used to randomly alternate the right-left placement of the correct and incorrect stimulus. A correct response was rewarded with a food pellet; an incorrect response resulted in the sounding of a buzzer. A noncorrection procedure was used. Three problems were given in the following order: brush vs flat wood, single bump vs double ,bump (both wood), flat metal vs flat fabric. The cats were given fifty trials a day until their performance reached a criterion of two out of three days at ninety per cent or better. The cats were anesthetized with intrapleural injections of Nembutal (35 mg/kg) and the head secured in a mandible holder. Surgery was performed under aseptic conditions. The orbitofrontal cortex was ablated in a manner described by Warren, Warren and Akert (18). The hippocampal ablations were made in the following manner: After a large bone flap was removed, the duramater was cut and reflected over the other hemisphere. A transverse slit extending from the middle suprasylvian gyrus to the posterior ectosylvian gyrus, penetrating the optic radiations, was made. The edges of the slit were spread apart with a speculum exposing the hippocampus. This structure was visualized through an operating microscope and was then gently aspirated. The wound was packed with bits of thrombin-soaked gelfoam, and the dura mater replaced. The procedure was repeated on the other hemisphere. The bone
454
TEITELBAUM
flap was replaced and secured with sutures extending between the temporal muscles. The operated controls were subjected to identical surgical procedures except that after the hippocampus was exposed and visualized, it was left intact.
FIG.
1.
Whole
brain
photographs
of frontal
(top)
and
operated
control
subject
(bottom).
After completion of behavioral testing,’ the animals were killed perfused with saline and formalin. The brains were photographed, frozen sections were cut at 40 u and stained for cells (cresyl violet) myelin (Weil). Photographs showing the lateral surface of the brain 2 The author wishes to express his thanks to Mr. Robert in behavioral testing and to Mrs. Ruth Johnson for her
and then and of a
Gore, Jr. for his assistance assistance in histology.
DISCRIMINATION
455
LEARNING
frontal (top) and an operated control subject (bottom) are presented in Fig. 1. Note that in the frontal subject, gyrus proreus is completely ablated except for a small remnant just below the cruciate sulcus. The other frontal subject had approximately the same amount of damage to
FIG. 2. Whole of a hippocampal
brain photographs subject.
of the dorsal
and
ventral
surface
of the brain
gyrus proreus with a triangular remnant intact wedged between the olfactory tract and the presylvian sulcus. The olfactory tract was severed in both subjects. Two whole brain photographs showing the dorsal and ventral surface of the brain of the hippocampal subject with the greatest amount of incidental cortical damage are shown in Fig. 2.
456 Figure
TEITELBAUM
3 shows
photomicrographs
of sections
taken
from
an animal
with a bilateral hippocampal lesion and another subject (split-brain) with hippocampal lesion. In no case was the hippocampus coma unilateral pletely
ablated.
Remnants
of the dorsal
and ventral
hippocampus
were
FIG. 3. Photomicrographs of transverse sections through the brains of a cat with a bilateral hippocampal lesion (left) and a cat with a unilateral hippocampal lesion (right).
left intact. The main body of the hippocampus was consistently damaged. Near total degeneration of the fibers of the hippocampal commissureand columns of fornix were found in these subjects. The dorsal tenth of the posterior division of the anterior commissure was found to have degenerated as well. The unilateral hippocampal lesion of the split-brain
DISCRIMINATION
LEARNING
457
subject was similar to the bilateral lesions. Unilateral degeneration of the fimbria and the column of fornix homolateral to the lesion was found. Results
Mean discrimination performance of each group for each problem is shown in Fig. 4. There was considerable overlap between subjects of
iooo-
@-------a N l ----*
8
800 -x
1000-
oc
co-4
oc
WH .*----x
F
-H
.. .. . . .. . . . x F
E
c” s
600-
t\
co I1 a
\
d
400-
s
E 5 gl
400-
200-
4
I I 1 2 PROBLEMS
1 3
4. Mean discrimination performance of the hippocampal (H) and frontal (F) groups. FIG. 5. Mean reversal performance of the normal hippocampal (H) and frontal (F) groups.
E / ‘-.-.-*
200-
0
FIG.
‘. \ %. ‘. ‘.\V
f !s
I
O5
2 ’ PROBLEMS
normal
(N),
(N),
operated
operated
I 3 control
(OC),
control
(OC),
each group; analysis of variance indicates that there was no difference between groups (Kruskal-Wallace test p > 0.05). Although the frontal and hippocampal groups did not differ from controls with regard to discrimination learning, these subjects were decidedly inferior in their ability to reverse their acquired stimulus preferences (Kruskal-Wallace test p < 0.05). This is illustrated in Fig. 5. The frontal and hippocampal groups took more than twice as many trials to reach criterion on reversal than the normal and operated con-
458
TEITELBAUM
N
80
5 10 15 20 SESSIONS
DISCRIMINATION
459
LEARNING
trols. The latter, although not significantly different than normal in reversal performance, did show a slight deficit. This is in accord with the findings of Warren, Warren and Akert (18) who used similar operated controls. Although it was not difficult to distinguish either the frontal or hippocampal cat from controls on the basis of their strategy during reversal, no gross behavioral difference between frontals and hippocampals could be discerned. Figure 6 presents the individual performance curves from reversal of the first problem generated by a normal, frontal and hippocampal cat. Also shown is the performance of a cat with both structures ablated before training. While normal subjects show a rapid rise in correct choices per session, frontal and hippocampal subjects show a characteristic three-phase performance curve. There is an initial slow, incremental rise in correct choices, when the animal is making correct responses less than half the time. In this stage, whenever either preparation makes a correct response, it is to the positive pedal on one side. This is not simply a position habit; if this were the case, the subject would be performing at the fifty per cent level. (The position of the correct pedal is placed on each side on half the trials in random order.) Stage two is a manifestation of a position habit. This phase is of the longest duration. Both frontal and hippocampal subjects seem to be content to work for aperiodic fifty per cent reinforcement for about 500 trials before breaking the position habit and going into stage three, rapid recovery and solution of the problem. It is stressed that these position habits are not seen in either frontal or hippocampal subjects during discrimination training. In the case of the frontal subjects, the pattern of behavior shown in Fig. 6 repeated itself during the following two reversals of different problems. The performance pattern of the hippocampal subjects changed gradually on succeeding reversals. Stage two was of a briefer duration and stage three was lengthened. It is interesting to note that the effects of each lesion in the same animal do not add. This is clearly shown in Fig. 6. A comparison of discrimination learning and reversal of each hemisphere of a split-brain preparation is shown in Fig. 7. After demonstrating that there was no intermanual transfer of Problem 1 and its reversal, FIG.
campal
6. Individual (H), frontal
reversal performance (F), and combined
curves generated hippocampal-frontal
by a normal (N), (HF) cat.
hippo-
TEITELBAUM
460
a unilateral hippocampal lesion was placed in the right hemisphere and performance on Problem 2 was compared. The lesion had little, if any, effect upon discrimination performance, but impaired reversal performance to the same degree as was shown with bilateral lesions. Essentially, the findings regarding the magnitude and specificity of the hippocampal deficit are replicated in this single animal with its built-in control. 100
r
60
PAW
It B L
60
60
?AW
0
IO
20
30
0SESSIONS
20
FIG. 7. Performance curves of the left (top) and right (bottom) hemispheres of a split-brain cat on acquisition and reversal of Problem 1 and Problem 2. Hippocampal lesion placed in right hemisphere prior to training on Problem 2.
Discussion
The data reported here confirm the earlier reports by Settlage, Zable and Harlow ( 13) and Warren, Warren and Akert ( 18) of reversal learning deficits in monkeys and cats with frontal lobe damage. Also the report by Mahut and Cordeau (8) of a deficit resulting from hippocampal damage in the monkey was confirmed.
DISCRIMINATION
LEARNING
461
Of greater theoretical significance is the remarkable degree of similarity between the effects of each lesion. This, together with the finding that an animal with both structures ablated cannot be distinguished from animals with either structure ablated, suggest that both structures are part of one system (with regard to reversal learning) so that it does not matter which particular portion of the system is interrupted to obtain the same effect. A fiber pathway relating these structures have been described by Adey and Meyer ( 1) . References 1.
2.
3.
4.
5. 6.
7. 8. 9.
10.
11. 12.
13.
ADEY, W. R., and M. MEYER. 1952. An experimental study of hippocampal afferent pathways from prefrontal and cingulate areas in the monkey. J. Amt. 86: 58-74. BRADY, J. V. 1958. The paleocortex and behavioral motivation, pp. 193-227. In and Biochemical Bases H. F. Harlow and C. N. Woolsey LEds.1, “Biological of Behavior.” Univ. of Wisconsin Press, Madison, Wisconsin. BUTTER, C. M., M. MISHKIN, and H. E. ROSVOLD. 1963. Conditioning and extinction of a food rewarded response after selective ab!ations of the frontal cortex in Rhesus monkeys. Exptl. Neurol. 7: 65-75. JACOBSON, C. F., J. B. WOLFE, and T. A. JACKSON. 1935. An experimental analysis of the functions of the frontal association area in primates. J. Nervous Mental Disease 33: 1-4. KIMURA, D. 1958. Effects of selective hippocampal damage on avoidance behavior of the rat. Can. J. Psychol. 13: 213-217. LICHTEXSTEIN, P. E. 1950. Studies of anxiety. II. The effects of lobotomy on a feeding inhibition in dogs. J. Camp. Physiol. Psychol. 43: 419-427. Efficacy of the rat’s motor cortex is delayed alternation. LOUCKS, R. B. 1931. J. Comp. Neural. 63: 511-567. 1963. Spatial reversal deficit in monkeys MAHUT, H., and J. P. CORDEHU. with amygdalohippocampal ablations. Exptl. Neural. 7: 426-434. MISHKIN, M. 1957. Effects of small frontal lesions on delayed alternation in monkeys. J. Neurophysiol. 20: 615-622. MORGAN, C. T., and W. M. WOOD. 1943. Cortical localization of symbolic processes in the rat. II. Effect of cortical lesions upon delayed alternation in the rat. J. Neurophysiol. 6: 173-180. ORBACH, J., B. MILNER, and T. RASMUSSEN. 1960. Learning and retention in monkeys after amygdala-hippocampus resection. Arch. Neural. 3: 230-251. ROBERTS, W. W., W. N. DEMBER, and M. BRODWIC’K. 1962. Alternation and exploration in rats with hippocampal lesions. J. Camp. Physiol. Psychol. 55: 695-700. 1948. Problem solution by monSETTLAGE, P., M. ZABLE, and H. F. HARLOW. keys following bilateral removal of the prefrontal areas: VI. Performance on tests requiring contradictory reactions to similar and to identical stimuli. J. Exjtl. Psychol. 33: 30-65.
462 14.
15.
16. 17. 18.
TEITELBAUM
Function of the corpus callosum in STAMM, J. S., and R. W. SPERRY. 1957. contralateral transfer of somesthetic discrimination in cats. J. Comp. Physiol. Psychol. 56: 138-143. STEPIEN, L. S., J. P. CORDEAU, and T. RASMUSSEN. 1960. The effect of temporal lobe and hippocampal lesions on auditory and visual recent memory in monkeys. Brain 83: 470-489. TEITELBAUM, H. 1961. A study of hippocampal function in the rat. Ph.D. Thesis, McGill University, Montreal. TEITELBAUM, H., and P. M. MILNER. 1963. Activity changes following partial hippocampal lesions in rats. J. Comp. Physiol. Psychol. 56: 284.289. WARREN, J. M., H. B. WARREN and K. AKERT. 1962. Orbitofrontal cortical lesions and learning in cats. /. Camp. Nezrrol. 118: 17-42.