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Alternation behavior, spatial discrimination, and reversal after electrocoagulation of the ventral mesencephalic tegmentum in the rat
BEHAVIORAL A N D N E U R A L BIOLOGY 2 6 , 8 1 - 8 8
(1979)
Alternation Behavior, Spatial Discrimination, and Reversal after Electrocoagulation of the Ventral Mesencephalic Tegmentum in the Rat D A N I E L GALEY, ROBERT J A F F A R D , AND M I C H E L L E M O A L
Laboratoire de Psychophysiologie, Institut de Biologie Animale, Universitb de Bordeaux 1, Avenue des Facultbs, 33405 Talence Cedex, France Rats with electrocoagulation of the ventral mesencephalic tegmentum surrounding the interpeduncular nucleus were compared to control rats in various behavioral testing situations such as alternation behavior, spatial discrimination learning, and reversal in a T-maze. Lesioned animals showed disturbances of alternation behavior, impairments in spatial discrimination, acquisition, and retention, and great difficulty in reversing previously learned habits. These defects were not imputable to a deficit in memory processes. They indicate impairment of attentional mechanisms. It appeared that the lesion of this part of the limbic midbrain area provoked a behavioral syndrome similar to that resulting from limbic forebrain lesions.
The limbic midbrain area (LMA) is constituted by a set of cell groups located in the pons and mesencephalon. The LMA had been identified by Nauta (1958) who demonstrated a reciprocal anatomical relation with many limbic forebrain (LF) regions. Most of the fibers which connect the LMA and the LF pass through the VMT surrounding the nucleus interpeduncularis. A lesion made in this region interrupts an important part of the limbic forebrain-midbrain interrelations. Previous investigations (Le Moal, Cardo, & Stinus, 1969; Le Moal, Stinus, & Galey, 1976) have shown that radiofrequency (RF) lesions of this area induced a permanent behavioral syndrome characterized by (i) locomotor hyperactivity and hyperreactivity, (ii) faster acquisition in tests such as active avoidance conditioning in a shuttle box or food-reinforced responses in a Skinner box with a CRF paradigm, and (iii) deficits when the rat had to suppress previously learned or innate responses, e.g., extinction of approach learnings and passive avoidance tasks. These deficits are also described after some LF lesions (Karli, 1968; Isaacson, 1974). Moreover, disappearance of spontaneous alternation in a T-maze and impairment of spatial discrimination learning and reversal are 81 0163-1047/79/050081-08502.00/0 Copyright © 1979 by Academic Press, Inc. All rights of reproduction in any form reserved.
82
GALEY, JAFFARD, AND LE MOAL
typical of the LF lesions (Douglas & Raphelson, 1966; Douglas, 1972). For these reasons, it was interesting to see if the VMT lesions provoke the same deficits.
METHODS
Animals and Surgery Twenty male rats of the Sprague-Dawley strain, 9 weeks old at the beginning of the experiments, were used. They were housed individually in a room kept at a constant temperature (22°C) and maintained on a 12-hr dark:light cycle of 12:12 hr (dark:2000-800). They had free access to food and water. A group of 10 experimental rats received electrocoagulation of VMT under sodium pentobarbital anesthesia (80 mg/kg ip). This stereotaxic operation has already been described (Le Moal et al., 1969). For the 10 controls, surgical procedure was the same except that the current was not delivered.
Apparatus Experiments were carried out in a gray wooden T-maze, made of a start box (32.5 cm long x 14.0 cm wide), a stem (52.5 x 14.0), and two goal boxes (36.0 x 14.0) with walls 21.5 cm high. A guillotine door was placed between the start box and the stem and sliding doors blocked the entrances of both goal boxes. Two 100-W bulbs suspended above the start box and the choice point provided the only illumination.
Behavioral Procedure Immediately after surgery animals were handled daily and placed on ad lib water and diet foot regimens so that their body weight was maintained at 90% of their preoperative value. The experiments began 12 days after surgery. On the following days (Days 12 to 20) animals were tested in the T-maze apparatus. In this situation, they were fed once after the daily session so that they were deprived throughout all testing procedures. Habituation. Two days of preliminary training were given to all animals. For this purpose, they were placed in the choice compartment and allowed to explore the maze for 10 min with doors open and food pellets present in both arms. Alternation behavior. On Day 14 they were tested for alternation with food pellets available in each arm of the maze. A trial began by confining the rat in the start box facing toward the stem for 15 sec. Then the guillotine door was raised and choice latency, i.e., the time spent between leaving the start box and entering into the chosen arm, was measured. The rat was finally maintained 15 sec in the goal box. Then, he was replaced in the start box for 11 successive trials.
VMT LESION AND STIMULUS PROCESSING
83
Spatial discrimination. The same day at the end of the last trial, food pellets were r e m o v e d f r o m the m o s t frequently chosen goal box, and trials were immediately repeated until the rat carried out the criterion of five consecutive correct responses (acquisition). On the following day (Day 15) retention testing was achieved by using the same procedure. Reversal. At the end of the last retention trial (Day 15) food reinforcement p l a c e m e n t was received in the other goal box and the rat training was continued until he attained the criterion of five consecutive correct responses. A discrimination retention followed by a reversal was thus accomplished daily during 6 days, from Day 15 to D a y 20.
Histological Study When behavioral testing was completed, all of the operated rats were killed with an o v e r d o s e of thiopental (sodium pentobarbital). The brain was r e m o v e d , placed in 10% formaldehyde, sliced with a cryostat (80 /zm), and stained with thionine (Nissl) for histological examination of the lesion site.
RESULTS
Alternation Behavior The results summarized in Table 1 show that the controls alternated at 77%, a rate significantly different f r o m chance (X2 = 15.7, p < .001). A total lack of alternation was o b s e r v e d with lesioned animals. These animals alternated at a rate of 40%, not statistically different f r o m chance (X2 = 2.02, p > . 10). As can be seen in Table 1 start and choice latencies were not different between the two groups.
Spatial Discrimination Figure 1 indicates the n u m b e r of trials necessary for performing the two, three, four, or five consecutive correct responses. During the acquisition stage (Day 14) the n u m b e r of trials to achieve the criteria was always TABLE 1 Results of the Alternation Behavior Study
Group Control Lesioned Statistical significance
N 10 10
Spontaneous alternation rate (%)a
Median start latency (sec)
Median choice latency (sec)
77 - 3 40 - 1 p < .001b
1 (1-1.5) 1 (1-1.5) NS
9.5 (5.5-22.5) 6.5 (3.5-40) NS
Mean I SEM. b Mann-Whitney U test:U = 98.5.
84
GALEY, JAFFARD, AND LE MOAL RETENTION DAY 15
ACQUISITION DAY 14 6-
=k
•]
Z
Q ev
5-
t/d
~]
Control Lesioned
4.
!3 i Z
2,
1.
O" 2
4
5
CRITERION (CONSECUTIVE
2
CORRECT RESPONSES )
FIG. 1. Spatial discrimination. Mean numbers of trials to achieve successive criteria of two, three, four, and five consecutive correct responses. *p < .05; **p < .01; ***p < .005 (Mann-Whitney U test).
more important for lesioned rats (for criterion 2 to criterion 5, successively: p < .05; p < .01; p < .005; p < .01; M a n n - W h i t n e y U test). In the same group, comparing the acquisition with the retention test, improvement of performances could be seen the following day (for criterion 2: t = 2.84,p < .05, Student's t test) and, for criteria 2 and 3, they do not differ from controls. In this situation, deficits appeared only for the more severe criteria.
Reversal As can be seen in Fig. 2, whatever the criteria, lesioned animals are inferior to controls in each daily reversal. The results for criterion 1 indicate that they repeatedly persevered toward the previously reinforced side. Moreover, it can be seen that lesioned animals do not learn to reverse their choice as the sessions increase. During the last 3 days (Day 18 to Day 20) after the first non-reinforced trial, only 4 of 30 trials were achieved in the other goal box against 20 of 30 among controls (X~ = 17.7, p < .01). Each reversal session began by a retention of the last spatial discrimination made the previous day. We have examined the first choice of each animal during the 6 testing session days. Thus, 60 observations (6 sessions x 10 rats) were made for each group. In 84% of the observed cases, control animals at first chose the goal box which was last reinforced the previous day (significantly different from chance: Xz = 13.1, p < .001);
VMT LESION AND STIMULUS PROCESSING 1CORRECT
85
RESPONSE
4 ¸
o 3 ¸
o
I.o/
2
e~
5 C O N S E C U T I V E CORRECT
RESPONSES
10-
8-
6-
4-
% %
2-
• control o lesioned O-
DAY 15
16
17
18
19
20
DALLY SESSIONS
Fio. 2. Dailyreversal of spatial discrimination. Mean number of trials to achieve criterion 1 (upper) or 5 (bottom) during the reversal learning (different scales are used for the two criteria). this rate was 75% for lesioned animals (X2 = 6.08, p < .02), showing that control animals as well as lesioned ones exhibited a significant retention of the learning acquired the previous day.
Histological Control Schematic drawings of the lesion placement are represented in Fig. 3. All of the 10 experimental rats whose results were presented in this study had lesions located in the V M T area. Parts of the nucleus interpeduncularis were often damaged.
DISCUSSION The radiofrequency lesion of the VMT provokes (i) disappearance o f the alternation behavior; (ii) deficits in the acquisition of a spatial discrimination task even for a low criterion; (iii) deficits in the retention of
86
GALEY, JAFFARD, AND LE MOAL
J
¢
• I " k . , IVl ~
It"
A 1950~x"~ ~P FIG. 3. Histological control of the VMT-lesioned animals. Electrocoagulated areas are drawn on frontal planes (in part from K6nig & Klippel, 1963). Abbreviations: IP, nucleus interpedunculafis; PCMA, pedunculus corporis mamillaris; DTV, DTD, decussatio tegmenti ventralis and dorsalis; FLM, fasciculus longitudinafis medialis (plate number is indicated below each section).
this test for the more severe criteria; and (iv) permanent impairment in the reversal task where the animals had difficulties, as in spatial discrimination, in maintaining the correct choice. One can actually consider the situation of alternation as an example of exploratory behavior in which the animal's choice is limited to two compartments (Kimble, 1975). Thus, disappearance of alternation behavior in VMT-lesioned animals, could
VMT LESION AND STIMULUS PROCESSING
87
indicate impairment of exploratory functions. G l a n z e r ' s theory (1953) associates the tendancy to alternate with stimulus satiation produced by the recently entered goal arm. Deficit of stimulus processing should therefore be the origin of alternation disturbance in VMT-lesioned animals. This m a y equally explain the impairment in spatial discrimination acquisition. We can separate from these s y m p t o m s the great difficulties in performing the four or five consecutive response criterion in spatial discrimination retention. This result m a y be explained by injury to structures involved in suppression of an unadapted response, as in habituation. During the first trial, in all retention testing situations, the lesioned as well as the control rats significantly chose the last goal b o x reinforced the previous day. This result shows integrity of m e c h a n i s m s permitting correct restitution of the m e m o r y trace. This m a y indicate that lesioned rats are impaired in maintaining the same choice rather than in r e m e m b e r i n g this choice. In other ways, there appeared a deficit in the reversal of the spatial discrimination. Lesioned animals showed an incapacity to suppress rapidly the preceding choice. Impaired discrimination reversal learning appears to be related in part to the inability to inhibit responding to irrelevant cues w h e n faced with changing task d e m a n d s (Douglas & Pribram, 1966; Elias, 1970; K e m b l e & B e c k m a n , 1970). This last result underlines similarities which o c c u r between the hippocampal and V M T lesion effects. The hippocampus is the " g e n e r a t o r " of internal inhibition (Douglas, 1975), and it seems reasonable to assume that impairment of attention, revealed b y alternation behavior and reversal after V M T lesion, indicates a deficit of internal inhibitory processes. In conclusion, the V M T s y n d r o m e taken as a whole presents the major characteristics of m o s t of the deficits resulting from limbic forebrain lesions (Isaacson, 1974). In other words, the medial m e s e n c e p h a l o n should functionally be considered as a part of the limbic mechanisms.
REFERENCES Douglas, R. J. (1972). Pavlovian conditioning and the brain. In R. A. Boakes and M. E. Halliday (Eds.), Inhibition and Learning, pp. 529-565. New York: Academic Press. Douglas, R. J. (1975). The development of hippocampal function: Implications for theory and for therapy. In R. L. Isaacson and K. H. Pribram (Eds.), The Hippocampus, Vol. II, Chapter 11. New York: Plenum. Douglas, R. J., & Pribram, K. H. (1966). Learning and limbic lesions. Neuropsychology, 4, 197-220. Douglas, R. J., & Raphelson, A. C. (1966). Spontaneous alternation and septal lesions. Journal of Comparative and Physiological Psychology, 62, 320-322. Elias, M. F. (1970). Differences in reversal learning between two inbred mouse strains. Psychonomic Sciences, 20, 179-180. Glanzer, M. (1953). Stimulus satiation: An explanation of spontaneous alternation and related phenomena. Psychological Review, 60, 257-268. Isaacson, R. L. (1974). The Limbic System. New York: Plenum.
88
GALEY, JAFFARD, AND LE MOAL
Karli, P. (1968). Syst~me limbique et processus de motivation. Journal de Physiologie, Paris, 60, 3-148. Kemble, E. D., & Beckman, G. J. (1970). Vicarious trial and error following amygdaloid lesions in rats. Neuropsychology, 8, 161-169. Kimble, D. P. (1975). Choice behavior in rats with hippocampal lesions. In R. L. Isaacson and K. H. Pribram (Eds.), The Hippocampus, Vol. II, Chapter 10, New York: Plenum. K6nig, J. F., & Klippel, R. A. (1963). The Rat Brain: A Stereotaxic Atlas o f the Forebrain and Lower Parts o f the Brain Stem. Baltimore: Williams & Wilkins. Le Moal, M., Cardo, B., & Stinus, L. (1969). Influence of ventral mesencephalic lesion on various spontaneous and conditioned behaviors in the rat. Physiology & Behavior, 4, 567-573. Le Moal, M., Stinus, L., & Galey, D. (1976). Radiofrequency lesion of the ventral mesencephalic tegmentum: Neurological and behavioral considerations. Experimental Neurology, 50, 521-535. Nauta, W. J. H. (1958). Hippocampal projections and related neural pathways to the midbrain in the cat. Brain, 81, 319-340.
(1979)
Alternation Behavior, Spatial Discrimination, and Reversal after Electrocoagulation of the Ventral Mesencephalic Tegmentum in the Rat D A N I E L GALEY, ROBERT J A F F A R D , AND M I C H E L L E M O A L
Laboratoire de Psychophysiologie, Institut de Biologie Animale, Universitb de Bordeaux 1, Avenue des Facultbs, 33405 Talence Cedex, France Rats with electrocoagulation of the ventral mesencephalic tegmentum surrounding the interpeduncular nucleus were compared to control rats in various behavioral testing situations such as alternation behavior, spatial discrimination learning, and reversal in a T-maze. Lesioned animals showed disturbances of alternation behavior, impairments in spatial discrimination, acquisition, and retention, and great difficulty in reversing previously learned habits. These defects were not imputable to a deficit in memory processes. They indicate impairment of attentional mechanisms. It appeared that the lesion of this part of the limbic midbrain area provoked a behavioral syndrome similar to that resulting from limbic forebrain lesions.
The limbic midbrain area (LMA) is constituted by a set of cell groups located in the pons and mesencephalon. The LMA had been identified by Nauta (1958) who demonstrated a reciprocal anatomical relation with many limbic forebrain (LF) regions. Most of the fibers which connect the LMA and the LF pass through the VMT surrounding the nucleus interpeduncularis. A lesion made in this region interrupts an important part of the limbic forebrain-midbrain interrelations. Previous investigations (Le Moal, Cardo, & Stinus, 1969; Le Moal, Stinus, & Galey, 1976) have shown that radiofrequency (RF) lesions of this area induced a permanent behavioral syndrome characterized by (i) locomotor hyperactivity and hyperreactivity, (ii) faster acquisition in tests such as active avoidance conditioning in a shuttle box or food-reinforced responses in a Skinner box with a CRF paradigm, and (iii) deficits when the rat had to suppress previously learned or innate responses, e.g., extinction of approach learnings and passive avoidance tasks. These deficits are also described after some LF lesions (Karli, 1968; Isaacson, 1974). Moreover, disappearance of spontaneous alternation in a T-maze and impairment of spatial discrimination learning and reversal are 81 0163-1047/79/050081-08502.00/0 Copyright © 1979 by Academic Press, Inc. All rights of reproduction in any form reserved.
82
GALEY, JAFFARD, AND LE MOAL
typical of the LF lesions (Douglas & Raphelson, 1966; Douglas, 1972). For these reasons, it was interesting to see if the VMT lesions provoke the same deficits.
METHODS
Animals and Surgery Twenty male rats of the Sprague-Dawley strain, 9 weeks old at the beginning of the experiments, were used. They were housed individually in a room kept at a constant temperature (22°C) and maintained on a 12-hr dark:light cycle of 12:12 hr (dark:2000-800). They had free access to food and water. A group of 10 experimental rats received electrocoagulation of VMT under sodium pentobarbital anesthesia (80 mg/kg ip). This stereotaxic operation has already been described (Le Moal et al., 1969). For the 10 controls, surgical procedure was the same except that the current was not delivered.
Apparatus Experiments were carried out in a gray wooden T-maze, made of a start box (32.5 cm long x 14.0 cm wide), a stem (52.5 x 14.0), and two goal boxes (36.0 x 14.0) with walls 21.5 cm high. A guillotine door was placed between the start box and the stem and sliding doors blocked the entrances of both goal boxes. Two 100-W bulbs suspended above the start box and the choice point provided the only illumination.
Behavioral Procedure Immediately after surgery animals were handled daily and placed on ad lib water and diet foot regimens so that their body weight was maintained at 90% of their preoperative value. The experiments began 12 days after surgery. On the following days (Days 12 to 20) animals were tested in the T-maze apparatus. In this situation, they were fed once after the daily session so that they were deprived throughout all testing procedures. Habituation. Two days of preliminary training were given to all animals. For this purpose, they were placed in the choice compartment and allowed to explore the maze for 10 min with doors open and food pellets present in both arms. Alternation behavior. On Day 14 they were tested for alternation with food pellets available in each arm of the maze. A trial began by confining the rat in the start box facing toward the stem for 15 sec. Then the guillotine door was raised and choice latency, i.e., the time spent between leaving the start box and entering into the chosen arm, was measured. The rat was finally maintained 15 sec in the goal box. Then, he was replaced in the start box for 11 successive trials.
VMT LESION AND STIMULUS PROCESSING
83
Spatial discrimination. The same day at the end of the last trial, food pellets were r e m o v e d f r o m the m o s t frequently chosen goal box, and trials were immediately repeated until the rat carried out the criterion of five consecutive correct responses (acquisition). On the following day (Day 15) retention testing was achieved by using the same procedure. Reversal. At the end of the last retention trial (Day 15) food reinforcement p l a c e m e n t was received in the other goal box and the rat training was continued until he attained the criterion of five consecutive correct responses. A discrimination retention followed by a reversal was thus accomplished daily during 6 days, from Day 15 to D a y 20.
Histological Study When behavioral testing was completed, all of the operated rats were killed with an o v e r d o s e of thiopental (sodium pentobarbital). The brain was r e m o v e d , placed in 10% formaldehyde, sliced with a cryostat (80 /zm), and stained with thionine (Nissl) for histological examination of the lesion site.
RESULTS
Alternation Behavior The results summarized in Table 1 show that the controls alternated at 77%, a rate significantly different f r o m chance (X2 = 15.7, p < .001). A total lack of alternation was o b s e r v e d with lesioned animals. These animals alternated at a rate of 40%, not statistically different f r o m chance (X2 = 2.02, p > . 10). As can be seen in Table 1 start and choice latencies were not different between the two groups.
Spatial Discrimination Figure 1 indicates the n u m b e r of trials necessary for performing the two, three, four, or five consecutive correct responses. During the acquisition stage (Day 14) the n u m b e r of trials to achieve the criteria was always TABLE 1 Results of the Alternation Behavior Study
Group Control Lesioned Statistical significance
N 10 10
Spontaneous alternation rate (%)a
Median start latency (sec)
Median choice latency (sec)
77 - 3 40 - 1 p < .001b
1 (1-1.5) 1 (1-1.5) NS
9.5 (5.5-22.5) 6.5 (3.5-40) NS
Mean I SEM. b Mann-Whitney U test:U = 98.5.
84
GALEY, JAFFARD, AND LE MOAL RETENTION DAY 15
ACQUISITION DAY 14 6-
=k
•]
Z
Q ev
5-
t/d
~]
Control Lesioned
4.
!3 i Z
2,
1.
O" 2
4
5
CRITERION (CONSECUTIVE
2
CORRECT RESPONSES )
FIG. 1. Spatial discrimination. Mean numbers of trials to achieve successive criteria of two, three, four, and five consecutive correct responses. *p < .05; **p < .01; ***p < .005 (Mann-Whitney U test).
more important for lesioned rats (for criterion 2 to criterion 5, successively: p < .05; p < .01; p < .005; p < .01; M a n n - W h i t n e y U test). In the same group, comparing the acquisition with the retention test, improvement of performances could be seen the following day (for criterion 2: t = 2.84,p < .05, Student's t test) and, for criteria 2 and 3, they do not differ from controls. In this situation, deficits appeared only for the more severe criteria.
Reversal As can be seen in Fig. 2, whatever the criteria, lesioned animals are inferior to controls in each daily reversal. The results for criterion 1 indicate that they repeatedly persevered toward the previously reinforced side. Moreover, it can be seen that lesioned animals do not learn to reverse their choice as the sessions increase. During the last 3 days (Day 18 to Day 20) after the first non-reinforced trial, only 4 of 30 trials were achieved in the other goal box against 20 of 30 among controls (X~ = 17.7, p < .01). Each reversal session began by a retention of the last spatial discrimination made the previous day. We have examined the first choice of each animal during the 6 testing session days. Thus, 60 observations (6 sessions x 10 rats) were made for each group. In 84% of the observed cases, control animals at first chose the goal box which was last reinforced the previous day (significantly different from chance: Xz = 13.1, p < .001);
VMT LESION AND STIMULUS PROCESSING 1CORRECT
85
RESPONSE
4 ¸
o 3 ¸
o
I.o/
2
e~
5 C O N S E C U T I V E CORRECT
RESPONSES
10-
8-
6-
4-
% %
2-
• control o lesioned O-
DAY 15
16
17
18
19
20
DALLY SESSIONS
Fio. 2. Dailyreversal of spatial discrimination. Mean number of trials to achieve criterion 1 (upper) or 5 (bottom) during the reversal learning (different scales are used for the two criteria). this rate was 75% for lesioned animals (X2 = 6.08, p < .02), showing that control animals as well as lesioned ones exhibited a significant retention of the learning acquired the previous day.
Histological Control Schematic drawings of the lesion placement are represented in Fig. 3. All of the 10 experimental rats whose results were presented in this study had lesions located in the V M T area. Parts of the nucleus interpeduncularis were often damaged.
DISCUSSION The radiofrequency lesion of the VMT provokes (i) disappearance o f the alternation behavior; (ii) deficits in the acquisition of a spatial discrimination task even for a low criterion; (iii) deficits in the retention of
86
GALEY, JAFFARD, AND LE MOAL
J
¢
• I " k . , IVl ~
It"
A 1950~x"~ ~P FIG. 3. Histological control of the VMT-lesioned animals. Electrocoagulated areas are drawn on frontal planes (in part from K6nig & Klippel, 1963). Abbreviations: IP, nucleus interpedunculafis; PCMA, pedunculus corporis mamillaris; DTV, DTD, decussatio tegmenti ventralis and dorsalis; FLM, fasciculus longitudinafis medialis (plate number is indicated below each section).
this test for the more severe criteria; and (iv) permanent impairment in the reversal task where the animals had difficulties, as in spatial discrimination, in maintaining the correct choice. One can actually consider the situation of alternation as an example of exploratory behavior in which the animal's choice is limited to two compartments (Kimble, 1975). Thus, disappearance of alternation behavior in VMT-lesioned animals, could
VMT LESION AND STIMULUS PROCESSING
87
indicate impairment of exploratory functions. G l a n z e r ' s theory (1953) associates the tendancy to alternate with stimulus satiation produced by the recently entered goal arm. Deficit of stimulus processing should therefore be the origin of alternation disturbance in VMT-lesioned animals. This m a y equally explain the impairment in spatial discrimination acquisition. We can separate from these s y m p t o m s the great difficulties in performing the four or five consecutive response criterion in spatial discrimination retention. This result m a y be explained by injury to structures involved in suppression of an unadapted response, as in habituation. During the first trial, in all retention testing situations, the lesioned as well as the control rats significantly chose the last goal b o x reinforced the previous day. This result shows integrity of m e c h a n i s m s permitting correct restitution of the m e m o r y trace. This m a y indicate that lesioned rats are impaired in maintaining the same choice rather than in r e m e m b e r i n g this choice. In other ways, there appeared a deficit in the reversal of the spatial discrimination. Lesioned animals showed an incapacity to suppress rapidly the preceding choice. Impaired discrimination reversal learning appears to be related in part to the inability to inhibit responding to irrelevant cues w h e n faced with changing task d e m a n d s (Douglas & Pribram, 1966; Elias, 1970; K e m b l e & B e c k m a n , 1970). This last result underlines similarities which o c c u r between the hippocampal and V M T lesion effects. The hippocampus is the " g e n e r a t o r " of internal inhibition (Douglas, 1975), and it seems reasonable to assume that impairment of attention, revealed b y alternation behavior and reversal after V M T lesion, indicates a deficit of internal inhibitory processes. In conclusion, the V M T s y n d r o m e taken as a whole presents the major characteristics of m o s t of the deficits resulting from limbic forebrain lesions (Isaacson, 1974). In other words, the medial m e s e n c e p h a l o n should functionally be considered as a part of the limbic mechanisms.
REFERENCES Douglas, R. J. (1972). Pavlovian conditioning and the brain. In R. A. Boakes and M. E. Halliday (Eds.), Inhibition and Learning, pp. 529-565. New York: Academic Press. Douglas, R. J. (1975). The development of hippocampal function: Implications for theory and for therapy. In R. L. Isaacson and K. H. Pribram (Eds.), The Hippocampus, Vol. II, Chapter 11. New York: Plenum. Douglas, R. J., & Pribram, K. H. (1966). Learning and limbic lesions. Neuropsychology, 4, 197-220. Douglas, R. J., & Raphelson, A. C. (1966). Spontaneous alternation and septal lesions. Journal of Comparative and Physiological Psychology, 62, 320-322. Elias, M. F. (1970). Differences in reversal learning between two inbred mouse strains. Psychonomic Sciences, 20, 179-180. Glanzer, M. (1953). Stimulus satiation: An explanation of spontaneous alternation and related phenomena. Psychological Review, 60, 257-268. Isaacson, R. L. (1974). The Limbic System. New York: Plenum.
88
GALEY, JAFFARD, AND LE MOAL
Karli, P. (1968). Syst~me limbique et processus de motivation. Journal de Physiologie, Paris, 60, 3-148. Kemble, E. D., & Beckman, G. J. (1970). Vicarious trial and error following amygdaloid lesions in rats. Neuropsychology, 8, 161-169. Kimble, D. P. (1975). Choice behavior in rats with hippocampal lesions. In R. L. Isaacson and K. H. Pribram (Eds.), The Hippocampus, Vol. II, Chapter 10, New York: Plenum. K6nig, J. F., & Klippel, R. A. (1963). The Rat Brain: A Stereotaxic Atlas o f the Forebrain and Lower Parts o f the Brain Stem. Baltimore: Williams & Wilkins. Le Moal, M., Cardo, B., & Stinus, L. (1969). Influence of ventral mesencephalic lesion on various spontaneous and conditioned behaviors in the rat. Physiology & Behavior, 4, 567-573. Le Moal, M., Stinus, L., & Galey, D. (1976). Radiofrequency lesion of the ventral mesencephalic tegmentum: Neurological and behavioral considerations. Experimental Neurology, 50, 521-535. Nauta, W. J. H. (1958). Hippocampal projections and related neural pathways to the midbrain in the cat. Brain, 81, 319-340.