A generalized learning deficit in albino rats with early median raphe or pontine reticular formation lesions

Physiology & Behavior, Vol. 32, pp. 107-114.Copyright ©PergamonPress Ltd., 1984. Printed in the U.S.A.

0031-9384/84$3.00 + .00

A Generalized Learning Deficit in Albino Rats with Early Median Raphe or Pontine Reticular Formation Lesions ROBERT THOMPSON, 2 ANDROULLA

RAMSAY AND JEN YU

Fairview State Hospital, Costa Mesa, CA 92626 and Department o f Physical Medicine and Rehabilitation University o f California lrvine Medical Center, I01 City Drive South Orange, CA 92668 R e c e i v e d 23 J u n e 1983 THOMPSON, R., A. RAMSAY AND J. YU. A generalized learning deficit in albino rats with early median raphe or pontine reticularformation lesions. PHYSIOL BEHAV 32(1) 107-114, 1984.--Recent studies suggest that lesions of the median raphe or pontine reticular formation in adult rats are associated with a nonspecific (generalized) learning impairment. The present study showed that lesions in the region of the median raphe or pontine reticular formation in 21 day old rats likewise produced a nonspecific learning impairment, as evidence by significant deficits on a visual discrimination, nonvisual incline plane discrimination, 3-cul maze, and three simple spatial problems. The finding that relatively large lateral pontomesencephalic Lesionsdid not lead to deficient learning of any of these tasks indicates that lesion locus rather than lesion size is responsible for the production of the learning deficits observed in this study. Median raphe lesions Pontine reticular formation lesions Generalized learning deficit THE area of the median raphe (MR) and the medial portions of the pontine reticular formation (PRF) are two regions of the brainstem that may play a nonspecific role in the learning process in the laboratory rat. This suggestion is based on the recent findings that localized damage to either one of these regions in adult rats leads to deficient learning of both visual and nonvisual discrimination habits [9]. Parenthetically, adult rats with discrete lesions to those brain regions most frequently cited in connection with learning (cerebral cortex, hippocampus, mamillary bodies, and mediodorsal thalamus) have not been found to exhibit a nonspecific learning impairment [8]. The present study was undertaken to determine whether selective lesions to the region of the MR or PRF in weanling (21 day old) rats would likewise produce a nonspecific (generalized) learning deficit. Such a finding would be of considerable interest since there appear to be no reports in the experimental literature that a discrete brain lesion induced relatively early in life will lead to generalized learning loss. Two sets of laboratory tasks were used, one involving the aversive motive of escape-avoidance of foot shock (Experiment 1), and the second involving the appetitive motive of thirst (Experiment 2). The former set included a white-black discrimination, a nonvisual incline plane discrimination, and a 3-cul maze. The latter set consisted of three simple spatial problems, each of which could be mastered within a few trials by sham-operated rats.

Discrimination learning

Maze learning

As a control for any nonspecific debilitating effects arising from brainstem damage, weanling rats with lesions to the lateral portions of the brainstem at pontomesencephalic levels (LPA) were also studied. (This region of the brainstem has not been found to be critical for the expression of previously learned visual or nonvisual discrimination habits in the adult rat [7].) EXPERIMENT 1 METHOD

Subjects and Surgery Forty-seven weanling (21 day old) male Sprague-Dawley albino rats, 36-50 g, underwent surgery under deep chloral hydrate anesthesia (400 mg/kg). All lesions were accomplished electrolytically by passing a constant anodal current of 1.0-1.3 mA for a duration of 8-10 sec through an implanted stainless steel electrode (0.5 mm in dia.) with 1.0 mm of the tip exposed. One group (Group MR) sustained a single midline lesion to the median raphe, the second (Group PRF) received bilateral lesions (1.0 mm lateral to the midline) to the pontine reticular formation, and the third (Group LPA) was subjected to bilateral lesions (1.9 mm lateral to the midline) to the lateral pontomesencephalic area. (The anterior and ventral coordinates were the same for all g r o u p s - - l . 5 mm rostral to lambda and 7.5 mm below the

tThe completion of this research was facilitated by a grant from the Rehabilitation Center for Brain Dysfunction. 2Requests for reprints should be addressed to: Robert Thompson, Fairview State Hospital, Costa Mesa, CA 92626.

107

108 surface of the dura--based upon the Thompson rat atlas [7].) A fourth group (Group C) served as sham-operated controls, undergoing the same surgical procedure as the experimental groups, save for insertion of the lesion electrode and the application of current. Throughout the recovery period, the animals were handled for approximately 5 min on every third day. Preliminary training began 3 weeks after surgery. On the day prior to preliminary training, the vibrissae of each animal were shaved -(see [8]).

Apparatus Visual discrimination. A two-choice Thompson-Bryant discrimination box, utilizing the motive of escape-avoidance of foot shock (l.0-1.5 mA), was employed (see [7]). Two pairs of stimulus cards mounted on wooden blocks were used in the apparatus. One pair (two medium grey cards) was employed in training the animals to push aside a card in order to gain access to the goal box. The second pair consisted of a white card and a black card. Incline plane discrimination. A single unit T-maze, modified for the use of the escape-avoidance of foot shock motive (1.0-1.5 mA), was employed to establish the incline plane (vestibular-proprioceptive-kinesthetic) discrimination habit (see [7]). This maze was secured to a platform which could be tilted I 1° laterally. Maze. A 3-cul maze, utilizing the motive of escapeavoidance of foot shock (1.0-1.5 mA), was employed (see [7]). The true path, which measured 120.5 cm in length from the start box exit to the goal box entrance, consisted of a 90° turn to the left (avoiding the first cul), a 180° turn to the right (avoiding the second and third culs), followed by a 90° turn to the left. The apparatus was located in a sound-attenuated room that was illuminated by conventional ceiling fluorescent lights. No effort was made to control for intramaze olfactory cues of any extramaze cues.

Procedure All subjects were initially required to learn the visual discrimination problem. Following learning, approximately half of the animals from each group were then trained on the incline plane discrimination problem. The remaining animals from each group that learned the visual problem were rested until they were 90 days old and subsequently were trained on the 3-cul maze habit. Throughout the experiment, the animals were run " b t i n d " - - t h e experimenter had no knowledge as to which group each subject belonged. Visual discrimination.On Day 1, each rat was allowed to explore the goal box for 10 min. The windows were blocked during this time to prevent the animal from entering the choice chamber. Subsequently, the rat was placed in a restraining cage for 10 min after which it was returned to the home cage. On Day 2, each rat was trained to run into the choice chamber from the start box, displace one of the cards blocking the window, and enter the goal box in order to escape from (or avoid) foot shock. On Day 3, training on the brightness discrimination was begun. An approach response to the unlocked white card (positive) admitted the animal to the goal box. On the other hand, an approach response to the adjacent locked black card (negative) was punished by foot shock, the animal sub-

THOMPSON, RAMSAY AND YU sequently being forced to respond to the white card in order to gain entrance into the goal box. An error was defined as an approach response to the black card which brought the animal's forefeet in contact with the charged grid section which extended 8.0 cm in front of the negative card. The position of the positive (and negative) card was switched from the right to the left window in a sequence mixed with single- and doublealternation runs. Usually, 8-10 trials were given each day with an intertrial interval of 50-75 sec. The criterion of learning consisted of the first appearance of either a "perfect" or ~'near-perfect'" run of correct responses have a probability of occurrence of 0.05 [3], followed by at least 75% correct responses in the subsequent block of 8 trials given on the next day. In a few instances, the criterion was not reached within 100 trials, but the animals (and their respective trial and error scores) were treated as though the criterion was met on the one-hundredth trial. The specific training procedure was as follows: The animal was placed in the start box and the start box door was raised. Failure to leave the start box within 5 sec was followed by foot shocks until the animal entered the choice chamber. No further toot shocks were administered unless the animal made an error or failed to respond to one of the cards within 5 sec. The animal was allowed to remain in the goal box for 10 sec, after which it was transferred to the restraining cage to await the next trial. The animals were usually run in squads of two. Incline plane discrimination. Those animals designated to learn this problem were first habituated to each end box for 5 rain and then were trained to run into one of the arms from the start box, displace the card blocking the window, and enter the end box in order to escape from (or avoid) foot shock. During this period, the apparatus was in the horizontal position. One hour later, the animals were blinded by enucleation under deep chloral hydrate anesthesia. On the following day, the animals were trained on the incline plane discrimination--an approach response to the upward sloping arm led to an end box which could be entered by displacing the unlocked card, whereas an approach response to the downward sloping arm led to a locked card preventing the animal from entering the end box on that side. Punishment for an error (approach to within 10.8 ~m of the locked card) was given by charging the grid section located below the locked card. The position of the correct (and incorrect) arm was switched from the right to the left side in a sequence mixed with single- and double-alternation runs and 8-10 trials were usually given each day with an intertrial interval of 50-75 sec. The criterion of learning and the specific training procedure were the same as those described for the visual discrimination task. Maze. Each animal assigned to the maze problem was first habituated to the goal box for 5 min. Subsequently, it was placed in the start box and the start box door was raised. Failure to leave the start box within 5 sec was followed by foot shocks. No further foot shocks were given unless the animal made an error (entered a blind alley by at least the length of its head and thorax) or stopped forward progression in the maze. Upon entering the goal box, a guillotine door was lowered to prevent reentry into the maze. The animal was permitted to remain in the goal box for 10 sec, after which it was transferred to the restraining cage to await the next trial. Four trials were given daily with an intertrial interval of 50-75 sec. Training was terminated when the animal made no more than one error in two consecutive days or failed to attain this criterion within 10 days.

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TABLE 1 MEAN LEARNING(TRIALSAND ERRORS)SCORES FOR ALL GROUPS Trials Group

N

Mean

Initial Errors

Range

Mean

Total Errors

Range

Mean

Range

I 1-30 34-49 32-56 13-20

24.0 55.5* 54.3* 21.0

17-40 41-67 32-64 14-27

6-14 14-42 23-48 8-9

11.0 25.2* 37.0* 10.0

9-15 15-42 23-50 9-12

3-12 37-71 13-42 4-9

9.0 60.0* 43.3* 7.0

5-14 40°83 19-56 4-10

Visual Discrimination C MR PRF LPA

24 8 8 7

38.0 92.9* 90.0* 32.2

21-60 78-100 61-100 25-48

C MR PRF LPA

12 4 4 4

17.7 56.0* 74.5* 13.5

10-36 29-100 48-100 12-15

18.4 42.8* 45.0* 17.8

Incline Plane Discrimination 9.2 20.5* 35.8* 8.1 Maze C MR PRF LPA

12 4 4 3

5.5 40.0* 30.0* 5.3

4-8 12-40 4-8

7.0 50.5* 32.3* 6.3

*Differs from sham controls, Mann-Whitney U, p<0.01.

Histology At the conclusion of postoperative training, each braindamaged rat was killed with an overdose of chloral hydrate, its vascular system perfused with normal saline followed by 10% formalin, and the brain removed and stored in 10% formalin for 2-4 days. Each brain was then blocked, frozen, and sectioned frontally at 90 microns. Every fourth section through the lesioned area was retained and subsequently photographed at 12× by using the section as a negative film in an enlarger (see [7]).

Measures of Performance Performance measures consisted of both trials to criterion and initial errors to criterion. A third measure (total errors to criterion) was also included because it was not uncommon for an animal to commit multiple (repetitive) errors within a given trial. In the case of the discrimination problems, multiple errors occurred when the animal retreated from the charged grid section below the locked card and then approached the locked card a second (third, fourth, etc.) time, each approach response resulting in foot shock. With respect to the maze, multiple errors occurred when the animal reentered any one of the three blind alleys. Thus, total errors to criterion involved the sum of approaches to the locked card (or blind alleys) that resulted in foot shock. The differences in mean performance scores between each brain-damaged group and the controls were evaluated by the Mann-Whitney U test (two-tailed), corrected for ties. RESULTS

Learning Table 1 summarized the mean performance scores for all

groups on the visual, incline plane and maze problems. These results will be discussed in terms of the site of the brain damage. Group C. All sham-operated controls succeeded in reaching the criterion of learning on the visual problem within 60 trials (excluding the criterion run), on the incline plane problem within 36 trials, and on the maze problem within 8 trials. In terms of trials to criterion, the Wilcoxon test disclosed that the visual problem was significantly more difficult to master than either the incline plane or maze problem and that the incline plane problem was significantly more difficult to master than the maze problem (ps<0.01). These findings, however, are to be interpreted with caution since the order of presentation of the problems was not counterbalanced. Group MR. All eight rats suffered varying amounts of damage to the MR. In most cases, such as the one shown in Fig. 1, the lesions began dorsal to the interpeduncular nucleus and extended caudally into the MR. In the remaining cases, the lesions began at the rostral portion of the MR and extended posteriorly to the level of the dorsal tegmental nucleus of Gudden. (There appeared to be no clear-cut differences in performance scores as a function of the anteriorposterior placements of the lesions.) As shown in Table 1, this group was significantly inferior to the controls on each of the three problems. Five of the eight animals failed to learn the visual problem within 100 trials, two of the four animals failed to learn the incline plane problem within 100 trials, and none of the four animals learned the maze problem within 40 trials. Only one animal succeeded in learning both the first (visual) and the second (incline plane) problem within the limits of training; this animal suffered the smallest MR lesion of the group. Group PRF. Half of the animals of this group sustained lesions to the PRF similar to the one shown in Fig. 2, while

II0

FIG. 1. Unstained sections showing a lesion of the MR in one an i mal.

THOMPSON,

RAMSAY

A N D YU

FIG. 2. Unstained sections showing a lesion t~f ~he PRF in ~)ne ~tnimal,

G E N E R A L I Z E D L E A R N I N G DEFICIT

111

the remaining half had somewhat more medially placed lesions which encroached upon the ventral tegmental nucleus of Gudden. There was a suggestion that the medial lesions tended to produce greater performance deficits than the lateral lesions, but none of the differences in performance scores approached statistical significance. Table 1 shows that this group, like Group MR, was significantly impaired in learning each of the three problems. Five of the eight animals failed to learn the visual problem, two of the four animals failed to learn the incline plane problem, and two of the four animals failed to learn the maze problem within the limits of training. Only one animal succeeded in mastering both the first (visual) and the second (incline plane) problem; this animal suffered the only lesion that was appreciably asymmetrical in the lateral plane. Group LPA. All seven animals of this group sustained lesions to the far-lateral pontomesencephalic region like the one shown in Fig. 3. In contrast to the other two braindamaged groups, this group tended to learn each of the three problems somewhat faster than the controls, but the differences in performance scores were far from being statistically significant.

Other Observations Body weight. At 42 days of age, Group C weighed significantly more than each of the experimental groups (ps<0,05), the mean weights being 164+4 g (Group C), 124-+9 g (Group MR), 141+8 g (Group PRF), and 114_+13 g (Group LPA). Virtually the same pattern of results was observed at 90 days of age in those subgroups tested on the maze problem, their mean weights being 352+ 13 g (Group C), 226-+27 g (Group MR), 282_+32 g (Group PRF), and 233-+ 16 g (Group LPA). General health. Except for being appreciably smaller than the controls, all brain-damaged animals appeared healthy and alert at the time of the visual discrimination test. When examined at the end of the first post-operative week, the majority of rats from Groups MR and PRF exhibited a defective labyrinthine reflex (retroflexion of the head when suspended by its tail). While none of the animals from Group LPA exhibited a defective labyrinthine reflex, four showed a "tremor at rest" of the head in the horizontal and/or vertical plane (this finding confLrms earlier observations [7]) and three showed hyperextension of the forelegs during locomotion. (Activity was not tested, but see Experiment 2.) Escape-avoidance behavior. All of the controls and most of the brain-damaged animals readily entered the choice chamber (or maze proper) from the start box and proceeded toward the goal box (or end box) either without foot shock or with the application of one or two foot shocks. Only one animal from Group MR, two from Group PRF, and one from Group LPA required more than the usual number of foot shocks to force escape responses and this occurred only during the first few days of training on the visual discrimination problem. A more frequently observed "aberrant" escapeavoidance response (which appeared mainly in the visual discrimination apparatus) consisted of extremely rapid (ballistic) running from the start box toward the goal box. This was seen in 16 control rats and in seven brain-damaged rats (four from Group MR, two from Group PRF, and one from Group LPA). By routinely imposing a delay of 10-20 sec between inserting the animal into the start box and raising the start box door, it was possible to reduce running speed in these animals. (Though not significant, the fast runners

FIG. 3. Unstained sections showing a lesion of the LPA in one animal.

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THt)MPSON, RAMSAY AND YI. none of the three MR subjects and three of the five PRF subjects succeeded in learning the white-black discrimination within 100 trials [9]. In the weanling rats studied in Experiment I, three of the eight MR subjects and three of the eight PRF subjects succeeded in learning the same discrimination within 100 trials. (It is likely that a similar pattern of results would be obtained in relation to acquisition of the incline plane and maze problems in light of the findings that at least 75% of adult rats with MR or PRF lesions exhibit severe relearning disturbances--errors to relearn postoperatively being greater than errors to learn preoperatively--on these tasks [7].) Although the deficits in acquisition of these aversively motivated tasks suggest that relatively early (or late) lesions of the MR or PRF produced a generalized learning impairment, the possibility exists that similarly placed lesions within the brainstem of weanling rats may not impair acquisition of certain appetitively motivated tasks. Some support for this possibility comes from the findings that adult rats with MR lesions are not deficient in learning simple foodreinforced T-maze discrimination habits [1]. Experiment 2 was therefore carried out to determine whether weanling rats subjected to either MR or PRF lesions would learn a series of simple spatial tasks reinforced by water (and sweetened wet mash) as fast as sham-operated controls.

EXPERIMENT 2 METHOD

Subjects and Surgery FIG. 4. Schematic drawing of the apparatus used for the appetitive tasks showing the start box (SB), choice chamber (CC), and goal box (GB). The dotted lines mark the boundaries of the "blind alleys." On Problem A (top panel), the rat must turn to the right and proceed between the end of the partition and the wall in order to gain access to the goal box. On Problem B (middle panel), the animal must climb onto the platform to reach the goal box. On Problem C (bottom panel), the animal must turn toward (and enter) the hole in the platform after passing the vertical barrier to reach the goal box.

from each group tended to require more trials to reach the criterion of learning than the respective slow runners.) DISCUSSION

The results of this experiment clearly show that lesions of the MR or PRF in weanling rats produce dramatic learning disturbances on both visual and nonvisual discrimination tasks as well as a 3-cul maze habit. Nonspecific effects arising from brainstem damage cannot readily account for this "generalized" learning impairment since the group with LPA lesions earned excellent performance scores on all three problems, despite sustaining lesions of greater magnitude than the former two groups. While it was not the purpose of the present study to compare early MR or PRF lesions with late (adult) MR or PRF lesions on learning, it is instructive to note that acquisition of the visual discrimination habit (the only common task studied in connection with early and late lesions of the MR and PRF) appears to be drastically impaired whether the lesions are produced in weanling or adult rats. In adult rats,

Twenty-seven weanling (21 day old) Sprague-Dawley male albino rats, 34--50 g, underwent sham operations (Group C), or sustained lesions to either the MR (Group MR), PRF (Group PRF), or LPA (Group LPA) under deep chloral hydrate anesthesia. The procedures concerning surgery, postoperative care, and handling were the same as those described in Experiment I.

Apparatus The learning apparatus was divided into a start box (22.0x38.0x26.5 cm) painted flat white, choice chamber (59.5x38.0x26.5 cm) painted flat white, the goal box (29.5x38.0x26.5 cm) painted flat black. The former two compartments contained a grid (unelectrified) floor, while the goal box floor was made of wood. At the far end of the choice chamber was a centrally located window (8.0 cm square) which led to the goal box. Interchangeable partitions and/or platforms could be installed in the choice chamber to form three separate spatial problems. Problem A consisted of a diagonally oriented partition (39.0 cm long) which left a 4.5 cm space between the end of the partition and the wall of the apparatus on the right side (see Fig. 4, top panel). Problem B consisted of a downward sloping platform (30.5 cm long) which was raised 7.7 cm above the grid floor at its highest point (Fig. 4, middle panel). Problem C consisted of an upward sloping platform (60.0 cm long) which contained a hole (7.0 cm square) immediately in front of a partition (19.5x 11.0 cm). This partition was located 12.0 cm distant from the start box door (Fig. 4, bottom panel). The apparatus was covered by a transparent Plexiglas sheet and was illuminated by conventional ceiling fluoresent lights. Activity was measured in a 56.0x224.0 cm open field enclosed on three sides by the walls of the room and on the

GENERALIZED LEARNING DEFICIT

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TABLE 2 MEAN LEARNING (INITIAL AND TOTAL ERRORS) SCORES FOR ALL GROUPS ON THE THREE SPATIALPROBLEMS Problem A

Problem B

Problem C

Group

N

Initial

Total

Initial

Total

Initial

Total

C MR PRF LPA

10 5 6 6

3.6 7.6* 6.7* 2.7

6.4 35.4* 15.2" 5.0

2.3 8.6* 6.3* 1.7

5.4 46.6* 19.8" 5.2

2.8 5.0* 4.7* 1.2

4.7 20.2* 9.7* 1.5

*Differs from sham controls, Mann-Whitney U, p<0.05.

fourth side by a 32.5 cm high partition. The floor of the field was divided into sixteen 28.0 cm squares. Lighting was provided by conventional ceiling fluoresent lights.

Procedure Following a 3-week recovery period, the animals were deprived of water in their home cages for the duration of the learning experiment. On Day l, each animal was allowed to explore the apparatus (containing no partitions or platforms in the choice chamber). A dish of water as well as a dish of sweetened wet mash were available in the goal box from which the animal was permitted to ingest for l0 min. On Day 2, each animal was given l0 preliminary training trials. Each trial began by placing the animal in the start box and raising the start box door. In most instances, the animal would readily leave the start box, traverse the choice chamber, enter the goal box through the centrally located window, and ingest the water and/or mash. After l0 sec, the animal was transferred to the restraining cage to wait the next trial. Problem A was given on Day 3, Problem B on Day 4, and Problem C on Day 5. Ten trials were given on each problem with an intertrial interval of 90-300 sec. With respect to Problem A, an error consisted of traversing beyond the left end of the diagonally oriented partition by at least the length of the animal's body (excluding the tail). For Problem B, an error consisted of passing under the downward sloping platform by at least the length of the animal's body and an error on Problem C consisted of traversing beyond the centrally located hole in the upward sloping platform by at least the length of the animal's body. (See Fig. 4 for further details.) Both initial and total (initial combined with repetitive) errors were recorded on each trial. After completing training on Problem C, the animals were placed on ad lib food and water. Forty-eight hours later, each animal was placed in the center of the open field and allowed to explore during a 10-min period. The number of squares entered by all four paws was recorded. At the completion of the activity test, each brain-damaged animal was killed with an overdose of chloral hydrate and the brain removed, fixed, sectioned, and photographed in a manner described in Experiment 1. RESULTS

Learning Table 2 presents the mean performance scores for all groups on Problems A, B, and C. These results will be discussed in terms of the site of damage.

Group C. No control animal made more than 5 initial errors within 10 trials on each of the three problems. While Problem A tended to be the most difficult and Problem B the least difficult, none of the differences in performance scores approached statistical significance. Group MR. The lesion placements in this group were not remarkably different from those described in Experiment 1 for the corresponding group. It will be noted in Table 2 that these animals made significantly more errors than the controls in learning each of the three problems. Group PRF. All animals of this group had lesions similar to the one shown in Fig. 2. As in the case of Group MR, this group was significantly inferior to the controls in errors scores on each of the three problems. Group LPA. Except for being somewhat smaller, the lesions suffered by this group were comparable to the one shown in Fig. 3. As in Experiment 1, this group tended to be superior to the controls in error scores on each of the three problems, but none of the differences approached statistical significance. However, Group LPA was significantly superior to the controls when the measure of performance involved either pooled initial errors or pooled total errors committed on all three problems (ps<0.05).

Other Observations Body weight. At 42 days of age, the mean body weights oi Group MR (111 +7 g) and Group PRF (125_+6 g) were significantly (ps<0.05) less than that of Group C (147_+6 g). The difference between Group C and Group LPA (139_+8 g) was far from statistical significance. Activity. The number of squares traversed within a 10-rain period was significantly (p<0.05) less in Group LPA (44.2__+ 10 squares) and almost significantly (p =0.10) less in Group PRF (75.5-+12 squares) than in Group C (114.9-+12 squares). Although Group MR (145_+24 squares) was more active than the controls, the difference failed to reach statistical significance. General health and behavior. As in Experiment 1, the general appearance of the brain-damaged animals at the time of the learning tests was one of good health and alertness. During the first postoperative week, however, most of the animals of Groups MR and PRF displayed a defective labyrinthine reflex and four animals of Group LPA displayed hyerextension of the forelegs during locomotion. Three of the animals of the latter group exhibited a tremor at rest of the head.

114

T H O M P S O N , RAMSAY AND Y [ DISCUSSION

G E N E R A L DISCUSSION

These results leave little doubt that weanling rats with lesions of the MR or PRF show striking deficits on simple spatial tasks learned under the condition of an appetitive motive. The fact that Group LPA sustained larger brainstem lesions than Groups MR or PRF, and yet did not show any evidence of a learning disturbance on these tasks, indicates that lesion locus rather than lesion presence or lesion size is responsible for the production of the learning deficits observed in the latter two groups. Other studies, using adult rats, have likewise shown that MR or PRF lesions produce learning deficits on appetitive tasks. For example, it has been reported that MR rats are impaired in the performance of a radial maze [17], a light gray versus dark gray discrimination [18], and a successive visual discrimination [t]. Although MR animals have been reported to acquire a food-motivated white versus black discrimination as fast as controls [1,18], there is one study which showed that lesions of the MR or PRF produced relearning disturbances (indicative of an acquisition defect) on a water-motivated white versus black discrimination [15]. (Conceivably, only large MR lesions, such as the ones investigated in the latter study, will produce deficient acquisition of a white versus black discrimination.) Relearning disturbances on appetitively motivated latch-box tasks have also been observed in rats prepared with MR or PRF lesions I5,14]. The finding that lesions of the LPA in our weanling rats tended to facilitate learning of the spatial tasks (as well as the discrimination tasks studied in Experiment 1) was totally unexpected in light of the learning impairments observed in cats with similarly placed brainstem lesions [6]. It remains to be seen whether this discrepancy is due to the difference in the species investigated, the magnitude of the lesions, and/or the age of the subject at the time the lesions are produced.

Although involving the investigation of lesions in wean-. ling rats, the results of Experiments 1 and 2 can be viewed as providing further support for the hypothesis that the regions of the MR and PRF serve an important function in the e s t a b lishment of a wide range of laboratory tasks. Those animals suffering damage to these brainstem regions were found tt~ be severly deficient in learning a white-black discrimination. an I 1° incline plane discrimination, a 3-cul maze, and a series of simple spatial problems. Other tasks that have been found to be sensitive to selective lesions of the MR and PRF include latch-box habits [5,14] and T-maze reversals [111. The apparent participation of the MR and PRF in the acquisition of many different laboratory tasks raises the important question concerning the role played by these brainstem regions in the general learning process. According to one lesion analysis of a variety of learned habits [10,12], the brain of the rat can be divided into a number of "specific" cortical-subcortical (visual, proprioceptivekinesthetic, cognitive map, skilled movement, etc.) mechanisms and a seemingly diffuse "n o n sp eci f i c" subcortical mechanism. The normal performance of most learned responses appears to require the integrity of the nonspecific mechanism (of which the MR and PRF are a part) and one or more specific mechanisms, the latter depending on the perceptual, motor, and motivational demands of the task itself. In light of this analysis, learning can be conceived as the engagement of the appropriate specific mechanisms with the nonspecific mechanism. It is not unreasonable to assume that this engagement is accomplished, at least in part, by the activities of the nonspecific mechanism, possibly through the operation of attentional processes that occur within the framework of an ~'anticipatory set" [4. 9~ t3]. While this assumption requires further specification and linkage to data, some support comes from the finding that implicate the MR and PRF in attentional processes [2,16].

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10. Thompson, R. Functional organization of the rat brain. In: Neuropsychology after Lashley, edited by J. Orbach. Hillsdale: Erlbaum, 1982. 1I. Thompson, R. Abnormal learning and forgetting of individual spatial reversal problems in brain-damaged rat. Physiol Psychol It: 35-46, 1983 12. Thompson, R. Brain systems and long-term memory. Behav Neurol Biol 37: 1-45, 1983. 13. Thompson, R., K. Gallardo and J. Yu. Posterolateral hypothalamic and midbrain central gray lesions impair visual and spatial reversal learning: Further additions to the "'general learning system" of the rodent brain. Physiol Psychol 11: 93-102, 1983. 14. Thompson, R., C. E. Gates and S. A. Gross. Thalamic regions critical for retention of skilled movements in the rat. Physiol Psvchol 7: 7-21, 1979. 15. Tllompson, R. and P. H. Spiliotis. Subcortical lesions and retention of a brightness discrimination in the rat: Appetitive vs. aversive motivation. Physiol Psychol 9: 63-67, 1981. 16. Wirtshafter, D. and K. E. Asin. Evidence that electrolytic median raphe lesions increase locomotion but not exploration. Physiol Behav 28: 74%754, 1982. 17. Wirtshafter, D. and K. E. Asin. Impaired radial maze performance in rats with electrolytic median raphe lesions. Exp Neurol 79: 412-421, 1983. 18. Wirtshafter, D., K. E. Asin and E. W. Kent. An analysis of open field hyperactivity following electrolytic median raphe lesions in the rat. Soc Neurosci Abstr 6: 422, 1980.