BEHAVIORAL AND NEURAL BIOLOGY 27, 433-453 (1979)

Hyperactivity, Aphagia and Motor Disturbance following Lesions of Superior Colliculus and Underlying Tegmentum in Rats SIAN G. POPE 1 AND P A U L D E A N 2

Department of Psychology, University of Sheffield, Sheffield SIO 2TN, England To investigate possible nonvisual functions of the superior colliculus, hooded rats with extensive collicular lesions were tested for disturbances of activity, feeding, and motor performance. Their pattern of behavior in the open field was abnormal, with markedly increased locomotor activity accompanied by a decrease in rearing and defecation. Damage to the deep layers of the superior colliculus may have been involved in these effects. Feeding and motor disturbances were also observed, but these were probably caused, at least in part, by invasion of the dorsal tegmentum underlying the colliculns; the aphagia, which appeared to have a strong motor component, was much worse in animals with substantial tegmental damage. The superior colliculus in rats may be involved in the regulation of activity, exploration, and possibly fearful behavior. It is unclear why large lesions of the superior colliculus increase activity in rats, but apparently reduce it in other species.

Much of the recent work on the functions of the superior colliculus has been concerned with its role in visually guided behavior. In this context, the results of an experiment to measure visual acuity in rats after very large lesions of the superior colliculus were surprising: Acuity was unaffected, but informally observed changes in activity and feeding occurred that were not, it seemed, the result of any visual disturbance (Dean, 1978). The rats with lesions of the superior colliculus lost weight for several days after operation and thereafter required more food than normal animals to maintain body weight, apparently because they were clumsy at eating hard food pellets and dropped an excessive amount of dust on the floor of the cage. They also seemed more active than normal both in the testing box and when handled. These informal observations were surprising for another reason. In other species very large lesions centered on the superior colliculus have 1 M.R.C. research student. 2 We would like to thank Peter Redgrave for helpful discussions, and Nigel Foreman for sending us a preprint of Foreman, Goodale, and Milner (1978). 433 0163-1047/79/120433 -21 $02.00/0 Copyright © 1979by AcademicPress, Inc. All rightsof reproductionin any form reserved.

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not been reported to affect eating, and seem to reduce rather than increase activity. Tree shrews with such lesions "usually remained motionless in their home cage" (Casagrande, Harting, Hall, Diamond, & Martin 1972), although lesions restricted to the superficial collicular layers gave normal cage behavior. Monkeys with complete removal of the superior colliculi were also reported to spend their time, when not hungry or asleep, sitting and staring aimlessly into space (Denny-Brown, 1962). Similarly, Myers found cats were "somewhat hypoactive" after complete lesions of the superior colliculi and damage to the underlying tegmentum (Myers, 1964, p. 82). It was therefore important to confirm the original observations of hyperactivity and disturbance of eating in rats with large lesions of the superior colliculus. In the present experiment, collicular rats were tested in an open field, and their body weight and food and water requirements measured. Since the eating difficulties observed in Dean (1978) appeared to be caused by clumsiness, tests of motor performance were also given. It was hoped to relate any behavioral deficits found to damage to specific anatomical areas, since the lesions in Dean (1978) had extended outside the superior colliculus into surrounding structures, such as the central gray, pretectum, and dorsal tegmentum. In fact, four out of the eight rats given collicular lesions in the present experiment developed an unexpectedly severe aphagia after operation, and subsequent histological examination showed that only in these four was a particular area of the dorsal tegmentum damaged. Because of this finding, the animals were divided post hoc into two groups, namely group SC (the four rats with mild aphagia and less severe tegmental damage) and group SCT (the other four rats with pronounced aphagia and more extensive damage to the tegmentum).

METHODS

Subjects The subjects were 16 female hooded Lister rats, weighing about 250 g at the start of the experiment.

Housing The rats were kept individually in plastic cages with metal grid tops and sawdust on the floor. Apart from postoperative Days 41 and 42, food and water were available throughout the experiment. The food was Labsure Animal Diets CRM nuts, which were cylinders 1 cm in diameter and 1 to 2 cm long. The food hopper was a depression of the metal grid top into the cage, with bars about 6 mm apart. The water was kept in drinking bottles, each supplied with a 6-mm diameter tube, normally closed by a ballbearing. The rats were kept on a normal day-night cycle (dark 2000 to 0700 hr), and testing was always done in the day time.

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Preoperative Eating and Drinking For 10 days before operation the amounts of food and water consumed by each animal were estimated by daily weighing the contents of the food hopper and measuring the volume of water in the bottle. The rats were also weighed each day.

Surgery Eight of the rats were given bilateral, electrolytic lesions of the superior colliculus of similar size to those in Dean (1978). The animals were anesthetized with chloroform, then injected intraperitoneally with Sagatal (sodium pentobarbitone, 40 mg/kg). Penthrane (methoxyflurane) was used as a supplementary anesthetic if required during the operation. With the incisor bar 5 mm above the ear bars, the coordinates used were 4.8 mm behind bregma, 1.6 mm lateral to the midline, and 4.5 mm deep to the cortical surface. The lesions were made by direct current passed through an anode made from a 4-gauge stainless-steel insect pin, insulated except for a 1-mm tip. The current was increased from 0 to 4 mA over 10 sec, kept at 4 mA for a further 20 sec, then reduced to 0 over 5 sec. Four animals were given sham operations. For these the electrode was lowered 3 mm from the cortical surface in the same coordinates and no current was passed.

Postoperative Testing Eating and Drinking The amount of food taken from the hopper and water drunk by each animal, and its body weight, were recorded daily as before operation for 40 days after surgery. The supplementary food required by some animals is described in the Results section below. After 40 days the animals were food deprived for 24 hr; then the time taken for each to consume one 1.5-cm-long food pellet, placed in the food hopper, was measured. The rats were then given 15 g of food, and the test was repeated after a further 24 hr.

Open Field The operated animals were tested in the open field 10, 20, 30, and 40 days after surgery. The open field, based on Broadhurst's standardized apparatus (e.g., Broadhurst, 1960), had a circular base of white plastic, 81 cm in diameter, with aluminum walls 61 cm high. The floor was marked into equal areas by three concentric circles divided into segments by lines radiating from the center (see Broadhurst, 1960, Plate 1). Four 150-W bulbs in metal reflectors 100 cm from the floor gave an illumination of about 20 fc at floor level (measured with a United Detector Technology Model 40A Optometer). White noise was not provided.

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Over the 2-min test period the following were recorded: number of lines crossed, number of times the animal reared or groomed, and the number of fecal boli deposited.

Motor Performance The operated animals were given the following tests on Days 10, 20, 30, and 40 after operation. (a) Raised platform. This test was included after the collicular rats had been observed in the first few days after operation to walk or jump off the edges of tables. The animals were placed for 2 min on a 50 x 32 cm platform, 19 cm high, and the number of times they walked, fell, or jumped off was recorded. (b) Ladder and beam (adapted from Altman & Sudarshan, 1975). The animals were required to climb a 42-cm-long, 7-cm-wide wooden ladder inclined at 25° to the vertical and with rungs 2 cm apart, then traverse a 40-cm-long, 2.5-cm-wide beam at its top. (c) Grip (adapted from Altman & Sudarshan, 1975). The rat was suspended by the base of its tail so that its forepaws touched a stout horizontal wire 42 cm from the ground. Once the rat had gripped the wire it was released, and the length of time it supported itself was recorded. (d) Righting. The animal was put on its back in the experimenter's palm, and the time it took to right itself recorded.

Histology When testing had been completed, the animals with collicular lesions were given a lethal dose of Sagatal, then perfused through the heart first with heparinized saline, then with 10% buffered formal saline. The brains were embedded in low-viscosity nitrocellulose. Coronal sections of 40 t~m were taken in a plane as close as possible to that used by K6nig and Klippel'(1963), and every fourth section through the lesion was stained with cresyl violet. The borders of the lesions were then drawn onto brain outlines taken from the photographs in K6nig and Klippel's atlas. Representative drawings for individual animals are shown in Fig. 1. The animals have been divided into two groups (see the introduction section). The lesions of the animals with mild aphagia (group SC) are shown in Fig. la and those of the severely aphagic (group SCT) animals in Fig. lb. By superimposing tracings of the lesion outlines, one area was found which was damaged in all the SCT rats and none of the others. This area is shown in Fig. 2a. Also shown in the figure (and in Fig. 2b) is a tentative estimate of the location of the ventral boundary of the superior colliculus (cf. Tokunaga, 1970; Zeman & Innes, 1963). This estimate was drived from examination of layers IV to VII (terminology as in Kanaseki & Sprague, 1974) in fiber- and counterstained normal brains, and is tentative because in our material these layers generally lacked abrupt borders with

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surrounding ventral areas, but rather merged gradually into them. The area of lesion common to the SCT animals alone was probably outside the superior colliculus in the underlying dorsal tegmentum. This region of tegmentum is part of what is called variously the midbrain reticular formation or the area cuneiformis, and may include part of the nucleus of the posterior commissure. Superimposing tracings of lesion outlines also gave the area of damage common to all eight animals, shown in Fig. 2b. Despite clear individual variations in the amount of damage to hippocampus, pretectum andposterior thalamus, central gray, and the posterior portion of the superior colliculus, the area of lesion common to all animals was confined to the superficial and deep layers in the anterior part of the superior colliculus, to the lateral part of central gray, to immediately overlying cerebral cortex, and to the pretectum mainly on one side. The dorsal tegmentum was probably also damaged (level A1020 ~), but the indistinctness of the ventral collicular boundary makes it hard to be certain of this. RESULTS As stated in the introduction section the eight animals with lesions of the superior colliculus were divided into two groups, on the basis of the severity of their postoperative aphagia. Group SC (145, 148, 149, and 152) resumed feeding from the hopper 5 to 7 days after surgery. Group SCT (141, 143, 154, and 157) ate nothing from the hopper, at least until after Day 40 (143 died on Day 19; details for the others are given below). Results are therefore presented separately for these two groups.

General Observations Soon after surgery it became obvious from watching the animals in their home cage and during weighing that the collicular rats were abnormal in a number of ways. These are briefly listed below. Except for the first the abnormalities were in general more pronounced in the rats of group SCT, and severest of all in the two animals of that group (141 and 143) with the largest and deepest lesions. 1. Recovery from anesthesia. Apart from 141 and 143 the collicular rats were violently hyperactive for several hours after recovering from the anesthetic, frequently hurling themselves against the roof and walls of the cage. This extreme hyperactivity disappeared by the day after operation. 2. Posture and gait. For the first few postoperative days the animals were often seen stretched upward on their hindlegs with their snouts pushed into a back corner of the cage. Their walking seemed curiously mechanical, partly because they never stopped to sniff or look around, but kept moving with their heads held stiffly extended in front of them. They also tended to walk with their bodies held high off the ground, apparently because the hindlegs in particular were more extended than normal.

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3. Grooming. A tremor of the front paws, in which they were rapidly crossed and uncrossed in a scissoring movement, interfered with grooming the face. This tremor did not appear unless the animals were grooming, eating, or drinking, and so resembled an intention tremor. Grooming was also often inaccurate, in that the grooming movement was carried out a few millimeters above the body surface. In addition, t h e animals had particular difficulty in grooming the more caudal parts of the body, since they tended to lose their balance when trying to reach them. 4. Reactivity. In many ways the animals were less easy to disturb than normal rats. They sometimes continued sleeping while their cage was m o v e d or they themselves were picked up. They did not react to the presence of people, neither freezing nor trying to avoid or investigate them. For the first few days after operation they also appeared unaware of other features of the environment, such as walls and edges: They walked

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straight up to walls, not slowing down until they actually touched them, and walked off the edges of tables. In addition, 141 and 143 (the only animals tested) took no notice of other rats, but simply climbed over them if they were in the way. When some reaction to a disturbance did occur, it was often of a different pattern from that observed in the control rats. For example, if disturbed in their home cage, the collicular rats would walk vigorously around in a stereotyped manner, rather than rear up on their hindlegs to investigate the source as the control rats did. The collicular animals often started violently when picked up, or touched from behind. T h e y were difficult to handle, becoming tense and struggling vigorously to escape. H o w e v e r , they did not attempt to bite, nor did they show signs of fear such as defecation, urination, or vocalization. In fact, such signs were not observed in any situation. They quickly left the cage when its top was removed, whether or not there was a surface for them to jump down to, and immediately fell or j u m p e d off when placed on the experimenter's arm. 5. Activity. It was difficult to say whether the collicular rats had a higher mean activity level than normal animals in their home cage. T h e y were

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clearly more active than normal, however, when removed from the home cage. They started to walk as soon as they were placed on a fiat surface, and continued walking in the rather mechanical fashion described above, without pausing to rest, groom, or look around for as long as they were observed. 6. Other symptoms. All the animals were exophthalmic, and 141, 143, and 157 had dilated pupils. All the animals in group SCT felt warmer than usual when they were picked up, although their rectal temperatures were normal. In general, these abnormalities were most marked the day after operation, and gradually decreased in severity over the next 5 to 10 days for group SC, and over about 20 to 30 days for group SCT. In both groups some persisted in attenuated form, for as long as the animals remained alive (45 days): paw tremor when grooming (and eating, see below), difficulty of waking and handling, lack of reaction to people, immediate walking when put on a fiat surface, and absence of investigatory head movements. Group SCT, in addition, remained exophthalmic, carried their heads stiffly extended, and walked with their bodies high off the ground.

Eating and Drinking Pre- and postoperative body weights for the four groups are shown in Fig. 3a, and the amounts removed from the food hopper, and drunk from the bottle, are shown for the normal animals, sham operates, and group SC in Figs. 3b and c. The short-term effects of the sham operation were mild. The rats in this group started drinking (more than 5 ml) on either the first or second day a) I"- -I-20" I IJJ

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after operation, and resumed eating at about the same time. The maximum weight loss for the group was 17.3 g (range, 14 to 26 g). Three longer term effects were observed. The animals drank 27% more than the unoperated animals over Days 6 to 20 (shams, 19.4 ml/day; unoperated animals, 23.1 ml/day; nt = n~ = 4, U = 0, p = .028 M a n n - W h i t n e y U test: Unless otherwise stated two-tailed p values are given throughout), perhaps to compensate for body fluid lost during surgery (Blatt & Lyon, 1968, p. 583). They also took 23% more food from the hopper Days 21-40, though this effect was not quite significant (shams, 22.9 g/day; unoperated animals, 18.6 g/day; U = 1, p = .058). Surprisingly, their weights on Day

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40 (relative to their weights on the day of surgery) were lower than those of the unoperated rats (shams, - 1.5 g; unoperated controls, + 16.0 g; U = 0, p = .028). It is possible that the extra food removed by the sham operates from the hopper was not eaten, but dropped as dust on the floor through clumsiness, since it neither led to increased body weight nor was accompanied by increased drinking. Some support for this interpretation comes from the times taken by the animals with sham operations to eat food pellets, which were 58% longer than the times taken by the unoperated animals (mean time for shams, 533 sec; for unoperated animals, 337 sec; U = 0, p = .028). However, the sham operates did not appear obviously clumsy, either when eating food pellets or in general. The animals in group SC were worse affected by the surgery than the rats given sham operations. They resumed drinking on Days 3 to 5, and eating from the hopper on Days 5 to 7. (The animal that failed to eat on Day 6, No. 148, was given 5 ml of chocolate Complan (Farley Health Products) by hand on that day.) The maximum weight loss for the group was 46.3 g (range, 38-52 g). On all these measures there was no overlap between group SC and the sham operates (U = 0,p = .028). Interestingly, the SC rats were observed trying to eat and drink before they succeeded. Initially, they were unable either to grasp the drinking tube with their forepaws, or to lick the end of the tube. Their attempts to grasp the tube were accompanied by a rapid tremor of the forepaws (see above), which also hampered their efforts to hold small pieces of food, detached from the pellets in the hopper, while they chewed them. The animals in group SC took more food from the hopper than the normal animals after Day 10. This may have occurred in part to compensate for the initial postoperative weight loss, but they continued to take more food after Day 20 when their weights had very nearly caught up with those of the unoperated rats. (Mean food taken from hopper, Days 21-40, 25.4 g/day; unoperated animals 18.6 g/day; U = 0, p = .028). They also took more than the animals with sham operations over this period, but the difference was not significant (U = 4, p = .34). Since, as with the sham operates, the increased food removed from the hopper was not accompanied either by increased drinking or abnormal body weight, it is possible that these animals too dropped food onto the cage floor as dust through clumsiness. Group SC rats were clearly clumsier at eating a single pellet from the hopper than either the shams or the unoperated rats, taking over twice as long as the normal animals (mean time taken, 731 sec; versus either shams or unoperated rats U = 0, p = .028). This was not because they were slower to notice that a pellet had been dropped into the hopper: All animals started trying to eat at about the same time. Unlike the sham-operated rats, they seemed to have difficulty biting off pieces of the pellet, which often bounced out of their incisors when they tried to grip it

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in the hopper: Frequently, they had to enlist their forepaws to try and hold the pellet still while they bit a piece off it. They also tended to drop fragments of food from their forepaws, and had to spend time looking for them. The eating and drinking of the rats in group SCT was so disturbed by the operation that if left with pellets in the hopper as the only source of food they would almost certainly have died. When none of them had eaten in the first 5 days after surgery, they were hand-fed chocolate Complan from a syringe daily until Day 20. This was supplemented from Day 11 onward with a large bowl of palatable mash put in the home cage. Pellets and a bowl of water were also available in the home cage after Day 20. The mash was discontinued as soon as an animal showed signs of being able to eat pellets. Even with this treatment the animals in group SCT lost an average of 85 g after operation (about 30% of their preoperative body weight), and 143 died on Day 19 despite intragastric tube feeding for the previous 4 days. The hand feeding was not successful at first: The rats struggled violently when held, did not lick the nozzle of the syringe, and appeared even to have difficulty swallowing liquid when it was placed in their mouths, instead making curious rotatory movements of the jaws. Their behavior for the first few days when a bowl of mash was placed in the cage was also unusual. They seemed to become very excited, running rapidly around the cage and through the food dish, scattering the contents and getting their fur covered with mash. They often stopped with their front paws in the mash, but then made such violent "scissoring" movements with them that food was further splashed into the cage. They also tended to make ineffectual digging movements in and around the food, filling the dish with sawdust. The only mash that actually got consumed by these animals at this stage was either licked off the forepaws, or other parts of the body during grooming. However, since their grooming was inefficient, much of their fur remained matted with dried food. Fortunately, the skills of the animals improved so that within a few days they were able to eat enough to put on weight, either by transferring the mash from the bowl to their mouths with their forepaws, or licking it up directly from the bowl. The three surviving animals of this group were also very clumsy in their first attempts to eat food pellets, 20 to 25 days after operation. They seemed unable to pick a pellet up and bite pieces off it as normal animals do, but instead tried to hold it on the cage floor and gnaw it there. Long periods were spent in these attempts, often with no apparent success. Later, the tremor in the front paws of 154 and 157 diminished enough for them to pick the pellets up, but they still lost food by letting it drop out of their mouths, or by dropping the piece held in their paws when it got small. The floors of their cages became littered with rounded fragments of

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pellets. By Day 40, animals 154 and 157 could maintain body weight on pellets alone (in the cage), but 141 could not. On Days 41 to 43, the pellets and water in the cage were removed, leaving only the water in the bottle and the pellets in the hopper. All three animals lost weight in these circumstances, although all drank some water, and 154 and 157 removed from the hopper about 80% of the food taken by normal animals. Even at this stage, however, 141 ate no food from the hopper at all.

Motor Performance All the rats with collicular lesions were transiently impaired on some of the tests of motor performance, with the impairments tending to be severer and longer lasting in group SCT. No animal with a sham operation fell or j u m p e d off the raised platform on any testing day. On Day 10 after operation the group SC animals fell or j u m p e d off a mean of 1.5 times (ranges, 1-2) and the SCT group 10 times (2-14). Both the collicular groups were thus impaired relative to the sham operates (U = 0, p = .028): The difference between the collicular groups was significant only with a one-tailed test (U = 1, p = .029). Two animals in group SCT and one in group SC fell off twice on Day 20; thereafter all stayed up during the test periods. All the collicular animals except 148 gripped the horizontal wire for less long than the sham o p e r a t e s - - t h e r e was no overlap between the times of the shams and the other collicular rats on any testing day. Group SCT did worse than group SC on Day 10 (SCT mean time 1.3 sec; SC 4.8 sec; U = 0, p = .028), but the difference disappeared on subsequent tests. This weakness in grip seemed to cause both groups difficulty in climbing the ladder in the ladder and beam test on Day 10, but whereas the group SC animals eventually reached the top, SCT rats did not. Neither group successfully traversed the beam. The impairments on the ladder and beam disappeared by Day 20 for group SC, and by Day 30 for group SCT. Finally, on Day 10 alone the righting reflex was delayed for the four rats in group SCT (mean, 17 sec) and for 149 (4 sec) and 152 (2 sec) in group SC. The other animals righted immediately.

Open Field Group scores for locomotor activity, rearing, and defecation are shown in Fig. 4. These have been averaged over the 4 days of testing (10, 20, 30, and 40 days after surgery). N o data from 143, who died on Day 19, has been included, so the group SCT scores are for three animals only. Both collicular groups had locomotor activity scores about 2.5 times greater than those of the sham-operated animals. There was no overlap between any collicular and any sham score (na = 7, n2 = 4, U = 0, p = .006). The scores for the two collicular groups were very similar (nl = 3, n2 = 4, U = 5, p = .86). It seemed from observation that the animals with

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superior colliculus lesions achieved their high activity scores both by running for more of the time than the sham-operated rats, and by running faster. In fact, the collicular rats spent so much time running they had little time for other activities. It also seemed that they spent more of the test period in the outer parts of the field near the walls, but this was not formally recorded. Both collicular groups reared less than the animals with sham operations (nl = 7, n2 = 4, U = 0, p = .006), and group SC reared less than group SCT (though with only three animals in group SCT, this difference could not quite reach significance with a two-tailed test; n, = 4, n2 = 3, U = 0, p = .056). The pattern of rearing in the SCT rats was slightly different from that o b s e r v e d in the sham operates: The SCT animals tended to rear two or three times in quick succession without moving from the same spot, whereas the sham operates tended to rear once between periods of running. The n u m b e r of fecal boli deposited was significantly less for either collicular group than for the shams (n, = 7, n2 = 4, U = 0 , p = .006): Only one animal (149) with a lesion of the superior colliculus ever defecated during the tests. F o r the final measure, amount of grooming (not shown in Fig. 4), there were no significant differences b e t w e e n the g r o u p s - - n o n e of the animals g r o o m e d very often in the open field. The behavior of the animals with lesions of the superior colliculus changed little o v e r the 4 days of open field testing. In particular, their

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locomotor activity scores stayed the same, although on Day 10 their body weights were low and the SCT rats in particular were presumably hungry. Both locomotor activity and rearing declined slightly with testing in the sham-operated animals, but the greatest change was in defecation: 64% of their total defecation occurred on the first day.

DISCUSSION

Open-Field Behavior All eight animals with large lesions of the superior colliculus ran more, reared less, and defecated less in the open field than sham-operated controls. The effects on locomotor activity in particular were large: On average, a 2.5-fold increase. Further experiments have shown that these pronounced effects are not produced by damage confined to overlying cortex and hippocampus (Dean & Key, in preparation), and are long lasting--16 months after surgery the mean activity score for nine male rats with superior colliculus lesions was 2.6 times greater than the score for a control group (Pope & Dean, in preparation). This last result shows that the effects of the lesions on open field behavior are not the result of short-term postoperative changes in, for example, hunger or amount of food eaten. Additional evidence for the reliability of these changes in open-field behavior after collicular damage comes from a report by Foreman, Goodale, and Milner (1978), published while this manuscript was in preparation. Foreman et al. (1978) also found that rats with large lesions of the superior colliculus were over twice as active as sham operates, and that they reared significantly less. In addition, the most active collicular rats defecated less than the control animals (Goodale, personal communication). Previous work on lesions of the superior colliculus and open-field activity in rats has not produced altogether clear results. Altman (1962) found about a 2.5-fold increase in locomotor activity after deep lesions of the superior colliculus, but since part of the test arena was dark and part light this increase was confounded with a possible decrease in light aversion, and in fact Altman himself attributed the activity change after collicular lesions to this factor. Other experiments have found either no change in open-field activity after damage to the superior colliculus (Goodale & Lister, 1974) or only a slight (though significant) increase (34%) (Smith & Weldon, 1976). Apparently, the lesions in Goodale and Lister's study were restricted to the superficial layers of the superior colliculus (Foreman et al., 1978), suggesting that it may be necessary to invade the deep layers to produce an increase in locomotor activity. The small effect of collicular lesions on activity found by Smith and Weldon (1976) might also be explained by this factor, since at least in the case of their smallest lesion (Fig. 2, p. 383) very little damage was done to the deep collicular layers. However, the effects of more selective lesions need

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to be studied before precise conclusions can be drawn about the role of different structures in open-field behavior, and these are currently under investigation. Normal rats deprived of food, or tested at their circadian activity peak, show increases in both walking and rearing over baseline rates (Prescott, 1970). The fact that large lesions of the superior colliculus increase walking but decrease rearing suggests that their effects cannot be simply interpreted as an increase in "general activity." Rearing in the open field is probably in part an exploratory response (e.g., Miezejeski & Hamilton, 1977; Prescott, 1970), and there is other evidence that lesions of the superior colliculus reduce exploration. Foreman et al. (1978) recorded head raising and sniffing in the open field and found that they were also reduced in frequency after superior coUiculus ablation. Marshall (1978) tested collicular rats in an open field containing objects, and found that the animals reared less than controls, rarely turned their heads to investigate objects which contacted the vibrissae, and even when objects were in their path they "seemed to steer themselves around objects before they got near them by aligning their body axes before they approached objects" (Marshall, 1978, p. 210). Similar behavior has been observed when obstacles were unexpectedly placed in the paths of collicular rats running for food (Dean & Singleton, unpublished results; Pope & Dean, in preparation). An additional effect of the superior colliculus lesions on open-field behavior in this experiment was to reduce the amount of defecation. A similar reduction was observed in a subsequent experiment using an elevated maze (Dean & Key, in preparation) with collicular and control rats both at 80% body weight, suggesting that the differences in defecation observed in the present experiment were not wholly the result of postoperative changes in food intake. It is possible, rather, that the collicular rats were less fearful than normal, as other aspects of their behavior indicate. One is their lack of reaction to an experimenter's presence, approach, or other movement (cf. Goodale & Murison, 1975, p. 253). Even when actually grasped or moved from one place to another, the collicular rats in the present experiment still failed to show signs of emotional disturbance other than startle and struggling in the experimenter's hand: There was no freezing, vocalization, or emotional elimination. Another possible sign of reduced fearfulness in the rats with superior colliculus lesions was their tendency to jump down from surfaces when normal animals did not (see also Barnes, Smith, & Latto, 1970, p. 242). Again, smaller lesions are needed to determine how far these effects were produced by damage to structures outside the superior colliculus, in particular the mesencephalic central gray matter. Finally, the increase in locomotor activity shown by rats with large lesions of the superior colliculus contrasts sharply with the apparent

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hypoactivity found after similar lesions in other species (see the introduction section). It is not clear whether the difference reflects only that the rats were tested in an open field while the other animals seem to have been observed mainly in their home cages, or whether it reveals a fundamental difference in collicular function in different species. To summarize, all eight rats with large lesions of the superior colliculus ran more, reared less, and defecated less in the open field than control rats with sham operations. These changes suggest that such lesions reduce exploration and fearfulness, while increasing locomotor activity. It is possible that damage to deep layers of the superior colliculus is particularly important in producing some of these effects.

Aphagia and Motor Disturbances The four animals with collicular lesions that showed prolonged disturbances of feeding had damage to a particular area of the dorsal tegmentum, ventral to the superior colliculus (Fig. 2a). It seems likely that this tegmental damage was instrumental in producing the aphagia. First, only this region was destroyed in all four severely aphagic animals and in none of the others. Secondly, previous reports have shown that lesions in this area or close to it produce aphagia (e.g., Blatt & Lyon, 1968; Gold, 1967; Parker & Feldman, 1967) with symptoms very similar to those described here (e.g., Lyon, Halpern, & Mintz, 1968, p. 330). It is unclear whether destruction of the superior colliculus alone causes feeding difficulties. Certainly many of the lesions in the papers referred to above encroached on the superior colliculus, and even the less impaired rats in the present experiment nonetheless had clear short- and long-term feeding problems. The fact that feeding difficulties after superior colliculus lesions have rarely been mentioned in the literature (though see Barnes et al., 1970) may not be important: If food were provided loose inside the home cage the postoperative aphagic period might be much reduced, and casual observation might not reveal the subsequent clumsiness. Also, substantial damage to deep collicular layers may be necessary to produce the deficit. On the other hand, Marshall (1978) specifically looked for feeding impairments after large lesions of the superior colliculus and failed to find any, while the performance of the rats with sham operations in the present experiment suggest that slow pelleteating may, in part, be a nonspecific effect of surgical interference or cortical damage. A further problem is the indistinctness of the boundary between the deep layers of the superior colliculus and the underlying tegmentum (cf. section on Histology), which makes it hard to say whether a given lesion is confined to either region. At present, there is no firm evidence for rejecting the conclusion that lesions centered on the superior colliculus only produce specific disturbances in feeding if they encroach on the underlying tegmentum.

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Despite the striking nature of the feeding disturbance produced by dorsal tegmental lesions, little is known about it. The boundaries of the critical area are not well defined (cf. Blatt & Lyon, 1968; Gold, 1967; Lyon et al., 1968; Parker & Feldman, 1967). This part of the dorsal tegmentum (midbrain reticular formation, area cuneiformis) is anatomically complex (see for example, the discussions in Donaldson, Dolphin, Jenner, Pycock, & Marsden, 1978; Lyon et al., 1968); which of the constituent structures are involved in feeding has not been determined. One important unanswered question is whether lesions in this area exert their effects on feeding through destruction of cell bodies or fibers of passage, or both. Another area of doubt is whether the impairment of feeding produced by these lesions is primarily motivational or the result of motor disturbance (cf. Lyon et al., 1968; Parker & Feldman, 1967). Certainly, the evidence of the present experiment suggests a strong sensorimotor component to the feeding difficulties. At various stages in the recovery of the SCT animals they seemed to be trying to eat but failing because of motor deficiencies. This was particularly true of their early encounters with hard food pellets. Even at the end of the experiment they were clearly poorly coordinated and clumsy at eating pellets, and one was unable to eat at all from the food hopper. Moreover, the animals were impaired on tests of motor performance, more so than the four animals in group SC with mild aphagia, and more severely early after operation when the feeding difficulties were more severe. The motor deficits may be due, in part at least, to inadequate sensory feedback, since the SCT animals seemed not to notice edges (early after operation) or whether their paws were immersed in liquid food. However, these observations do not establish whether the lesions have some effect on motivation in addition to causing motor impairments. In summary, the severe feeding difficulties observed in four of the animals with lesions of the superior colliculus were probably caused by damage to a part of the dorsal tegmentum (mesencephalic reticular formation, area cuneiformis). Whether superior colliculus destruction by itself has any effects on feeding is unclear. The effects of tegmental lesions on feeding seemed to be mediated at least in part by disturbance of motor function.

Other Effects As mentioned in the Results section, the animals with collicular lesions were abnormal in other aspects besides hyperactivity and impaired feeding. They were difficult to handle, in contrast to their hyporeactivity in other situations. Their behavior suggested that restraint was uncomfortable, rather than an occasion for fear or anger. They were difficult to wake. Their grooming was inefficient. All these peculiarities have been noted before in rats with lesions in the area of the boundary between superior

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colliculus, dorsal tegmentum, and central gray (e.g., Capps & Stockwell, 1968; Goodman, Jansen, & Dewsbury, 1971; Kesner, Fiedler, & Thomas, 1967; Liebman, Mayer, & Liebeskind, 1970; see also Swenson & Randall, 1977, for effects of large collicular lesions on grooming cats). Once again, the precise anatomical bases of these effects are unknown, in particular, whether they could be produced by lesions restricted to the superior colliculus. Finally, a very striking feature of the behavior of six of the animals was their violent hyperactivity when they first recovered from anesthesia (cf. Capps & Stockwell, 1968). This effect appears when large collicular lesions are made with anodal direct current, but not if they are made with radio frequency current (Foreman, personal communication) and so may be caused by metallic ions irritating tissue around the lesion site (cf. Rolls, 1970). The hyperactivity resembles the "explosive motor behavior" seen in similar circumstances after lesions of central gray (Blair, Liran, Cytryniak, Shizgal, & Amit, 1978), and this may be the structure which, when irritated, produces the effect. REFERENCES Altman, J. (1962). Effects of lesions in central nervous visual structures in light aversion of rats. American Journal of Physiology, 202, 1208-1210. Altman, J., & Sudarshan, K. (1975). Postnatal development of locomotion in the laboratory rat. Animal Behaviour, 23, 8%-920. Barnes, P. J., Smith, L. M., & Latto, R. M. (1970). Orientation to visual stimuli and the superior coUiculus in the rat. Quarterly Journal of Experimental Psychology, 22, 239247. Blair, R., Liran, J., Cytryniak, H., Shizgal, P., & Amit, Z. (1978). Explosive motor behaviour, rigidity and periaqueductal gray lesions. Neuropharmacology, 17,205-209. Blatt, B., & Lyon, M. (1968). The interrelationship of forebraln and midbraln structures involved in feeding behaviour. Acta Neurologica Scandinavica, 44, 576-595. Broadhurst, P. L. (1960). Applications of biometrical genetics to the inheritance of behaviour. In H. J. Eysenck (Ed.), Experiments in Personality, Vol. 1, pp. 3-102. London: Routledge & Kegan Paul. Capps, M. J., & Stockwell, C. W. (1968). Lesions in the midbrain reticular formation and the startle response in rats. Physiology and Behaviour, 3, 661-665. Casagrande, V. A., Harting, J. K., Hall, W. C., Diamond, I. T., & Martin, G. F. (1972). Superior colliculus of the tree shrew: A structural and functional subdivision into superficial and deep layers. Science, 177, 444-447. Dean, P. (1978). Visual acuity in hooded rats: Effects of superior collicular or posterior neocortical lesions. Brain Research, 156, 17-31. Denny-Brown, D. (1962). The midbrain and motor integration. Proceedings of the Royal Society of Medicine, 55, 527-538. Donaldson, I. M., Dolphin, A. C., Jenner, P., Pycock, C., & Marsden, C. D. (1978). Rotational behaviour produced in rats by unilateral electrolytic lesions of the ascending nor-adrenergic bundles. Brain Research, 138, 487-509. Foreman, N., Goodale, M. A., & Milner, A. D. (1978), The nature of postoperative "hyperactivity" following lesions of the superior colliculus in the rat. Physiology and Behaviour, 21, 157-160.

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Gold, R. M. (1967). Aphagia and~ adipsia following unilateral and bilaterally asymmetrical lesions in rats. Physiology and Behaviour, 2, 211-220. Goodale, M. A., & Lister, T. M. (1974). Attention to novel stimuli in rats with lesions of the superior colliculus. Brain Research, 66, 361-362. Goodale, M. A., & Murison, C. C. (•975). The effects of lesions of the superior colliculus on locomotor orientation and orienting reflex in the rat. Brain Research, 88, 243-261. Goodman, E. D., Jansen, P. E., & Dewsbury, D. A. (1971). Midbrain reticular formation lesions: Habituation to stimulation and copulatory behaviour in male rats. Physiology and Behaviour, 6, 151-156. Kanaseki, T., & Sprague, J. M. (•974). Anatomical organization of pretectal nuclei and tectal laminae in the cat. Journal of Comparative Neurology, 158, 3•9-337. Kesner, R. P., Fiedler, P., & Thomas, C. T. (1967). Function of the midbrain reticular formation in regulating level of activity and learning in rats. Journal of Comparative and Physiological Psychology, 63, 452-457. Krnig, J. F. R., and Klippel, R. A. (1963). The Rat Brain: A Stereotaxic Atlas of the Forebrain and Lower Parts of the Brain Stem. Baltimore, Md.: Williams & Wilkins. Liebman, J. M,, Mayer, D. J., & Liebeskind, J. C. (1970). Mesencephalic central gray lesions and fear-motivated behaviour in rats. Brain Research, 23, 353-370. Lyon, M., Halpern, M., & Mintz, E. (1968). The significance of the mesencephalon for co-ordinated feeding behaviour. Acta Neurologica Scandinavica, 44, 323-346. Marshall, J. F. (1978). Comparison of the sensorimotor dysfunctions produced by damage to lateral hypothalamus or superior colliculus in the rat. Experimental Neurology, 58, 203-217. Miezejeski, C. M., & Hamilton, L. W. (1977). Brain-lesion-induced hyperexploration. Bulletin of the Psychonomic Society, 10, 343-346. Myers, R. (1964). Visual deficits after lesions of brain-stern tegmentum in cats. Archives of Neurology, 11, 73-90. Parker, S. W., & Feldman, S. M. (1967). Effect of mesencephalic lesions on feeding behaviour in rats. Experimental Neurology, 17, 313-326. Prescott, R. G. W. (1970). Some behavioural effects of variables which influence the 'general level of activity' of rats. Animal Behaviour, 18, 791-796. Rolls, B. J. (1970). Drinking by rats after irritative lesions in the hypothalamus. Physiology and Behaviour, 5, 1385-1393. Smith, C. J., & Weldon, D. A. (1976). Hyperactivity and deficits in problem solving following superior colliculus lesions in the rat. Physiology andBehaviour, 16, 381-385. Swenson, R. M., & Randall, W. (1977). Grooming behaviour in cats with pontile lesions and cats with tectal lesions. Journal of Comparative and Physiological Psychology, 91, 313-326. Tokunaga, A. (1970). Neuronal structure of the superior colliculus of the rat. Journal of the Chiba Medical Society, 46, 289-299. Zeman, W., & Innes, J. R. I. (1963). Craigie's Neuroanatomy of the Rat. New York: Academic Press.