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Somatosensorimotor function of the superior colliculus, somatosensory cortex, and lateral hypothalamus in the rat
EXPERIMENTAL
NEUROLOGY
95,66 I-678 (I 987)
Somatosensorimotor Function of the Superior Colliculus, Somatosensory Cortex, and Lateral Hypothalamus in the Rat T. M. BARTH AND T. SCHALLERT’ Department of Psychology and Institute for Neurological Science, University of Texas, Austin, Texas 78712 Received June 13, 1986; revision received September IS, I986 The role of the superior colliculus in multimodal sensory function is unsettled, in large part because a clear distinction between the somatosensory effects and the postural/motor effects of damage to the deep layers of the superior colliculus has not been obtained. Unilateral lesions of the entire superior colliculus impair orienting of the head and eyes to tactile, visual, and auditory stimuli presented on the side of the body contralateral to the lesion; however, even in the absence of sensory stimulation animals with such a lesion tend to circle ipsiversively and fail to make contralateral head movements. To determine whether or not unilateral damage to the superior colliculus produces a somatosensory asymmetry independently of head movement/ circling biases, a neurological test was used in which lateral head or trunk movements were not required. Small pieces of adhesive-backed paper were attached to each forelimb and the latencies to contact and remove the stimuli were recorded. A battery of standard neurological tests was administered as well. The entire superior colliculus was removed unilaterally, and for comparison, the sensorimotor cortex or lateral hypothalamus were damaged in additional groups. Lesions of the superior colliculus produced the expected deficit in contralateral orienting and ipsilateral circling/pastural biases, but failed to produce a somatosensory asymmetry in the head movementindependent sensorimotor test. In contrast, both sensorimotor cortex and lateral hypothalamus lesions produced a severe asymmetry in the head-movement-independent sensorimotor test. We conclude that the superior colhculus is involved in the control of lateral head movements and that its role in somatosensory function is fundamentally different from that of the sensorimotor cortex or lateral hypothalamus regions. 0 1987 Academic Press. Inc.
Abbreviations: LH--lateral hypothalamus, 6-OHDA-6-hydroxydopamine, SC-superior colliculus, SMC-sensorimotor cortex. ’ This work was supported by funds from National Institutes of Health grants NS 17274 and NS23964 to T.S. We thank Theresa Dea Hemandez, Gary Knight, Don Goemer, and David Heard. Please address correspondence to Dr. Timothy Schallert.
0014-4886187 $3.00 Copyright 0 1987 by Academic Press, Inc. All rights of reproduction in any form reserved.
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INTRODUCTION The superior colliculus (SC), particularly the deep layers, are thought to be involved in multimodal sensory function (6,33). After unilateral ablation of the SC, rats and cats do not orient the head or eyes toward visual, auditory, olfactory, or tactile stimuli presented on the side of the body contralateral to the lesion and show normal or exaggerated orienting responses to stimuli in the ipsilateral sensory field or near midline (10, 11, 14, 3 1, 32). Some investigators have suggested that the orienting deficit may be directly related to a movement/postural asymmetry, rather than to a sensory dysfunction or to an impairment in sensorimotor integration (4, 14). Even in the absence of sensory stimulation, animals with unilateral SC lesions tend to circle toward the side of the damage and fail to make spontaneous contralateral head scans (4, 14,32). It remains unclear whether or not these animals possess the ability to detect and localize contralateral tactile stimuli. In recent work a behavioral task was developed to measure sensorimotor asymmetries independently of postural and head movement asymmetries in rats with unilateral lesions of the nigrostriatal system (27, 28) or neocortex ( 1,26). In this task, lateral head or trunk movements are not required. This is important because animals with 6-hydroxydopamine (6-OHDA)-induced depletion of striatal dopamine fail to make lateral head movements toward stimuli, such as a von Frey hair, applied to the contralateral side of the body [a deficit known as neglect or inattention (13, 15, 17, 18)]. Small pieces of adhesive paper are placed on the radial aspects of the wrists of each forelimb (bilaterally and simultaneously). The rat lifts each forelimb to the mouth to remove the adhesive patches, one at a time. Prior to surgery, rats may show a left, right, or no bias. After unilateral 6-OHDA-induced depletion of striatal dopaminergic neurons, rats always remove the ipsilateral adhesive patch first, followed by the contralateral adhesive patch [an ipsilateral sensorimotor bias (1, 5, 20, 27)]. The contralateral stimulus is rarely neglected, which is consistent with the view that in addition to asymmetrical sensory reactivity, motor dysfunction (particularly a deficit in the initiation of contralateral head movements) may contribute to the contralateral neglect observed in standard orientation tests. Motor and sensorimotor asymmetries can be dissociated by comparing the effects of electrolytic lesion-induced ablation of the substantia nigra vs unilateral infusions of 6-OHDA into the nigrostriatal system at a level anterior to the substantia nigra. Animals with 6-OHDA lesions show ipsiversive circling and postural asymmetry and fail to make contraversive lateral head turns, whereas animals with electrolytic lesions in substantia nigra show spontaneous contruversive circling and postural asymmetry and fail to make ipsiversive lateral head turns [(27) for review]. However, in the bilateral-stimulation test, after both types of lesion, the animals respond to the ipszlateral
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stimulus first on all trials. Presumably, this ipsilateral sensorimotor bias, which was detectable only by means of the bilateral-stimulation test, stemmed from common damage to the ascending dopaminergic nigrostriatal system in both groups, whereas the contraversive motor bias observed in rats sustaining electrolytic lesions of the substantia nigra was due to additional damage to caudal projections from the substantia nigra or to other nondopaminergic neurons (28). In the present study, the bilateral-stimulation test was used to determine whether or not rats with unilateral SC lesions have a sensorimotor asymmetry independent of the well known head movement/circling bias. For comparison, two previously untested groups were examined, including animals with unilateral electrolytic damage to the lateral hypothalamic region (LH; in the vicinity of ascending nigrostriatal neurons) and animals with damage to the sensorimotor cortex (SMC; aimed at the forelimb area). METHODS Animals Thirty-eight male Long Evans hooded rats, 3 to 6 months old and weighing 300 to 500 g, were randomly selected from our laboratory breeding colony. All rats were gently handled 10 min/day (or longer when necessary to establish obvious tameness) for 2 weeks before preoperative behavioral testing. The animals were maintained on a 12-h light: 12 h dark cycle with food and water freely available. Testing took place during the light portion of the cycle. Five animals were housed in individual Plexiglas cages and the remaining 27 were maintained in individual wire-mesh cages. Surgery All lesions were unilateral. The choice of hemisphere (left or right) was based on preoperative performance in the patch removal test (detailed below). For example, if the stimulus on the left limb was removed first on more than 50% of the trials, the lesions were placed in the right hemisphere, so that any lesion-induced change would be detectable beyond the endogenous asymmetry. Superior Colliculus. Ten animals were anesthetized with Equithesin (0.3 ml/100 g) and received three overlapping lesions in the superior colliculus in one hemisphere. In seven animals, the lesions were placed in the left hemisphere, and in three the lesions were placed in the right hemisphere. For each lesion, 1.5 mA anodal current was delivered for 25 s through a stainlesssteel insect pin (size 00) that was insulated except for 0.5 mm at the tip. With the skull level between bregma and lambda, the coordinates for the first
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lesion were 5.2 to 5.5 mm posterior from bregma, 1.1 mm lateral to the midline suture, and 3.3 mm below the dural surface. The second lesion was placed at the same lateral and depth coordinates but at 6.2 to 6.5 mm posterior to bregma. The coordinates for the third lesion were 7.2 to 7.5 mm posterior to bregma, 1.1 mm lateral to midline, and 2.2 mm below the dura mater. Control Operations. Eight animals had sham operations. The same procedure as that used for the SC lesions was followed except that no current was delivered. Lateral Hypothalamus Region (LH). For comparison, 10 animals received unilateral electrolytic lesions in either the left (n = 5) or right (n = 5) LH region. These lesions were aimed 2.5 mm anterior to the substantia nigra. As noted previously, electrolytic lesions aimed anterior to the substantia nigra yield an ipsiversive circling/postural bias (27). The effect of LH lesions on orienting and posture has been well established (l&25,27); whereas the effects on sensorimotor reactivity in the adhesive removal test have not been determined. The lesions were made by passing 1.2 mA anodal current through a stainless-steel insect pin (size 00) for 30 s, which reliably yields a contralateral sensorimotor deficit in standard tests of orienting behavior. Coordinates were 2.4 mm posterior to bregma, 1.9 mm lateral to midline, and 8.9 mm below the dura mater. Sensorimotor Cortex @MC). Eight animals received subtotal unilateral lesions of the SMC (five in the left hemisphere and three in the right). The lesions were aimed at the forepaw representation in the granular cortex, as defined by electrophysiologic recordings and intracortical microstimulation (3,8,2 1). A 2.2 X 2.0-mm rectangular area of skull and dura mater overlying the forepaw SMC was removed. The boundaries of this area were between 2.0 and 4.0 mm lateral to the midline suture, and between bregma and 2.2 mm anterior to bregma. A bare platinum electrode was lowered into one comer of the exposed cortex, 2 mm below the surface. Anodal current (1 mA) was delivered during eight equally spaced anterior-posterior traverses throughout the SMC. The total duration of current delivery was 120 s. The electrode was moved horizontally at an approximate speed of 0.15 mm/s. We have found that this method is remarkably more reliable than the suction technique in yielding hemorrhage-free cortical lesions of uniform shape and size in both the horizontal and vertical dimensions. Sensorimotor
Tests
Head Movement-Independent Orienting. Small adhesive-backed pieces of paper (manufactured by Avery International) of equal size ( 1.3 cm in diameter) were placed bilaterally on the radial aspect of the rat’s wrists. To attach the stimuli, the animal was taken out of its home cage for 5 to 10 s. The order
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of attachment (left vs right) was randomized. Immediately after the second adhesive patch was attached, the experimenter firmly touched both forelimbs simultaneously. The animal was then returned to its home cage, where responsivity is optimal. The cage was closed quietly to avoid distracting the animal. All sensorimotor and motor tests were administered both before and after surgery. Two to five separate trials were administered each test day. Stopwatches were started when the cage was closed. The latency to contact each stimulus with the mouth and the latency to remove each stimulus were recorded. In this task, an animal typically brings its forelimb to the mouth (contact) and removes the adhesive patch by using its teeth. Lateral head movements are not required [for a detailed description of this procedure see (24,27,28)]. A trial ended when the subject had removed both patches or after 3 mins. For each rat, the order of responding to one or the other stimulus (indicating an ipsilateral vs contralateral bias) was the primary measure of interest. The patches were discarded after each trial. Individual trials were separated by at least 3 min. In a follow-up test, for animals showing an ipsilateral bias, the size of the contralateral patch was incrementally increased, while the size of the ipsilateral patch was decreased. In previous work (24,26,28) we showed that when the contralateral patch is large enough relative to the ipsilateral patch, the response bias can be neutralized (the ipsilateral patch no longer is removed preferentially). The contralaterakipsilateral ratio necessary to balance the order of patch removal is regarded as an estimate of the magnitude of the asymmetry and may be assessed over time to indicate recovery of somatosensory function. Head Movement-Dependent Orienting. A cotton swab was used to provide light tactual stimulation to the snout, shoulders, or hindquarters (18, 35). Stimulus-dependent head and body-turning movements were recorded and rated according to a five-point scale (O-4). A score of 4 was assigned if the animal turned to bite the swab, a score of 3 if the animal turned and contacted the swab with the whiskers or snout; a turn without contact was a score of two; an incomplete turn toward the stimulus was rated as a score of one; and a zero was assigned if no response was elicited.
Postural/Motor Tests Spontaneous Circling. The rats were placed in Plexiglas bowl for 5 min and the number of 360” circles in each direction were noted. The bowl was rinsed with 95% alcohol and dried thoroughly after each test. Slanted Grid. The rats were placed on a 45” grid slope in three different positions: head down, ipsilateral side down, or contralateral side down. In
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the head-down position, the direction of turning 180” toward the upper part of the slope was noted ( 16). In the ipsi- and contralateral side down positions, the latency to turn 90” upward was noted. If the animal failed to respond within 120 s, the trial was ended and a maximum of 120 was scored for that trial. Also, if the animal failed initially to turn upward, and instead turned downward and continued in that direction by making a 270” turn, this was noted and a maximum score of 120 was assessed (sham controls did not do this, but in the immediate postoperative period SC animals frequently turned downward when the ipsilateral side faced down). Hang- Tail Test. The animals were picked up and briefly suspended by the base of the tail (for 1 to 3 s). The presence and direction of trunk flexion or rotation were noted (9,26). Histological
Analysis
All animals with lesions received an overdose of anesthesia and were perfused with saline followed by 10% Formalin. Their brains were extracted and frozen sections (40 pm) throughout the lesion were mounted and stained with cresyl violet. Analyses of lesion placement and size were aided by a Bausch and Lomb microprojector and the sections were compared with the K&rig and Klippel(12) and the Paxinos and Watson (22) rat brain atlases. Cortical lesions were compared also with Zilles’s atlas of the rat cortex (36). RESULTS Sensorimotor
Tests
Head Movement-Independent Orienting. Unilateral damage to the SC did not produce an ipsilateral sensorimotor asymmetry, as measured by the bilateral-stimulation (patch removal) test. Table 1 shows the mean percentage of trials on which the ipsilateral stimulus was removed first. Animals with SC lesions removed the ipsilateral stimulus first on 47.5 f 9.1% of the trials for the first 3 postoperative days (e.g., 42.0% 1 day after surgery and 50.0% 3 days after surgery) and on 18.7% of the trials 1 week after the lesion. ANOVA indicated that these data were not significantly different from preoperative values or from that of control animals on any of the test days. The median latency to remove the contralateral patch was slightly shorter than the median latency to remove the ipsilateral patch in animals with SC lesions, although this was not statistically significant. The interanimal scores were highly variable, as expected. In previous work, we found that order, rather than latency, of patch removal (ipsilateral vs contralateral) was the more reliable indicant of asymmetry (26-28). On the first postoperative test, the median latency to remove the ipsilateral patch was 23.5 s (range 4.0 to
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TABLE 1 Percentage of Trials That Ipsilateral Patch Was Removed First in Bilateral-Stimulation
Test”
Postoperative Lesion”
Preoperative
Days 1 and 3
Sham SC LH SMC
18.8+ 9.15 29.3 + 13.23 35.0 + 10.67 36.3 ?z 5.92
40.7 47.5 100.0 100.0
f 6.58 f 9.06 f o.oo* + o.oo*
Day I 37.5 * 18.7 f 12.2 f 100.0 +
15.66 13.15 14.70 o.oo*
’ Data are means + SE. * Abbreviations: SC-superior colliculus, LH-lateral hypothalamus, SMC-sensorimotor cortex. * Significantly different from Sham (P < 0.05) by ANOVA.
135.0 s) and the latency to remove the contralateral patch was 16 s (range 5.0 to 45.0 s). On the seventh postoperative day, the median ipsi- vs contralateral latencies were 7 s (range 4.5 to 101.0) vs 6.3 s (range 2.5 to 98.0). Recall that if an animal consistently favored the stimulus on either the left or right limb before surgery, the lesion or sham operation was placed in the hemisphere on the opposite side, so that postoperative lesion effects would not be masked by endogenous asymmetry. Because an effective lesion would tend to reverse any preoperative bias that might be present, these data suggest that the SC damage did not alter sensorimotor function. In contrast, all animals with unilateral LH or SMC lesions removed the ipsilateral patch first on all trials (Table I). Both groups were significantly different from controls, as indicated by ANOVA (P < 0.05). For the first 3 days, animals with SMC lesions removed the ipsilateral patch in a median of 2.5 s (range 1.5 to 9.5 s), which was significantly faster (P < 0.05) than for the contralateral patch (14.2 s; range 8.5 to 247.5 s). The contralaterakipsilateral stimulus ratio necessary to balance the asymmetry was 5.4: 1. That is, the contralateral stimulus needed to be more than five times as large as the ipsilateral stimulus to equalize responsiveness to the two stimuli. Animals with LH lesions removed the ipsilateral patch in 6.5 s (range 4.0 to 103.0 s), which was significantly faster (P < 0.05) than for the contralateral patch (75.0 s; range 12.0 to 180.0 s). The contralaterakipsilateral ratio for the LH group was 2.5: 1. On the 7th postoperative day, the ipsi- vs contralateral median latencies were 2.5 (range 1.0 to 4.5) vs 38.5 s (range 8.5 to 17 1.O) for the animals with SMC lesions (P < 0.05) and 17.8 (range 6.0 to 103.5) vs 103.3 s (range 3.5 to
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180.0) for the LH-damaged animals (P < 0.05). The contralateral:ipsilateral ratios did not change. All but one of the animals with SMC lesions continued to remove the ipsilateral patch first on all trials to 2 weeks after surgery. By 3 months, in four of the eight animals, this ipsilateral bias remained at lOO%, with a contralateral:ipsilateral ratio of 3.3: 1. The remaining four rats completely recovered. Neither the magnitude of the asymmetry nor the rate of recovery was associated differentially with damage to the left vs right hemisphere. Animals with sham operations showed no consistent asymmetry after surgery (Table 1). During the first 3 postoperative days, sham-operated animals removed the ipsilateral patch first on 40.6% of the trials. On the 1st day after surgery, these animals removed the ipsilateral patch in a median time of 9.0 s (range 2.5 to 67.5) and the contralateral patch in a median time of 14.0 s (range 2.0 to 93.5). Seven days after surgery, the median latency to remove the ipsilateral patch was 43.5 s (range 4.5 to 93.5) vs 15.8 s (range 3.0 to 96.5) for the contralateral patch. These were comparable to preoperative data. In separate tests, larger adhesive patches (2.0 cm in diameter) were placed bilaterally on the medial aspect of the hind limbs in the SC-damaged rats [see (27)]. Because normal rats typically use large lateral head and trunk movements to remove patches from the hind limbs, and because SC-damaged rats fail to make such movements toward the contralateral side, it seemed possible that they might consistently remove the ipsilateral patch first, or even neglect the contralateral patch altogether. Neither event occurred. The median percentage of trials on which the ipsilateral patch was removed first was 50.3%, which did not differ from that of the controls, at 53.5%. A change from the preoperative bias was observed in only 33% of SCdamaged animals. Of these, only one animal continued to exhibit an ipsilatera1 asymmetry for more than 5 days. Close examination of the movements used by all SC-damaged animals to remove the contralateral patch revealed that they were abnormal compared with the movements used to remove the ipsilateral patch. Response to the ipsilaterally placed patch usually involved a large lateral head movement, with minimal repositioning of the hind limb (the normal reaction). Responses to the contralateral stimulus involved a ventral head-tucking motion and a stretching of the hind limb forward to meet the mouth; no lateral movements occurred. The apparent difficulty in removing the adhesive patch from the contralateral hind limb did not affect the order of patch removal. Head Movement-Dependent Orienting. Behavioral data from representative postoperative days are shown in Table 2 for all groups. On the first postoperative test, all animals with SC lesions failed to make lateral head turns toward the cotton swab stimulus when it was placed anywhere on the contralateral side of the body. Considerable recovery followed. Head turns in re-
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TABLE 2 Head Movement-Dependent
Orienting”
Day 1 postoperative Shoulder
Snout Lesion b
Ipsi
Contra
Sham SC LH SMC
4.0 f .oo 3.5 f .22 3.8k.13 4.0 AZ.oo
4.0 z!z.oo 0.0 + .oo* 2.0 + .67* 3.3 + .67
4.0 3.3 3.9 4.0
Sham SC LH SMC
4.0 + .oo 3.4k.18 3.8 + .13 4.0 f .oo
4.0 + 1.5 f 3.3 + 4.0 f
Day 7 postoperative 4.0 * .oo 4.0 * .oo 3.4 + .18 0.6 + .38* 3.7 + .21 2.5 + .84* 3.5 + .50 3.5 + .50
.oo .60* .42 .oo
Ipsi
Hindquarters
+ + * *
Contra .oo .33 .I0 .oo
4.0 0.0 0.0 3.3
f f t f
a0 .oo* .oo* .67
Ipsi
Contra
3.5 + .50 2.0 Z!I.58 3.6 k .40 3.8 + .17
3.5 0.0 0.0 3.3
3.4 2.5 3.2 3.5
3.4 + .50 0.0 + .oo* 1.7 f .63* 3.5 f .50
+ .50 + .57 f .53 + .oo
k .50 * .oo* + .OOf k .67
a Data are means + SE. Highest score = 4; lowest score = 0. b Abbreviations as in Table 1. * Significantly different from Sham (P < 0.05) by ANOVA.
sponse to contralateral stimulation of the snout area were present in 40% of the animals 1 week after surgery, and all animals showed at least minimal responsiveness (i.e., a rating of at least 1.O) by 4 weeks (median: 10.5 days). The time course of recovery of the response to contralateral hindquarter stimulation was longer. No animal with an SC lesion showed even minimal responding to the hindquarters until 3 weeks postoperatively. At this time, 37.5% of the animals showed at least a small and brief contralateral head turn. This response was observed in all animals by 6 weeks after surgery (median: 5 weeks). As expected, animals with SC lesions made head turns in response to stimulation anywhere on the ipsilateral side of the body on all postoperative days studied. These responses were comparable to those made by animals in the sham control group to stimulation of either side. Animals with LH lesions failed to make head movements in response to contralateral tactile stimulation. On the first postoperative test, all animals neglected the tactile stimulus when it was placed on the shoulder or hindquarters, but only half of the animals neglected the stimulus when it was brushed along the snout. By the second postoperative test, all animals had recovered at least minimal head orienting to snout stimulation, but 25% still showed neglect to contralateral hindquarter stimulation. Note that the mag-
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StimulusIndependent
Circling”
Day 1 postoperative Lesion b Sham SC LH SMC
Ipsi turns 2.63 8.17 9.33 2.17
f 1.0 k 3.1* + 1.9* kO.8
Day 7 postoperative
Contra turns
Ipsi turns
Contra turns
2.13kO.5 1.42 f 0.8 0.17 kO.2 3.50 + 0.7
3.00 + 0.8 13.44 + 3.0* 5.67 k 1.6* 0.33 + 0.3
2.75 zk 0.6 1.11 kO.7 1.50 * 1.0 4.67 + 1.2*
’ Data are means + SE of numbers of turns per 5 min. b Abbreviations as in Table 1. * Significantly dil%rent from Sham (P < 0.05) by ANOVA.
nitude of the deficit and the duration of recovery from electrolytic LH lesions are known to be far less than that observed to follow severe GOHDA-induced damage to the nigrostriatal system ( 13- 18). Note also that in the present study, all sensorimotor tests were done in the closed home cage, where the probability of responding was greatest. In other locations, or even when the home cage was opened halfway, neglect of contralateral stimulation, including the snout, was observed, but responsiveness to ipsilateral stimulation was preserved [see also (26) for a related effect]. Lesions in the sensorimotor cortex produced no impairment in head movement-dependent orienting. Only one animal showed signs of a contralateral deficit 1 day after surgery. This impairment (rating = 0 on all body sites) was not apparent on any other postoperative day.
Postural/Motor Tests Stimulus-Independent Circling. As shown in Table 3, animals with SC or LH lesions circled in the Plexiglas bowl more frequently toward the side of the lesion. Control animals showed little or no preference for a direction of circling. This difference between lesion and control groups was statistically significant (P < 0.05). Animals with SMC lesions showed no preference for a direction of circling on the first postoperative test, but 1 week after surgery every animal circled contralaterally slightly more frequently than control animals (P < 0.05). Slant Grid Test.Animals with SC and LH lesions always turned 180” ipsilaterally when they were placed head down on the 45’ inclined grid. Animals with sham operations or SMC lesions showed no asymmetry. Control animals typically turned 90” upward when either the left or the right side of the
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TABLE 4 Slanted Grid Test” Day 1 postoperatively Lesion”
Ipsi side down
Sham SC LH SMC
8.76 f 73.63 + 104.90 f 27.16+
2.7 14.0* 8.4* 11.9
Day 7 postoperatively
Contra side down 7.26 12.58 9.34 18.22
+ + f f
Ipsi side down
1.4 5.7 2.6 7.4
29.44 53.92 73.71 7.49
+ + + +
Contra side down
9.6 15.3* 11.8* 2.9*
26.25 + 5.62 f 16.72+ 27.56 f
8.7 2.3* 5.2 13.4
’ Data are means + SE latencies to turn 90’ laterally and upward to face within lo’ of the top edge of the grid. b Abbreviations as in Table 1. * Significantly different from Sham (P < 0.05) by ANOVA.
body faced down slope. As shown in Table 4, animals with either SC or LH lesions readily made 90” ipsilateral turns when positioned such that the contralateral side of the body faced downward (mean latency to turn 90” on postoperative day 1: 12.58 s for the SC-damaged group and 9.3 s for the LH group). However, these same rats had difficulty in making 90“ contralateral turns toward the upper part of the slope when they were positioned such that their ipsilateral side faced downward (mean latency to turn 90” upward: 73.6 s for the SC group and 104.9 s for LH group). Indeed, on several occasions animals from the SC and LH lesion group turned 270” in the ipsilateral direction, rather than an upward 90” turn to the contralateral side. In sham-operated and SMC animals, there was no reliable difference between the mean latencies to make 90“ ipsilateral vs contralateral turns. TABLE 5 Percentage Flexes toward Ipsilateral Side a Days postoperative Le.sionb Sham SC LH SMC
1 40.63 80.00 86.00 33.33
+ 9.90 * I I .34* -+ 9.ao* f Il.15
a Data are means + SE. ’ For abbreviations see Table 1. * Significantly different from Sham (P < 0.05) by ANOVA.
7 53.57 68.75 43.75 36.67
zk 17.62 + 15.48 + 13.15 f 20.27
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FIG. I. Representative lesion in the superior colliculus (includes necrotic tissue as well as region of cavitation).
Hang-Tail Test. As shown in Table 5, animals in the SC or LH lesion groups flexed or rotated their trunks ipsilaterally on the majority of trials 1 day after surgery. However, unlike 6-OHDA-treated rats (27,28), this deficit was no longer apparent 1 week after the lesion. Animals with SMC lesions or or sham operations did not show any consistent asymmetry. None of the lesion groups differed significantly from controls. Histological
Analysis
Lesions of the Superior Colliculus. As shown in Fig. 1, all seven layers were destroyed in every animal throughout the anterior (5.8 mm posterior to bregma) and middle (6.8 mm posterior to bregma) aspects of the SC. In some animals, a small lateral patch of deep SC was spared, but only at the posterior border (7.8 mm posterior to bregma). In all cases, there was additional damage to the overlying cortex, hippocampus, pretectum, and central gray area. In two cases, the lesion extended into the brachium of the inferior colliculus,
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FIG. 2. Representative lesion in the lateral hypothalamic region (includes necrotic tissue as well as region of cavitation).
and in another case, into the underlying tegmentum. The mediodorsal nucleus of the thalamus was damaged in most cases. Lesions of the Lateral Hypothalamus. A representative lesion of the LH area is shown in Fig. 2. Lesions were typically large, and included the majority of the LH. Other brain regions showing significant damage included: zona incerta (n = 5), ventral tip of the internal capsule (n = 7), reticular nucleus of the thalamus (n = 4), nucleus basalis (n = 3), and the supraoptic decussations (n = 3). In some animals, there was slight damage to the medial and lateral thalamus (n = 4); subthalamic area (n = 3); medial hypothalamus (n = 2), or pars reticulata of the substantia nigra (n = 2). Lesions of the Sensorimotor Cortex. Sample cortical lesions are shown in Fig. 3. The damage included alI cortical layers and, in most cases, penetrated the corpus callosum. The underlying caudate and putamen were not directly damaged. According to the existing electrophysiologic maps of the SMC, the lesions extended from the upper forelimb representation in the posterior SMC to the wrist and forepaw representation in the granular cortex (3,8). In
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FIG. 3. Representative lesion in the forepaw areas of the sensorimotor cortex (includes necrotic tissue as well as region of cavitation).
most cases, these lesions also included the second forelimb area in the anterior agranular cortex, as described by Neafsey and Sievert (21). This latter area has been defined as a motor region which, when stimulated, elicits extension of the contralateral wrist and digits. The region between these areas, the agranular cortex which, when electrically stimulated, elicits vibrissae or neck movements, was also damaged. DISCUSSION As expected from earlier studies (14, 32), unilateral SC lesions impaired head movement-dependent contralateral orienting, and produced ipsiversive circling and postural asymmetries. However, SC lesions failed to produce asymmetry in the sensorimotor test that does not require large lateral head movements. The rats detected and localized tactile adhesive patches placed on the forelimb contralateral to the lesion and did not preferentially remove the ipsilateral patch first. When the adhesive patches were placed on the hind paws, the animals maintained preoperative response biases, even
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though the normal movement toward the contralateral patch was not carried out (response substitution). Thus, the effect of the SC lesions on somatosensory function was neutral. Previous observations of orienting in animals with bilateral SC lesions are consistent with these data (29,30,32). Cats with bilateral lesions continually direct their gaze downward and do not move their heads upward spontaneously or in response to visual stimuli; however, they can make delayed, presumably ventral, head movements in response to tactile stimuli placed on the dorsal aspect of the feet. Tactile reflexes of the head (i.e., eye closure in response to touch on the cornea) and limbs (i.e., forelimb placing) are normal (32). Hamsters with bilateral undercuts of the SC fail to orient to sunflower seeds placed in the visual fields, but orient if the sunflower seeds come in contact with the whiskers (29, 30). Those studies confirm that the SC is involved in visual orientation (7), but suggest that it does not mediate detection of tactile stimuli. Unilateral lesions in the LH region produced the well established asymmetries that are reliably measured using head movement-dependent orientation tests and stimulus-independent postural/circling tests ( 14, 18). In addition, unilateral LH lesions produced a reliable ipsilateral bias in the bilateral-stimulation test designed to assesssensorimotor function independently of postural, circling, or head movement asymmetries. These data are similar to those described in an earlier report on the effects of unilateral 6-OHDA-induced damage to the dopamine-containing projections of the nigrostriatal system, and of axon-sparing damage to the neostriatum (27,28). Lesions in the SMC produced a composite pattern of behavioral deficits that differed from that of any other lesion. Animals with these lesions showed no deficit or asymmetry in the head movement-dependent sensorimotor test, a consistent and large ipsilateral asymmetry on the bilateral-stimulation test, and a delayed tendency to circle spontaneously in a direction contralateral to the damage. Although it is difficult to reconcile the present study with electrophysiologic studies linking the deep SC layers with somatosensory function (34), an extensive review fails to support the idea that the SC plays a direct role in somatosensory function, independently of its role in the control of head movements (2). To evaluate the somatosensory function of the SC adequately, it will be necessary to compare moment-by-moment behavioral and neuronal activity in the freely moving animal (2,23). Note that we have not ruled out the possibility that SC lesions might cause some form of somatosensorimotor impairment. Many neurons in the SC show little or no activity during unimodal sensory stimulation but show enhanced activity in response to a somatosensory stimulus combined with a visual or auditory stimulus (19). Normal rats readily use somatosensory cues
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Summary of Sensorimotor Asymmetries That Follow Lesions of the Superior Colliculus (SC), Lateral Hypothalamic Region (LH), or Sensorimotor Cortex (SMC)
SC LH SMC
Head movementdependent orienting
Head movementindependent orienting
Ipsi Ipsi No bias
No bias Ipsi Ipsi
to facilitate localization of visual or auditory stimuli in space. It would be interesting to determine whether or not animals with SC damage would be able to benefit from such intermodal interactions after recovery from head movement deficits. Table 6 summarizes the sensorimotor effects of unilateral damage in the SC, SMC, and LH. Unilateral SC lesions, unlike LH or SMC lesions, did not yield a detectable sensorimotor asymmetry in the bilateral-stimulation test. However, the SC lesions caused a profound impairment of contralateral head movement that might well account for the orienting deficits reported by others who have used tests that do not distinguish sensorimotor from purely motor asymmetries. We conclude that the deep SC layers may be involved in motor control, and that any possible role in somatosensory function must be fundamentally different from that of the sensorimotor cortex or nigrostriatal systems. REFERENCES 1. BARTH, T. M., M. D. LINDNER, AND T. SCHALLERT. 1983. Sensorimotor asymmetries and tactile extinction in unilateral frontal cortex-damaged and striataI dopamine-depleted rats. Sot. Neurosci. Abstr. 9: 482. 2. BARTH, T. M., AND T. SCHALLERT. 1987. Multimodal sensorimotor function of the superior colliculus: A critical review. Submitted. 3. CHAPIN, J. K., AND C. LIN. 1984. Mapping the body representation in the Sl cortex of anesthetized and awake rats. J. Comp. Neural. 229: 199-2 13. 4. COOPER, R. M., B. H. BLAND, L. A. GILLESPIE, AND R. H. WHITAKER. 1970. Unilateral posterior cortical and unilateral collicular lesions and visually guided behavior in the rat. J. Comp. Physiol. Psycho/ 72: 286-295. 5. DUNNETT, S. B., D. M. LANE, AND P. WINN. 1985. Ibotenic acid lesions of the lateral hypothalamus: comparison with 6-hydroxydopamine-induced sensorimotor deficits. Neuroscience 14: 509-5 18. 6. EDWARDS, S. B., C. L. GINSBURGH, C. K. HENKEL, AND B. E. STEIN. 1979. Sources of subcortical projections to the superior colliculus in the cat. J. Comp. Neural. 184: 309330.
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M. A. 1983. Vision as a sensorimotor system. Pages 4 l-6 1 in T. E. ROBINSON, to Brain Research. Oxford Univ. Press, London/New York. HALL, R. D., AND E. P. LINDHOLM. 1974. Organization of motor and somatosensory neocortex in the albino rat. Brain Res. 66: 23-38. HOYMAN, L., G. D. WEESE, AND G. P. FROMMER. 1978. Tactile discrimination performance deficits following neglect-producing unilateral lateral hypothalamic lesions in the rat. Physiol. Behav. 22: 139- 147. K~RVEL, R. D., R. A. GREENFIELD, AND D. R. MEYER. 1974. Multimodal sensory neglect in rats with radical unilateral posterior isocortical and superior collicular ablations. J. Camp. Physiol. Psychol. 87: 156-162. KIRVEL, R. D. 1975. Sensorimotor responsiveness in rats with unilateral superior collicular and amygdaloid lesions. J. Comp. Physiol. Psychol. 89: 882-89 1. K~NIG, J. F. R., AND R. A. KLIPPEL. 1963. The Rat Brain: A Stereotaxic Atlas of the Forebrain and Lower Parts of the Brain Stem Williams & Wilkins, Baltimore. LIUNGBERG, T., AND U. UNGERSTEDT. 1976. Sensory inattention produced by 6-hydroxydopamine-induced degeneration of ascending dopamine neurons in the brain. Exp. NeuGOODALE,
Ed., BehavioralApproaches
8. 9. 10. 11. 12. 13.
rol. 53: 585-600.
14. MARSHALL, J. F. 1978. Comparison ofthe sensorimotor dysfunctions produced by damage to lateral hypothalamus or superior colliculus in the rat. Exp. Neurol. 58: 203-2 17. 15. MARSHALL, J. F. 1979. Somatosensory inattention after dopamine-depleting intracerebral 6-OHDA injection: spontaneous recovery and pharmacological control. Brain Res. 117: 31 l-324. 16. MARSHALL, J. F. 1980. Basal ganglia dopaminergic control of sensorimotor functions related to motivated behavior. Pages 167-176 in R. F. THOMPSON, L. H. HICKS, AND V. B. SHVYRKOV, Eds., Neural Mechanisms of Goal-Directed Behavior and Learning. Academic Press, New York. 17. MARSHALL, J. F., N. BERRIOS,AND S. SAWYER. 1980. Neostriatal dopamine and sensory inattention. J. Comp. Physiol. Psychol. 94: 833-846. 18. MARSHALL, J. F., B. H. TURNER, AND P. TEITELBAUM. 197 1. Sensory neglect produced by lateral hypothalamic damage. Science 18: 50-60. 19. MEREDITH, M. A., AND B. E. STEIN. 1983. Interactions among converging sensory inputs in the superior colliculus. Science 221: 389-39 1. 20. MITTELMAN, G., P. J. FRAY, AND E. S. VALENSTEIN. 1985. Asymmetry in the effects of unilateral 6-OHDA lesions on eating and drinking evoked by hypothalamic stimulation. Behav.
Brain
Res. 15: 263-267.
21. NEAFSEY, E. J., AND C. SIEVERT. 1982. A second forelimb area exists in the rat frontal cortex. Brain Res. 232: 15 1- 156. 22. PAXINOS, G., AND C. WATSON 1982. The Rat Brain in Stereotaxic Coordinates. Academic Press, New York. 23. RANCK, J. B., JR., J. L. KUBIE, S. E. Fox, S. WOLFSON, AND R. U. MULLER. 1983. Single neuron recording in behaving mammals: bridging the gap between neuronal events and sensory-behavior variables. Pages 62-93 in T. E. ROBINSON, Ed., Behavioral Approaches to Brain Research. Oxford University Press, London/New York. 24. SCHALLERT, T., T. D. HERNANDEZ, AND T. M. BARTH. 1986. Recovery of function after brain damage: severe and chronic disruption by diazepam. Brain Res. 379: 104- 111. 25. SCHALLERT, T., AND I. Q. WHISHAW. 1978. Two types of aphagia and two types of sensorimotor impairments after lateral hypothalamic lesions: observations in normal weight, dieted, and fattened rats. J. Comp. Physiol. Psychol. 92: 720-74 1. 26. SCHALLERT, T., AND I. Q. WHISHAW. 1984. Bilateral cutaneous stimulation ofthe somatosensory system in hemidecorticate rats. Behav. Neurosci. 98: 5 18-540.
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27. SCHALLERT, T., M. UPCHURCH, N. LOBAUGH, S. B. FARRAR, W. W. SPIRDUSO,P. GILLIAM, D. VAUGHN, AND R. E. WILCOX. 1982. Tactile extinction: distinguishing between sensorimotor and motor asymmetries in rats with unilateral nigrostriatal damage. Pharmacol. B&hem. Behav. 16: 455-462. 28. SCHALLERT, T., M. UPCHURCH, R. E. WILCOX, AND D. M. VAUGHN. 1983. Posture-independent sensorimotor analysis of inter-hemispheric receptor asymmetries in neostriaturn. Pharmacol. B&hem. Behav. 18: 753-759. 29. SCHNEIDER, G. E. 1967. Contrasting visuomotor functions of tectum and cortex in the golden hamster. Psychol. Forsch. 31: 52-62. 30. SCHNEIDER,G. E. 1969. Two visual systems. Brain mechanisms for localization and discrimination are disassociated by tectal and cortical lesions. Science 163: 895-902. 3 I. SPRAGUE, J. M. 1966. Interaction of cortex and superior colliculus in mediation of visually guided behavior in the cat. Science 153: 1544- 1547. 32. SPRAGUE, J. M., AND T. H. MEIKLE. 1965. The role of the superior colliculus in visuallyguided behavior. Exp. Neural. 11: 115-146. 33. STEIN, B. E. 1984. Multimodal representation in the superior colliculus and optic tectum. Pages 8 19-84 I in H. VANEGAS, Ed., Comparative Neurology of the Optic Tectum. Plenum, New York. 34. STEIN, B. E., B. MAGALHAES-CASTRO, AND L. KRUGER. 1976. Relationship between visual and tactile representations in cat superior colliculus. J. Neurophysiol. 39: 40 l-4 19. 35. WHISHAW, I. Q., T. SCHALLERT, AND B. KOLB. 198 1. An analysis offeeding and sensorimotor abilities of rats after decortication. J. Comp. Physiol. Psychol. 95: 85-103. 36. ZILLES, K. 1985. The Cortex of the Rut. Springer-Verlag, New York.
NEUROLOGY
95,66 I-678 (I 987)
Somatosensorimotor Function of the Superior Colliculus, Somatosensory Cortex, and Lateral Hypothalamus in the Rat T. M. BARTH AND T. SCHALLERT’ Department of Psychology and Institute for Neurological Science, University of Texas, Austin, Texas 78712 Received June 13, 1986; revision received September IS, I986 The role of the superior colliculus in multimodal sensory function is unsettled, in large part because a clear distinction between the somatosensory effects and the postural/motor effects of damage to the deep layers of the superior colliculus has not been obtained. Unilateral lesions of the entire superior colliculus impair orienting of the head and eyes to tactile, visual, and auditory stimuli presented on the side of the body contralateral to the lesion; however, even in the absence of sensory stimulation animals with such a lesion tend to circle ipsiversively and fail to make contralateral head movements. To determine whether or not unilateral damage to the superior colliculus produces a somatosensory asymmetry independently of head movement/ circling biases, a neurological test was used in which lateral head or trunk movements were not required. Small pieces of adhesive-backed paper were attached to each forelimb and the latencies to contact and remove the stimuli were recorded. A battery of standard neurological tests was administered as well. The entire superior colliculus was removed unilaterally, and for comparison, the sensorimotor cortex or lateral hypothalamus were damaged in additional groups. Lesions of the superior colliculus produced the expected deficit in contralateral orienting and ipsilateral circling/pastural biases, but failed to produce a somatosensory asymmetry in the head movementindependent sensorimotor test. In contrast, both sensorimotor cortex and lateral hypothalamus lesions produced a severe asymmetry in the head-movement-independent sensorimotor test. We conclude that the superior colhculus is involved in the control of lateral head movements and that its role in somatosensory function is fundamentally different from that of the sensorimotor cortex or lateral hypothalamus regions. 0 1987 Academic Press. Inc.
Abbreviations: LH--lateral hypothalamus, 6-OHDA-6-hydroxydopamine, SC-superior colliculus, SMC-sensorimotor cortex. ’ This work was supported by funds from National Institutes of Health grants NS 17274 and NS23964 to T.S. We thank Theresa Dea Hemandez, Gary Knight, Don Goemer, and David Heard. Please address correspondence to Dr. Timothy Schallert.
0014-4886187 $3.00 Copyright 0 1987 by Academic Press, Inc. All rights of reproduction in any form reserved.
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INTRODUCTION The superior colliculus (SC), particularly the deep layers, are thought to be involved in multimodal sensory function (6,33). After unilateral ablation of the SC, rats and cats do not orient the head or eyes toward visual, auditory, olfactory, or tactile stimuli presented on the side of the body contralateral to the lesion and show normal or exaggerated orienting responses to stimuli in the ipsilateral sensory field or near midline (10, 11, 14, 3 1, 32). Some investigators have suggested that the orienting deficit may be directly related to a movement/postural asymmetry, rather than to a sensory dysfunction or to an impairment in sensorimotor integration (4, 14). Even in the absence of sensory stimulation, animals with unilateral SC lesions tend to circle toward the side of the damage and fail to make spontaneous contralateral head scans (4, 14,32). It remains unclear whether or not these animals possess the ability to detect and localize contralateral tactile stimuli. In recent work a behavioral task was developed to measure sensorimotor asymmetries independently of postural and head movement asymmetries in rats with unilateral lesions of the nigrostriatal system (27, 28) or neocortex ( 1,26). In this task, lateral head or trunk movements are not required. This is important because animals with 6-hydroxydopamine (6-OHDA)-induced depletion of striatal dopamine fail to make lateral head movements toward stimuli, such as a von Frey hair, applied to the contralateral side of the body [a deficit known as neglect or inattention (13, 15, 17, 18)]. Small pieces of adhesive paper are placed on the radial aspects of the wrists of each forelimb (bilaterally and simultaneously). The rat lifts each forelimb to the mouth to remove the adhesive patches, one at a time. Prior to surgery, rats may show a left, right, or no bias. After unilateral 6-OHDA-induced depletion of striatal dopaminergic neurons, rats always remove the ipsilateral adhesive patch first, followed by the contralateral adhesive patch [an ipsilateral sensorimotor bias (1, 5, 20, 27)]. The contralateral stimulus is rarely neglected, which is consistent with the view that in addition to asymmetrical sensory reactivity, motor dysfunction (particularly a deficit in the initiation of contralateral head movements) may contribute to the contralateral neglect observed in standard orientation tests. Motor and sensorimotor asymmetries can be dissociated by comparing the effects of electrolytic lesion-induced ablation of the substantia nigra vs unilateral infusions of 6-OHDA into the nigrostriatal system at a level anterior to the substantia nigra. Animals with 6-OHDA lesions show ipsiversive circling and postural asymmetry and fail to make contraversive lateral head turns, whereas animals with electrolytic lesions in substantia nigra show spontaneous contruversive circling and postural asymmetry and fail to make ipsiversive lateral head turns [(27) for review]. However, in the bilateral-stimulation test, after both types of lesion, the animals respond to the ipszlateral
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stimulus first on all trials. Presumably, this ipsilateral sensorimotor bias, which was detectable only by means of the bilateral-stimulation test, stemmed from common damage to the ascending dopaminergic nigrostriatal system in both groups, whereas the contraversive motor bias observed in rats sustaining electrolytic lesions of the substantia nigra was due to additional damage to caudal projections from the substantia nigra or to other nondopaminergic neurons (28). In the present study, the bilateral-stimulation test was used to determine whether or not rats with unilateral SC lesions have a sensorimotor asymmetry independent of the well known head movement/circling bias. For comparison, two previously untested groups were examined, including animals with unilateral electrolytic damage to the lateral hypothalamic region (LH; in the vicinity of ascending nigrostriatal neurons) and animals with damage to the sensorimotor cortex (SMC; aimed at the forelimb area). METHODS Animals Thirty-eight male Long Evans hooded rats, 3 to 6 months old and weighing 300 to 500 g, were randomly selected from our laboratory breeding colony. All rats were gently handled 10 min/day (or longer when necessary to establish obvious tameness) for 2 weeks before preoperative behavioral testing. The animals were maintained on a 12-h light: 12 h dark cycle with food and water freely available. Testing took place during the light portion of the cycle. Five animals were housed in individual Plexiglas cages and the remaining 27 were maintained in individual wire-mesh cages. Surgery All lesions were unilateral. The choice of hemisphere (left or right) was based on preoperative performance in the patch removal test (detailed below). For example, if the stimulus on the left limb was removed first on more than 50% of the trials, the lesions were placed in the right hemisphere, so that any lesion-induced change would be detectable beyond the endogenous asymmetry. Superior Colliculus. Ten animals were anesthetized with Equithesin (0.3 ml/100 g) and received three overlapping lesions in the superior colliculus in one hemisphere. In seven animals, the lesions were placed in the left hemisphere, and in three the lesions were placed in the right hemisphere. For each lesion, 1.5 mA anodal current was delivered for 25 s through a stainlesssteel insect pin (size 00) that was insulated except for 0.5 mm at the tip. With the skull level between bregma and lambda, the coordinates for the first
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lesion were 5.2 to 5.5 mm posterior from bregma, 1.1 mm lateral to the midline suture, and 3.3 mm below the dural surface. The second lesion was placed at the same lateral and depth coordinates but at 6.2 to 6.5 mm posterior to bregma. The coordinates for the third lesion were 7.2 to 7.5 mm posterior to bregma, 1.1 mm lateral to midline, and 2.2 mm below the dura mater. Control Operations. Eight animals had sham operations. The same procedure as that used for the SC lesions was followed except that no current was delivered. Lateral Hypothalamus Region (LH). For comparison, 10 animals received unilateral electrolytic lesions in either the left (n = 5) or right (n = 5) LH region. These lesions were aimed 2.5 mm anterior to the substantia nigra. As noted previously, electrolytic lesions aimed anterior to the substantia nigra yield an ipsiversive circling/postural bias (27). The effect of LH lesions on orienting and posture has been well established (l&25,27); whereas the effects on sensorimotor reactivity in the adhesive removal test have not been determined. The lesions were made by passing 1.2 mA anodal current through a stainless-steel insect pin (size 00) for 30 s, which reliably yields a contralateral sensorimotor deficit in standard tests of orienting behavior. Coordinates were 2.4 mm posterior to bregma, 1.9 mm lateral to midline, and 8.9 mm below the dura mater. Sensorimotor Cortex @MC). Eight animals received subtotal unilateral lesions of the SMC (five in the left hemisphere and three in the right). The lesions were aimed at the forepaw representation in the granular cortex, as defined by electrophysiologic recordings and intracortical microstimulation (3,8,2 1). A 2.2 X 2.0-mm rectangular area of skull and dura mater overlying the forepaw SMC was removed. The boundaries of this area were between 2.0 and 4.0 mm lateral to the midline suture, and between bregma and 2.2 mm anterior to bregma. A bare platinum electrode was lowered into one comer of the exposed cortex, 2 mm below the surface. Anodal current (1 mA) was delivered during eight equally spaced anterior-posterior traverses throughout the SMC. The total duration of current delivery was 120 s. The electrode was moved horizontally at an approximate speed of 0.15 mm/s. We have found that this method is remarkably more reliable than the suction technique in yielding hemorrhage-free cortical lesions of uniform shape and size in both the horizontal and vertical dimensions. Sensorimotor
Tests
Head Movement-Independent Orienting. Small adhesive-backed pieces of paper (manufactured by Avery International) of equal size ( 1.3 cm in diameter) were placed bilaterally on the radial aspect of the rat’s wrists. To attach the stimuli, the animal was taken out of its home cage for 5 to 10 s. The order
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of attachment (left vs right) was randomized. Immediately after the second adhesive patch was attached, the experimenter firmly touched both forelimbs simultaneously. The animal was then returned to its home cage, where responsivity is optimal. The cage was closed quietly to avoid distracting the animal. All sensorimotor and motor tests were administered both before and after surgery. Two to five separate trials were administered each test day. Stopwatches were started when the cage was closed. The latency to contact each stimulus with the mouth and the latency to remove each stimulus were recorded. In this task, an animal typically brings its forelimb to the mouth (contact) and removes the adhesive patch by using its teeth. Lateral head movements are not required [for a detailed description of this procedure see (24,27,28)]. A trial ended when the subject had removed both patches or after 3 mins. For each rat, the order of responding to one or the other stimulus (indicating an ipsilateral vs contralateral bias) was the primary measure of interest. The patches were discarded after each trial. Individual trials were separated by at least 3 min. In a follow-up test, for animals showing an ipsilateral bias, the size of the contralateral patch was incrementally increased, while the size of the ipsilateral patch was decreased. In previous work (24,26,28) we showed that when the contralateral patch is large enough relative to the ipsilateral patch, the response bias can be neutralized (the ipsilateral patch no longer is removed preferentially). The contralaterakipsilateral ratio necessary to balance the order of patch removal is regarded as an estimate of the magnitude of the asymmetry and may be assessed over time to indicate recovery of somatosensory function. Head Movement-Dependent Orienting. A cotton swab was used to provide light tactual stimulation to the snout, shoulders, or hindquarters (18, 35). Stimulus-dependent head and body-turning movements were recorded and rated according to a five-point scale (O-4). A score of 4 was assigned if the animal turned to bite the swab, a score of 3 if the animal turned and contacted the swab with the whiskers or snout; a turn without contact was a score of two; an incomplete turn toward the stimulus was rated as a score of one; and a zero was assigned if no response was elicited.
Postural/Motor Tests Spontaneous Circling. The rats were placed in Plexiglas bowl for 5 min and the number of 360” circles in each direction were noted. The bowl was rinsed with 95% alcohol and dried thoroughly after each test. Slanted Grid. The rats were placed on a 45” grid slope in three different positions: head down, ipsilateral side down, or contralateral side down. In
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the head-down position, the direction of turning 180” toward the upper part of the slope was noted ( 16). In the ipsi- and contralateral side down positions, the latency to turn 90” upward was noted. If the animal failed to respond within 120 s, the trial was ended and a maximum of 120 was scored for that trial. Also, if the animal failed initially to turn upward, and instead turned downward and continued in that direction by making a 270” turn, this was noted and a maximum score of 120 was assessed (sham controls did not do this, but in the immediate postoperative period SC animals frequently turned downward when the ipsilateral side faced down). Hang- Tail Test. The animals were picked up and briefly suspended by the base of the tail (for 1 to 3 s). The presence and direction of trunk flexion or rotation were noted (9,26). Histological
Analysis
All animals with lesions received an overdose of anesthesia and were perfused with saline followed by 10% Formalin. Their brains were extracted and frozen sections (40 pm) throughout the lesion were mounted and stained with cresyl violet. Analyses of lesion placement and size were aided by a Bausch and Lomb microprojector and the sections were compared with the K&rig and Klippel(12) and the Paxinos and Watson (22) rat brain atlases. Cortical lesions were compared also with Zilles’s atlas of the rat cortex (36). RESULTS Sensorimotor
Tests
Head Movement-Independent Orienting. Unilateral damage to the SC did not produce an ipsilateral sensorimotor asymmetry, as measured by the bilateral-stimulation (patch removal) test. Table 1 shows the mean percentage of trials on which the ipsilateral stimulus was removed first. Animals with SC lesions removed the ipsilateral stimulus first on 47.5 f 9.1% of the trials for the first 3 postoperative days (e.g., 42.0% 1 day after surgery and 50.0% 3 days after surgery) and on 18.7% of the trials 1 week after the lesion. ANOVA indicated that these data were not significantly different from preoperative values or from that of control animals on any of the test days. The median latency to remove the contralateral patch was slightly shorter than the median latency to remove the ipsilateral patch in animals with SC lesions, although this was not statistically significant. The interanimal scores were highly variable, as expected. In previous work, we found that order, rather than latency, of patch removal (ipsilateral vs contralateral) was the more reliable indicant of asymmetry (26-28). On the first postoperative test, the median latency to remove the ipsilateral patch was 23.5 s (range 4.0 to
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TABLE 1 Percentage of Trials That Ipsilateral Patch Was Removed First in Bilateral-Stimulation
Test”
Postoperative Lesion”
Preoperative
Days 1 and 3
Sham SC LH SMC
18.8+ 9.15 29.3 + 13.23 35.0 + 10.67 36.3 ?z 5.92
40.7 47.5 100.0 100.0
f 6.58 f 9.06 f o.oo* + o.oo*
Day I 37.5 * 18.7 f 12.2 f 100.0 +
15.66 13.15 14.70 o.oo*
’ Data are means + SE. * Abbreviations: SC-superior colliculus, LH-lateral hypothalamus, SMC-sensorimotor cortex. * Significantly different from Sham (P < 0.05) by ANOVA.
135.0 s) and the latency to remove the contralateral patch was 16 s (range 5.0 to 45.0 s). On the seventh postoperative day, the median ipsi- vs contralateral latencies were 7 s (range 4.5 to 101.0) vs 6.3 s (range 2.5 to 98.0). Recall that if an animal consistently favored the stimulus on either the left or right limb before surgery, the lesion or sham operation was placed in the hemisphere on the opposite side, so that postoperative lesion effects would not be masked by endogenous asymmetry. Because an effective lesion would tend to reverse any preoperative bias that might be present, these data suggest that the SC damage did not alter sensorimotor function. In contrast, all animals with unilateral LH or SMC lesions removed the ipsilateral patch first on all trials (Table I). Both groups were significantly different from controls, as indicated by ANOVA (P < 0.05). For the first 3 days, animals with SMC lesions removed the ipsilateral patch in a median of 2.5 s (range 1.5 to 9.5 s), which was significantly faster (P < 0.05) than for the contralateral patch (14.2 s; range 8.5 to 247.5 s). The contralaterakipsilateral stimulus ratio necessary to balance the asymmetry was 5.4: 1. That is, the contralateral stimulus needed to be more than five times as large as the ipsilateral stimulus to equalize responsiveness to the two stimuli. Animals with LH lesions removed the ipsilateral patch in 6.5 s (range 4.0 to 103.0 s), which was significantly faster (P < 0.05) than for the contralateral patch (75.0 s; range 12.0 to 180.0 s). The contralaterakipsilateral ratio for the LH group was 2.5: 1. On the 7th postoperative day, the ipsi- vs contralateral median latencies were 2.5 (range 1.0 to 4.5) vs 38.5 s (range 8.5 to 17 1.O) for the animals with SMC lesions (P < 0.05) and 17.8 (range 6.0 to 103.5) vs 103.3 s (range 3.5 to
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180.0) for the LH-damaged animals (P < 0.05). The contralateral:ipsilateral ratios did not change. All but one of the animals with SMC lesions continued to remove the ipsilateral patch first on all trials to 2 weeks after surgery. By 3 months, in four of the eight animals, this ipsilateral bias remained at lOO%, with a contralateral:ipsilateral ratio of 3.3: 1. The remaining four rats completely recovered. Neither the magnitude of the asymmetry nor the rate of recovery was associated differentially with damage to the left vs right hemisphere. Animals with sham operations showed no consistent asymmetry after surgery (Table 1). During the first 3 postoperative days, sham-operated animals removed the ipsilateral patch first on 40.6% of the trials. On the 1st day after surgery, these animals removed the ipsilateral patch in a median time of 9.0 s (range 2.5 to 67.5) and the contralateral patch in a median time of 14.0 s (range 2.0 to 93.5). Seven days after surgery, the median latency to remove the ipsilateral patch was 43.5 s (range 4.5 to 93.5) vs 15.8 s (range 3.0 to 96.5) for the contralateral patch. These were comparable to preoperative data. In separate tests, larger adhesive patches (2.0 cm in diameter) were placed bilaterally on the medial aspect of the hind limbs in the SC-damaged rats [see (27)]. Because normal rats typically use large lateral head and trunk movements to remove patches from the hind limbs, and because SC-damaged rats fail to make such movements toward the contralateral side, it seemed possible that they might consistently remove the ipsilateral patch first, or even neglect the contralateral patch altogether. Neither event occurred. The median percentage of trials on which the ipsilateral patch was removed first was 50.3%, which did not differ from that of the controls, at 53.5%. A change from the preoperative bias was observed in only 33% of SCdamaged animals. Of these, only one animal continued to exhibit an ipsilatera1 asymmetry for more than 5 days. Close examination of the movements used by all SC-damaged animals to remove the contralateral patch revealed that they were abnormal compared with the movements used to remove the ipsilateral patch. Response to the ipsilaterally placed patch usually involved a large lateral head movement, with minimal repositioning of the hind limb (the normal reaction). Responses to the contralateral stimulus involved a ventral head-tucking motion and a stretching of the hind limb forward to meet the mouth; no lateral movements occurred. The apparent difficulty in removing the adhesive patch from the contralateral hind limb did not affect the order of patch removal. Head Movement-Dependent Orienting. Behavioral data from representative postoperative days are shown in Table 2 for all groups. On the first postoperative test, all animals with SC lesions failed to make lateral head turns toward the cotton swab stimulus when it was placed anywhere on the contralateral side of the body. Considerable recovery followed. Head turns in re-
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TABLE 2 Head Movement-Dependent
Orienting”
Day 1 postoperative Shoulder
Snout Lesion b
Ipsi
Contra
Sham SC LH SMC
4.0 f .oo 3.5 f .22 3.8k.13 4.0 AZ.oo
4.0 z!z.oo 0.0 + .oo* 2.0 + .67* 3.3 + .67
4.0 3.3 3.9 4.0
Sham SC LH SMC
4.0 + .oo 3.4k.18 3.8 + .13 4.0 f .oo
4.0 + 1.5 f 3.3 + 4.0 f
Day 7 postoperative 4.0 * .oo 4.0 * .oo 3.4 + .18 0.6 + .38* 3.7 + .21 2.5 + .84* 3.5 + .50 3.5 + .50
.oo .60* .42 .oo
Ipsi
Hindquarters
+ + * *
Contra .oo .33 .I0 .oo
4.0 0.0 0.0 3.3
f f t f
a0 .oo* .oo* .67
Ipsi
Contra
3.5 + .50 2.0 Z!I.58 3.6 k .40 3.8 + .17
3.5 0.0 0.0 3.3
3.4 2.5 3.2 3.5
3.4 + .50 0.0 + .oo* 1.7 f .63* 3.5 f .50
+ .50 + .57 f .53 + .oo
k .50 * .oo* + .OOf k .67
a Data are means + SE. Highest score = 4; lowest score = 0. b Abbreviations as in Table 1. * Significantly different from Sham (P < 0.05) by ANOVA.
sponse to contralateral stimulation of the snout area were present in 40% of the animals 1 week after surgery, and all animals showed at least minimal responsiveness (i.e., a rating of at least 1.O) by 4 weeks (median: 10.5 days). The time course of recovery of the response to contralateral hindquarter stimulation was longer. No animal with an SC lesion showed even minimal responding to the hindquarters until 3 weeks postoperatively. At this time, 37.5% of the animals showed at least a small and brief contralateral head turn. This response was observed in all animals by 6 weeks after surgery (median: 5 weeks). As expected, animals with SC lesions made head turns in response to stimulation anywhere on the ipsilateral side of the body on all postoperative days studied. These responses were comparable to those made by animals in the sham control group to stimulation of either side. Animals with LH lesions failed to make head movements in response to contralateral tactile stimulation. On the first postoperative test, all animals neglected the tactile stimulus when it was placed on the shoulder or hindquarters, but only half of the animals neglected the stimulus when it was brushed along the snout. By the second postoperative test, all animals had recovered at least minimal head orienting to snout stimulation, but 25% still showed neglect to contralateral hindquarter stimulation. Note that the mag-
670
BARTH
AND SCHALLERT TABLE 3
StimulusIndependent
Circling”
Day 1 postoperative Lesion b Sham SC LH SMC
Ipsi turns 2.63 8.17 9.33 2.17
f 1.0 k 3.1* + 1.9* kO.8
Day 7 postoperative
Contra turns
Ipsi turns
Contra turns
2.13kO.5 1.42 f 0.8 0.17 kO.2 3.50 + 0.7
3.00 + 0.8 13.44 + 3.0* 5.67 k 1.6* 0.33 + 0.3
2.75 zk 0.6 1.11 kO.7 1.50 * 1.0 4.67 + 1.2*
’ Data are means + SE of numbers of turns per 5 min. b Abbreviations as in Table 1. * Significantly dil%rent from Sham (P < 0.05) by ANOVA.
nitude of the deficit and the duration of recovery from electrolytic LH lesions are known to be far less than that observed to follow severe GOHDA-induced damage to the nigrostriatal system ( 13- 18). Note also that in the present study, all sensorimotor tests were done in the closed home cage, where the probability of responding was greatest. In other locations, or even when the home cage was opened halfway, neglect of contralateral stimulation, including the snout, was observed, but responsiveness to ipsilateral stimulation was preserved [see also (26) for a related effect]. Lesions in the sensorimotor cortex produced no impairment in head movement-dependent orienting. Only one animal showed signs of a contralateral deficit 1 day after surgery. This impairment (rating = 0 on all body sites) was not apparent on any other postoperative day.
Postural/Motor Tests Stimulus-Independent Circling. As shown in Table 3, animals with SC or LH lesions circled in the Plexiglas bowl more frequently toward the side of the lesion. Control animals showed little or no preference for a direction of circling. This difference between lesion and control groups was statistically significant (P < 0.05). Animals with SMC lesions showed no preference for a direction of circling on the first postoperative test, but 1 week after surgery every animal circled contralaterally slightly more frequently than control animals (P < 0.05). Slant Grid Test.Animals with SC and LH lesions always turned 180” ipsilaterally when they were placed head down on the 45’ inclined grid. Animals with sham operations or SMC lesions showed no asymmetry. Control animals typically turned 90” upward when either the left or the right side of the
BRAIN REGIONS AND SENSORIMOTOR
671
FUNCTION
TABLE 4 Slanted Grid Test” Day 1 postoperatively Lesion”
Ipsi side down
Sham SC LH SMC
8.76 f 73.63 + 104.90 f 27.16+
2.7 14.0* 8.4* 11.9
Day 7 postoperatively
Contra side down 7.26 12.58 9.34 18.22
+ + f f
Ipsi side down
1.4 5.7 2.6 7.4
29.44 53.92 73.71 7.49
+ + + +
Contra side down
9.6 15.3* 11.8* 2.9*
26.25 + 5.62 f 16.72+ 27.56 f
8.7 2.3* 5.2 13.4
’ Data are means + SE latencies to turn 90’ laterally and upward to face within lo’ of the top edge of the grid. b Abbreviations as in Table 1. * Significantly different from Sham (P < 0.05) by ANOVA.
body faced down slope. As shown in Table 4, animals with either SC or LH lesions readily made 90” ipsilateral turns when positioned such that the contralateral side of the body faced downward (mean latency to turn 90” on postoperative day 1: 12.58 s for the SC-damaged group and 9.3 s for the LH group). However, these same rats had difficulty in making 90“ contralateral turns toward the upper part of the slope when they were positioned such that their ipsilateral side faced downward (mean latency to turn 90” upward: 73.6 s for the SC group and 104.9 s for LH group). Indeed, on several occasions animals from the SC and LH lesion group turned 270” in the ipsilateral direction, rather than an upward 90” turn to the contralateral side. In sham-operated and SMC animals, there was no reliable difference between the mean latencies to make 90“ ipsilateral vs contralateral turns. TABLE 5 Percentage Flexes toward Ipsilateral Side a Days postoperative Le.sionb Sham SC LH SMC
1 40.63 80.00 86.00 33.33
+ 9.90 * I I .34* -+ 9.ao* f Il.15
a Data are means + SE. ’ For abbreviations see Table 1. * Significantly different from Sham (P < 0.05) by ANOVA.
7 53.57 68.75 43.75 36.67
zk 17.62 + 15.48 + 13.15 f 20.27
672
BARTH
AND SCHALLERT
FIG. I. Representative lesion in the superior colliculus (includes necrotic tissue as well as region of cavitation).
Hang-Tail Test. As shown in Table 5, animals in the SC or LH lesion groups flexed or rotated their trunks ipsilaterally on the majority of trials 1 day after surgery. However, unlike 6-OHDA-treated rats (27,28), this deficit was no longer apparent 1 week after the lesion. Animals with SMC lesions or or sham operations did not show any consistent asymmetry. None of the lesion groups differed significantly from controls. Histological
Analysis
Lesions of the Superior Colliculus. As shown in Fig. 1, all seven layers were destroyed in every animal throughout the anterior (5.8 mm posterior to bregma) and middle (6.8 mm posterior to bregma) aspects of the SC. In some animals, a small lateral patch of deep SC was spared, but only at the posterior border (7.8 mm posterior to bregma). In all cases, there was additional damage to the overlying cortex, hippocampus, pretectum, and central gray area. In two cases, the lesion extended into the brachium of the inferior colliculus,
BRAIN REGIONS AND SENSORIMOTOR
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673
FIG. 2. Representative lesion in the lateral hypothalamic region (includes necrotic tissue as well as region of cavitation).
and in another case, into the underlying tegmentum. The mediodorsal nucleus of the thalamus was damaged in most cases. Lesions of the Lateral Hypothalamus. A representative lesion of the LH area is shown in Fig. 2. Lesions were typically large, and included the majority of the LH. Other brain regions showing significant damage included: zona incerta (n = 5), ventral tip of the internal capsule (n = 7), reticular nucleus of the thalamus (n = 4), nucleus basalis (n = 3), and the supraoptic decussations (n = 3). In some animals, there was slight damage to the medial and lateral thalamus (n = 4); subthalamic area (n = 3); medial hypothalamus (n = 2), or pars reticulata of the substantia nigra (n = 2). Lesions of the Sensorimotor Cortex. Sample cortical lesions are shown in Fig. 3. The damage included alI cortical layers and, in most cases, penetrated the corpus callosum. The underlying caudate and putamen were not directly damaged. According to the existing electrophysiologic maps of the SMC, the lesions extended from the upper forelimb representation in the posterior SMC to the wrist and forepaw representation in the granular cortex (3,8). In
674
BARTH
AND SCHALLERT
FIG. 3. Representative lesion in the forepaw areas of the sensorimotor cortex (includes necrotic tissue as well as region of cavitation).
most cases, these lesions also included the second forelimb area in the anterior agranular cortex, as described by Neafsey and Sievert (21). This latter area has been defined as a motor region which, when stimulated, elicits extension of the contralateral wrist and digits. The region between these areas, the agranular cortex which, when electrically stimulated, elicits vibrissae or neck movements, was also damaged. DISCUSSION As expected from earlier studies (14, 32), unilateral SC lesions impaired head movement-dependent contralateral orienting, and produced ipsiversive circling and postural asymmetries. However, SC lesions failed to produce asymmetry in the sensorimotor test that does not require large lateral head movements. The rats detected and localized tactile adhesive patches placed on the forelimb contralateral to the lesion and did not preferentially remove the ipsilateral patch first. When the adhesive patches were placed on the hind paws, the animals maintained preoperative response biases, even
BRAIN REGIONS AND SENSORiMOTOR
FUNCTION
675
though the normal movement toward the contralateral patch was not carried out (response substitution). Thus, the effect of the SC lesions on somatosensory function was neutral. Previous observations of orienting in animals with bilateral SC lesions are consistent with these data (29,30,32). Cats with bilateral lesions continually direct their gaze downward and do not move their heads upward spontaneously or in response to visual stimuli; however, they can make delayed, presumably ventral, head movements in response to tactile stimuli placed on the dorsal aspect of the feet. Tactile reflexes of the head (i.e., eye closure in response to touch on the cornea) and limbs (i.e., forelimb placing) are normal (32). Hamsters with bilateral undercuts of the SC fail to orient to sunflower seeds placed in the visual fields, but orient if the sunflower seeds come in contact with the whiskers (29, 30). Those studies confirm that the SC is involved in visual orientation (7), but suggest that it does not mediate detection of tactile stimuli. Unilateral lesions in the LH region produced the well established asymmetries that are reliably measured using head movement-dependent orientation tests and stimulus-independent postural/circling tests ( 14, 18). In addition, unilateral LH lesions produced a reliable ipsilateral bias in the bilateral-stimulation test designed to assesssensorimotor function independently of postural, circling, or head movement asymmetries. These data are similar to those described in an earlier report on the effects of unilateral 6-OHDA-induced damage to the dopamine-containing projections of the nigrostriatal system, and of axon-sparing damage to the neostriatum (27,28). Lesions in the SMC produced a composite pattern of behavioral deficits that differed from that of any other lesion. Animals with these lesions showed no deficit or asymmetry in the head movement-dependent sensorimotor test, a consistent and large ipsilateral asymmetry on the bilateral-stimulation test, and a delayed tendency to circle spontaneously in a direction contralateral to the damage. Although it is difficult to reconcile the present study with electrophysiologic studies linking the deep SC layers with somatosensory function (34), an extensive review fails to support the idea that the SC plays a direct role in somatosensory function, independently of its role in the control of head movements (2). To evaluate the somatosensory function of the SC adequately, it will be necessary to compare moment-by-moment behavioral and neuronal activity in the freely moving animal (2,23). Note that we have not ruled out the possibility that SC lesions might cause some form of somatosensorimotor impairment. Many neurons in the SC show little or no activity during unimodal sensory stimulation but show enhanced activity in response to a somatosensory stimulus combined with a visual or auditory stimulus (19). Normal rats readily use somatosensory cues
676
BARTH
AND SCHALLERT TABLE 6
Summary of Sensorimotor Asymmetries That Follow Lesions of the Superior Colliculus (SC), Lateral Hypothalamic Region (LH), or Sensorimotor Cortex (SMC)
SC LH SMC
Head movementdependent orienting
Head movementindependent orienting
Ipsi Ipsi No bias
No bias Ipsi Ipsi
to facilitate localization of visual or auditory stimuli in space. It would be interesting to determine whether or not animals with SC damage would be able to benefit from such intermodal interactions after recovery from head movement deficits. Table 6 summarizes the sensorimotor effects of unilateral damage in the SC, SMC, and LH. Unilateral SC lesions, unlike LH or SMC lesions, did not yield a detectable sensorimotor asymmetry in the bilateral-stimulation test. However, the SC lesions caused a profound impairment of contralateral head movement that might well account for the orienting deficits reported by others who have used tests that do not distinguish sensorimotor from purely motor asymmetries. We conclude that the deep SC layers may be involved in motor control, and that any possible role in somatosensory function must be fundamentally different from that of the sensorimotor cortex or nigrostriatal systems. REFERENCES 1. BARTH, T. M., M. D. LINDNER, AND T. SCHALLERT. 1983. Sensorimotor asymmetries and tactile extinction in unilateral frontal cortex-damaged and striataI dopamine-depleted rats. Sot. Neurosci. Abstr. 9: 482. 2. BARTH, T. M., AND T. SCHALLERT. 1987. Multimodal sensorimotor function of the superior colliculus: A critical review. Submitted. 3. CHAPIN, J. K., AND C. LIN. 1984. Mapping the body representation in the Sl cortex of anesthetized and awake rats. J. Comp. Neural. 229: 199-2 13. 4. COOPER, R. M., B. H. BLAND, L. A. GILLESPIE, AND R. H. WHITAKER. 1970. Unilateral posterior cortical and unilateral collicular lesions and visually guided behavior in the rat. J. Comp. Physiol. Psycho/ 72: 286-295. 5. DUNNETT, S. B., D. M. LANE, AND P. WINN. 1985. Ibotenic acid lesions of the lateral hypothalamus: comparison with 6-hydroxydopamine-induced sensorimotor deficits. Neuroscience 14: 509-5 18. 6. EDWARDS, S. B., C. L. GINSBURGH, C. K. HENKEL, AND B. E. STEIN. 1979. Sources of subcortical projections to the superior colliculus in the cat. J. Comp. Neural. 184: 309330.
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M. A. 1983. Vision as a sensorimotor system. Pages 4 l-6 1 in T. E. ROBINSON, to Brain Research. Oxford Univ. Press, London/New York. HALL, R. D., AND E. P. LINDHOLM. 1974. Organization of motor and somatosensory neocortex in the albino rat. Brain Res. 66: 23-38. HOYMAN, L., G. D. WEESE, AND G. P. FROMMER. 1978. Tactile discrimination performance deficits following neglect-producing unilateral lateral hypothalamic lesions in the rat. Physiol. Behav. 22: 139- 147. K~RVEL, R. D., R. A. GREENFIELD, AND D. R. MEYER. 1974. Multimodal sensory neglect in rats with radical unilateral posterior isocortical and superior collicular ablations. J. Camp. Physiol. Psychol. 87: 156-162. KIRVEL, R. D. 1975. Sensorimotor responsiveness in rats with unilateral superior collicular and amygdaloid lesions. J. Comp. Physiol. Psychol. 89: 882-89 1. K~NIG, J. F. R., AND R. A. KLIPPEL. 1963. The Rat Brain: A Stereotaxic Atlas of the Forebrain and Lower Parts of the Brain Stem Williams & Wilkins, Baltimore. LIUNGBERG, T., AND U. UNGERSTEDT. 1976. Sensory inattention produced by 6-hydroxydopamine-induced degeneration of ascending dopamine neurons in the brain. Exp. NeuGOODALE,
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14. MARSHALL, J. F. 1978. Comparison ofthe sensorimotor dysfunctions produced by damage to lateral hypothalamus or superior colliculus in the rat. Exp. Neurol. 58: 203-2 17. 15. MARSHALL, J. F. 1979. Somatosensory inattention after dopamine-depleting intracerebral 6-OHDA injection: spontaneous recovery and pharmacological control. Brain Res. 117: 31 l-324. 16. MARSHALL, J. F. 1980. Basal ganglia dopaminergic control of sensorimotor functions related to motivated behavior. Pages 167-176 in R. F. THOMPSON, L. H. HICKS, AND V. B. SHVYRKOV, Eds., Neural Mechanisms of Goal-Directed Behavior and Learning. Academic Press, New York. 17. MARSHALL, J. F., N. BERRIOS,AND S. SAWYER. 1980. Neostriatal dopamine and sensory inattention. J. Comp. Physiol. Psychol. 94: 833-846. 18. MARSHALL, J. F., B. H. TURNER, AND P. TEITELBAUM. 197 1. Sensory neglect produced by lateral hypothalamic damage. Science 18: 50-60. 19. MEREDITH, M. A., AND B. E. STEIN. 1983. Interactions among converging sensory inputs in the superior colliculus. Science 221: 389-39 1. 20. MITTELMAN, G., P. J. FRAY, AND E. S. VALENSTEIN. 1985. Asymmetry in the effects of unilateral 6-OHDA lesions on eating and drinking evoked by hypothalamic stimulation. Behav.
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21. NEAFSEY, E. J., AND C. SIEVERT. 1982. A second forelimb area exists in the rat frontal cortex. Brain Res. 232: 15 1- 156. 22. PAXINOS, G., AND C. WATSON 1982. The Rat Brain in Stereotaxic Coordinates. Academic Press, New York. 23. RANCK, J. B., JR., J. L. KUBIE, S. E. Fox, S. WOLFSON, AND R. U. MULLER. 1983. Single neuron recording in behaving mammals: bridging the gap between neuronal events and sensory-behavior variables. Pages 62-93 in T. E. ROBINSON, Ed., Behavioral Approaches to Brain Research. Oxford University Press, London/New York. 24. SCHALLERT, T., T. D. HERNANDEZ, AND T. M. BARTH. 1986. Recovery of function after brain damage: severe and chronic disruption by diazepam. Brain Res. 379: 104- 111. 25. SCHALLERT, T., AND I. Q. WHISHAW. 1978. Two types of aphagia and two types of sensorimotor impairments after lateral hypothalamic lesions: observations in normal weight, dieted, and fattened rats. J. Comp. Physiol. Psychol. 92: 720-74 1. 26. SCHALLERT, T., AND I. Q. WHISHAW. 1984. Bilateral cutaneous stimulation ofthe somatosensory system in hemidecorticate rats. Behav. Neurosci. 98: 5 18-540.
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27. SCHALLERT, T., M. UPCHURCH, N. LOBAUGH, S. B. FARRAR, W. W. SPIRDUSO,P. GILLIAM, D. VAUGHN, AND R. E. WILCOX. 1982. Tactile extinction: distinguishing between sensorimotor and motor asymmetries in rats with unilateral nigrostriatal damage. Pharmacol. B&hem. Behav. 16: 455-462. 28. SCHALLERT, T., M. UPCHURCH, R. E. WILCOX, AND D. M. VAUGHN. 1983. Posture-independent sensorimotor analysis of inter-hemispheric receptor asymmetries in neostriaturn. Pharmacol. B&hem. Behav. 18: 753-759. 29. SCHNEIDER, G. E. 1967. Contrasting visuomotor functions of tectum and cortex in the golden hamster. Psychol. Forsch. 31: 52-62. 30. SCHNEIDER,G. E. 1969. Two visual systems. Brain mechanisms for localization and discrimination are disassociated by tectal and cortical lesions. Science 163: 895-902. 3 I. SPRAGUE, J. M. 1966. Interaction of cortex and superior colliculus in mediation of visually guided behavior in the cat. Science 153: 1544- 1547. 32. SPRAGUE, J. M., AND T. H. MEIKLE. 1965. The role of the superior colliculus in visuallyguided behavior. Exp. Neural. 11: 115-146. 33. STEIN, B. E. 1984. Multimodal representation in the superior colliculus and optic tectum. Pages 8 19-84 I in H. VANEGAS, Ed., Comparative Neurology of the Optic Tectum. Plenum, New York. 34. STEIN, B. E., B. MAGALHAES-CASTRO, AND L. KRUGER. 1976. Relationship between visual and tactile representations in cat superior colliculus. J. Neurophysiol. 39: 40 l-4 19. 35. WHISHAW, I. Q., T. SCHALLERT, AND B. KOLB. 198 1. An analysis offeeding and sensorimotor abilities of rats after decortication. J. Comp. Physiol. Psychol. 95: 85-103. 36. ZILLES, K. 1985. The Cortex of the Rut. Springer-Verlag, New York.