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Behaviorally specific limb use deficits following globus pallidus lesions in rats
341
Brain Re~eareh, 308 (1984) 341-346 Elsevicr BRE 20318
Behaviorally specific limb use deficits following globus pallidus lesions in rats J. S. S C H N E I D E R and U. E. O L A Z A B A L
Mental Retardation Res'earch Center, University of Cali~brnia at Lo~sAngeles', Los Angeles, CA 90024 and Department (~t Ps'ychologv, SUNYat Stony Brook, Stony Brook, NY 11794 (U.S.A.) (Accepted April 10th. 1984)
Key words: globus pallidus - - lesions - - m o v e m e n t - - rats
[ h e effects of bilateral globus pallidus lesions were observed in rats trained to perform a somatosensory/proprioceptive guided foreLimb reaching task. Postlesion reaching became very inaccurate, characterized by gross abnormalities in limb and body posture. Posrural abnormalities and paw use deficits were not observed in other situations. These results suggest that pallidal damagc does n o / r e sult in a simple motor deficit but interferes with motor performance when m o v e m e n t s depend upon somesthetic and proprioceptive feedback
The basal ganglia (BG) have long been thought to play an important role in the modulation of limb movements. Data from single unit recording as well as lesion studies have supported this contention. However, the precise mechanisms by which the BG influence limb, or any other movements, remain virtually unknown. Considering the present state of knowledge concerning BG anatomy and physiology, it is unlikely that the BG are directly involved in generating distal limb movements per se 3. That is, BG influences on motoneurons are quite indirect. More probably, the BG are involved in complex integrations of sensory signals with underlying motor patterns. Recently, it has been suggested that deficits in distal limb movements in primates resulting from disruption of pallidal outputs are not due to a motor impairment per se, but are more complex in nature s. Monkeys were trained to perform self-paced limb movements without the use of visual feedback. Subsequent pallidal cooling resulted in a breakdown in task performance which was overcome by allowing the animals use of visual feedback. These results, as well as others with Parkinson's disease patients'), indicate the complex nature of the role of the BG in movement.
Previous studies in rodents examining the effects
of BG damage on limb movement have noted little gross motor impairment. Globus pallidus-lesioned rats, though, showed a cessation of bar-pressing behavior with the limb contralateral to the lesion. These deficits were interpreted as a loss of the capacity to use the affected limb in performance of learned, organized movements s. This type of examination of motor function is quite gross and may not be appropriate to reveal the true nature of the motor impairment following pallidal damage. In the present experiment, paw reaching and digit usage were used to study the effects of globus pallidus damage on the motor system. In this regard, simultaneous high-speed film analysis of limb and posrural movements was utilized. Paw reaching in the rat, at the most basic level, combines somatosensory and proprioceptive information from the forelimb with central motor information to coordinate discrete forelimb movements with gross postural adjustments m. It is possible that the contribution of the BG to these movements is to integrate sensory information with distal and proximal motor signals leading to the elaboration of reaching movements rather than directly mediating forelimb and digit movements. Intact male and female Lashley rats weighing 250-300 g (n = 10) were trained to reach at various
Correspondence: J. S. Schncider, Mental Retardation Research Center, University of California at Los Angeles, 760 Westwood Plaza, Room 58-258, Los Angeles, C A 90024, U.S.A. 0006-8993/84/$03.0(~ © 1984 Elsex ier Science Publishers B.V,
342 depths into a narrow, 1-cm diameter tube, with their preferred forepaw, to obtain a small food pellet (50
opaque wall of a Plexiglass tesiing chamber, eliminating the animal's use of visual cues and making the
mg). The tube was attached from the outside to an
reaching response dependent primarily upon soma-
A.
movie comera
ie ,+,J m e r a
plunge~
tube pellei
B.
C.
) Fig. 1. A: This illustration depicts a rat in the experimental apparatus. Super 8 mm movie cameras were positioned as shown to record body movements and movements of the limb in the tube. B and C: the extents of globus pallidus (B) and control (C) lesions.
343 tosensory and proprioceptive information (Fig. 1A). Rats were housed individually and maintained at 80% body weight. Preoperatively, animals were first allowed to grab pellets placed close to the opening of the tube. Pellets were gradually moved farther away from the tube opening until animals were able to accurately obtain pellets more than 2 cm into the tube. A moveable piston placed in the tube positioned food pellets 2.0-25 mm from the opening of the tube and thus determined the length of the paw reach. During training sessions, approximately 50-75 pellets were given per day. Training continued until the animals could reach pellets placed 25 mm from the opening of the tube. During data acquisition, animals were given 10 trials at each of 3 positions (line 3 on the tube (10 ram), line 4 (15 ram), and line 5 (20 ram)). Body posture and limb movement were photographed simultaneously (super 8 mm movie film at 36 frames/s) several times prior to lesioning. Data were analyzed in terms of accuracy in obtaining the food pellet (i.e. mean number of successful reaches, mean number of unsuccessful reaches) and posture of the limb and body. A successful paw reach was one which resulted in the animal grabbing a pellet and removing it from the tube. An unsuccessful paw reach was when the animal either touched the pellet but did not grab it and remove it from the tube or when the paw reach was too short to reach the pellet. During the 10 testing trials, although the rat was allowed to continue reaching for the pellet after an unsuccessful reach until the pellet was obtained, only the first unsuccessful reach in the sequence was counted. On other trials, the accuracy of paw reaching was assessed by counting the number of reaches required for obtaining one pellet. After preoperative testing, bilateral globus pallidus (GP) lesions were produced in 6 rats (2 m A DC current for 10 s) and control lesions of the ventromedial motor thalamus and/or internal capsule were produced in 4 rats (similar parameters) (Fig. 1B, C). All animals served as their own controls. Normal rats easily reached and obtained food pellets placed 10-20 mm into the tube. These movements were very accurate as noted by the high number of successful reaches vs the low number of unsuccessful reaches (Fig. 2). However, normal rats did show a decrease in performance accuracy as they were required to reach deeper into the tube (e.g. J~ successful reaches at line 3 = 8.9 + 0.1, X successful
PRE GP LESION Line 5
Line 4
POST GP LESION Li ne 5
Line 5
Line 4
10-
a_
z
Line 5
,,...T..-
6-
•
vCz S
U
S
U
S
U
U
S
U
S
U
Fig. 2. The mean number of successful (S) and unsuccessful (U) paw reaches for all rats before and after bilateral GP lesions. Paw reaching becomes very inaccurate following lesioning. reaches at line 5 = 3.6 _+ 0.3). At lines 3 and 4, rats were usually capable of obtaining the pellet on the first reach attempt. In intact animals, the limb characteristically entered the tube with the palm of the paw facing down, digits extended or cupped (Fig. 3A). Normal paw reaching was similar to that previously described by others 12. Body posture during normal paw reaching consisted primarily of a straight-on approach to the tube or a slight curvature of the body with the head facing the tube opening (Fig. 3B). Following lesioning, animals displayed the aphagia, adipsia and weight loss characteristic of pallidallesioned animals. Pallidal rats initially ceased to perform the reaching task. Approximately 2 - 4 weeks of retraining was undertaken before testing and filming resumed. Bilateral GP lesions caused obvious disruptions in reaching behavior in rats tested up to 8 weeks following lesioning. Typically, GP-lesioned rats were very inaccurate in their reaching responses and were often unable to grab food pellets placed within a few millimeters of the tube opening (Fig. 3B). The differences in pre- and postlesion reaching responses at each tube line were statistically significant (t-test, P < 0.001). The inaccuracy of the reaching movements became more pronounced the further the pellets were positioned from the tube opening (Fig. 2). Also, at lines 3 and 4, the number of reaching attempts to secure the pellet increased. Normal rats required on average 1.1 +_ 0.2, 1.8 _+ 0.7, and 3.2 + 1.4 paw reaches to obtain one pellet at lines 3, 4, and 5, respectively. Following bilateral GP lesions, rats required on average 5.6 _+ 2.7, 7.3 + 3.0, and 1> 10.0
344
PAW REACH AND BODY POSTURE
Limb
A. NORMAL
Body
Limb
B. POST GP LESIONS
Body
Fig. 3. A: photographs of normal paw and body posture. The paw enters the tube with a palm-down posture with digits extended. Normal rats approach the tube straight on and maintain a stable posture during reaching. B: photographs of paw and body posture following GP lesions. The paw now enters the tube with a palm-sideways or palm-up posture. Lesioned rats severely twist their bodies and almost invert themselves during paw reaching. These rats seem unable to maintain a stable body posture to enable completion of paw reaching.
345 (no successful reaches) paw reaches to obtain one pellet at lines 3, 4, and 5, respectively. The topography of the reaching movement also changed after GP lesions. Postlesion reaching was characterized by a palm-sideways or palm-up posture with the digits spread and extended (Fig. 3B) as opposed to the normal palm-down, cupped digit posture. This postural change obviously contributed to the difficulties these animals had in grabbing pellets and removing them from the tube. Photos in Fig. 3 all depict the position of the paw during the extension phase of the movement. Following bilateral GP lesions, rats often adopted a brushing or batting motion of the forelimb during reaching attempts. This resulted in the food pellet being batted around until it fell out of the tube, at which time the rat would grab it and eat it. Globus pallidus-lesioned animals also showed severe abnormalities in body posture. This posture consisted of a sideways approach to the tube accompanied by an exaggerated head tilt and body curvature (Fig. 3B). While limb and body movements were observed to be quite disordered in the context of the paw reach paradigm, similar movements were not impaired under other circumstances. Lesioned rats, when placed in an open field, displayed no gross limb or digit movement deficits, or postural abnormalities. When observed in their home cages, lesioned animals had no difficulties in picking up, manipulating, and eating food pellets similar to those used in the testing situation, when they were visible and easily obtainable from a dish on the floor of the cage. Filmed analysis of these movement sequences were indistinguishable from films obtained from the same animals prior to lesioning. At the completion of the experiment, animals were overdosed with barbiturate and perfused with 10% formol-saline. Brains were removed, sectioned, and stained with cresyl violet. All lesions in animals in the GP group involved at least 51)c/c of the globus pallidus with little intrusion into surrounding structures. Lesions in thalamic animals included the ventromedial, ventro-anterior and ventro-lateral nuclei. Other animals received lesions medial to the GP in the reticular nucleus of the thalamus and the internal capsule without impinging upon the GP. None of these lesions resulted in feeding, paw reaching, or postural deficits similar to those observed in GP-lesioned animals. These animals showed slight but statistically in-
significant reductions in paw reach accuracy. Most of these animals had problems with actually grabbing the pellet and holding on to it. These data indicate that disruptions of paw reaching behavior following GP damage are not simply due to a generalized forelimb motor deficit. Rather. basal ganglia damage seems to interfere with the performance of organized limb movements whose successful execution is dependent upon somesthetic and proprioceptive feedback. These results are consistent with previous findings which suggested that impairment in reaching behavior due to pharmacological lesions of the substantia nigra or caudate nucleus was not due to paralysis of the limb or paw but to some loss of integrative control of the limb Is. It is possible that some of the deficits seen following GP damage may be attributable to damage to descending frontal cortical fiber systems ~'. However, we feel that this probably did not contribute significantly to the present results. In this experiment, lesions through several levels of the internal capsule (which carries the descending frontal fiber system) and through the motor thalamus (which projects to the frontal cortical area) did not result in reaching and postural deficits resembling those seen following GP damage. It has been described, though, that frontal cortex-lesioned rats have problems performing discrete digit use tasks~ with no observed postural deficits. Even if some disruption of descending cortical fibers contributed to some of the presently observed digit use deficits, it cannot account for the gross postural abnormalities of the limb or body presently observed. Furthermore, the idea that the presently observed impairments in paw reaching are due to interference with basal ganglia function is supported by experiments showing disruption of paw reaching with single pulse stimulation of the caudate nucleus preceding the movement 11or coinciding with reach onseta. The present findings are in agreement with results of a recently published report concerning the role of the BG in oro-ingestive and postural motor mechanisms. Bilateral GP-lesioned rats had great difficulty in licking at a recessed drinking spout, characterized by an inability to correctly position the head for drinking and a failure to achieve postural fixation of the head 7. In addition, when changes in the drinking tube's position required the animal to readjust the position of its body, postural difficulties inw~lving
346 both head and trunk musculature were apparent. These results, as well as those of the present experiment, underscore the i m p o r t a n c e of the basal ganglia when the somatosensory/propriocePtive modalities are used to influence m o v e m e n t . In both experimental situations, animals had to perform integrated m o v e m e n t s solely on the basis of s o m a t o s e n s o r y and proprioceptive signals. In both cases, animals had severe p r o b l e m s performing these movements. In the present e x p e r i m e n t , animals showed no deficits in limb use or postural stability in open field or in grabbing easily o b t a i n a b l e , visible food pellets. Lastly, single units r e c o r d e d in the m o t o r cortex contralateral to the reaching forepaw in rats trained to p e r f o r m a task similar to the one presently described, were maximally activated i m m e d i a t e l y before and during the actual grabbing of the food pellet (digit use) 2. In contrast, units r e c o r d e d in the caudate nucleus contralateral to the responding f o r e p a w showed maximal activation both preceding and fol-
lowing the grabbing of the pellet. C a u d a t e units did not a p p e a r to be phasically related to limb or digit movements 2. On the basis of these findings, it was suggested that the caudate may be involved m controlling postural reactions which would stabilize the body in front of the feeding lubc in a position necessary for successful reaching, whereas the m o t o r cortex may be more involved in discrete digit use-'. This idea is s u p p o r t e d by the results r e p o r t e d in this paper. While the precise role o~ the BG m the control of m o v e m e n t is still in question, i! is suggested that at least part of the B G ' s influence over the m o t o r system entails the B G ' s processing and lransmission (i.e. gating) of behaviorally relevant sensory signals and an integration of this function with systems (i.e. postural) which support movemcnt~
1 Castro, A. J., The effects of cortical ablations on digital usage in the rat, Brain Research, 37 (1972) 173-185. 2 Dolbakyan, E., Hernandez-Mesa, N. and Bures, J., Skilled forelimb movements and unit activity in motor cortex and caudate nucleus in rats, Neuroscience, 2 (1977) 73-80. 3 Dray, A., The physiology and pharmacology of the mammalian basal ganglia, Progr. Neurobiol., 14 (1980) 221-235. 4 Hernandez-Mesa, N. and Bures, J., Impairment of lateralized reaching by movement-synchronized stimulation of motor centers in rats, Exp. Neurol., 57 (1977) 67-80. 5 Hore, J., Meyer-Lohman, J. and Brooks, V. B., Basal ganglia cooling disables learned arm movements of monkeys in the absence of visual guidance, Science, 195 (1977) 584-586. 6 Knook, H. L., The Fibre-Connections of the Forebrain, Royal Van Gorcum, Assen, The Netherlands, 1965. 7 Labuszewski, T., Lockwood. R., McManus, F. E., Edelstein, L. R. and Lidsky, T. I., The role of postural deficits in oro-ingestive problems caused by globus pallidus lesions, Exp. Neurol., 74 ( 1981) 93-110.
8 Levine, M. S., Ferguson, N., Krcmick. C J., Gustafson..t. W. and Schwartzbaum, J. S.. Scnsorimotor dysfunctions and aphagia and adipsia following pallidal lesions in rats. J. comp. physiol. Psychol., 77 (1971) 282-293. 9 Martin, J. P., The Basal Ganglia and Posture, Lippincott. Philadelphia, 1967. 10 Megirian, D., Buresova, O.. Bures. J. and Dimond, S., Electrophysiological correlates of discrete forelimb movements in rats, Electroenceph. olin. Neurophysiol., 36 (1974) 131-139. 11 Moroz. V. M. and Bures, J., Caudate stimulation prolongs latency of acoustically and visually signalled reaching in rats, Brain Research, 259 (1983) 298-30l). 12 Moroz, V. M. and Bures, J.. A telerecording analysis of reaching disruptions in rats after stimulation or lesion, Physiol. Behav., 31 (1983) 255-257. 13 Siegfried, B. and Bures, J., Handedness in rats: blockade of reaching behavior by unilateral t'~-OHDA injections into substantia nigra and caudate nucleus, Phvsioll Psychot., 8 (1980) 360-368.
The authors thank Harriet Laird and Diane CaoloSchneider for technical assistance. This research was s u p p o r t e d by N I N C D S G r a n t 16054.
Brain Re~eareh, 308 (1984) 341-346 Elsevicr BRE 20318
Behaviorally specific limb use deficits following globus pallidus lesions in rats J. S. S C H N E I D E R and U. E. O L A Z A B A L
Mental Retardation Res'earch Center, University of Cali~brnia at Lo~sAngeles', Los Angeles, CA 90024 and Department (~t Ps'ychologv, SUNYat Stony Brook, Stony Brook, NY 11794 (U.S.A.) (Accepted April 10th. 1984)
Key words: globus pallidus - - lesions - - m o v e m e n t - - rats
[ h e effects of bilateral globus pallidus lesions were observed in rats trained to perform a somatosensory/proprioceptive guided foreLimb reaching task. Postlesion reaching became very inaccurate, characterized by gross abnormalities in limb and body posture. Posrural abnormalities and paw use deficits were not observed in other situations. These results suggest that pallidal damagc does n o / r e sult in a simple motor deficit but interferes with motor performance when m o v e m e n t s depend upon somesthetic and proprioceptive feedback
The basal ganglia (BG) have long been thought to play an important role in the modulation of limb movements. Data from single unit recording as well as lesion studies have supported this contention. However, the precise mechanisms by which the BG influence limb, or any other movements, remain virtually unknown. Considering the present state of knowledge concerning BG anatomy and physiology, it is unlikely that the BG are directly involved in generating distal limb movements per se 3. That is, BG influences on motoneurons are quite indirect. More probably, the BG are involved in complex integrations of sensory signals with underlying motor patterns. Recently, it has been suggested that deficits in distal limb movements in primates resulting from disruption of pallidal outputs are not due to a motor impairment per se, but are more complex in nature s. Monkeys were trained to perform self-paced limb movements without the use of visual feedback. Subsequent pallidal cooling resulted in a breakdown in task performance which was overcome by allowing the animals use of visual feedback. These results, as well as others with Parkinson's disease patients'), indicate the complex nature of the role of the BG in movement.
Previous studies in rodents examining the effects
of BG damage on limb movement have noted little gross motor impairment. Globus pallidus-lesioned rats, though, showed a cessation of bar-pressing behavior with the limb contralateral to the lesion. These deficits were interpreted as a loss of the capacity to use the affected limb in performance of learned, organized movements s. This type of examination of motor function is quite gross and may not be appropriate to reveal the true nature of the motor impairment following pallidal damage. In the present experiment, paw reaching and digit usage were used to study the effects of globus pallidus damage on the motor system. In this regard, simultaneous high-speed film analysis of limb and posrural movements was utilized. Paw reaching in the rat, at the most basic level, combines somatosensory and proprioceptive information from the forelimb with central motor information to coordinate discrete forelimb movements with gross postural adjustments m. It is possible that the contribution of the BG to these movements is to integrate sensory information with distal and proximal motor signals leading to the elaboration of reaching movements rather than directly mediating forelimb and digit movements. Intact male and female Lashley rats weighing 250-300 g (n = 10) were trained to reach at various
Correspondence: J. S. Schncider, Mental Retardation Research Center, University of California at Los Angeles, 760 Westwood Plaza, Room 58-258, Los Angeles, C A 90024, U.S.A. 0006-8993/84/$03.0(~ © 1984 Elsex ier Science Publishers B.V,
342 depths into a narrow, 1-cm diameter tube, with their preferred forepaw, to obtain a small food pellet (50
opaque wall of a Plexiglass tesiing chamber, eliminating the animal's use of visual cues and making the
mg). The tube was attached from the outside to an
reaching response dependent primarily upon soma-
A.
movie comera
ie ,+,J m e r a
plunge~
tube pellei
B.
C.
) Fig. 1. A: This illustration depicts a rat in the experimental apparatus. Super 8 mm movie cameras were positioned as shown to record body movements and movements of the limb in the tube. B and C: the extents of globus pallidus (B) and control (C) lesions.
343 tosensory and proprioceptive information (Fig. 1A). Rats were housed individually and maintained at 80% body weight. Preoperatively, animals were first allowed to grab pellets placed close to the opening of the tube. Pellets were gradually moved farther away from the tube opening until animals were able to accurately obtain pellets more than 2 cm into the tube. A moveable piston placed in the tube positioned food pellets 2.0-25 mm from the opening of the tube and thus determined the length of the paw reach. During training sessions, approximately 50-75 pellets were given per day. Training continued until the animals could reach pellets placed 25 mm from the opening of the tube. During data acquisition, animals were given 10 trials at each of 3 positions (line 3 on the tube (10 ram), line 4 (15 ram), and line 5 (20 ram)). Body posture and limb movement were photographed simultaneously (super 8 mm movie film at 36 frames/s) several times prior to lesioning. Data were analyzed in terms of accuracy in obtaining the food pellet (i.e. mean number of successful reaches, mean number of unsuccessful reaches) and posture of the limb and body. A successful paw reach was one which resulted in the animal grabbing a pellet and removing it from the tube. An unsuccessful paw reach was when the animal either touched the pellet but did not grab it and remove it from the tube or when the paw reach was too short to reach the pellet. During the 10 testing trials, although the rat was allowed to continue reaching for the pellet after an unsuccessful reach until the pellet was obtained, only the first unsuccessful reach in the sequence was counted. On other trials, the accuracy of paw reaching was assessed by counting the number of reaches required for obtaining one pellet. After preoperative testing, bilateral globus pallidus (GP) lesions were produced in 6 rats (2 m A DC current for 10 s) and control lesions of the ventromedial motor thalamus and/or internal capsule were produced in 4 rats (similar parameters) (Fig. 1B, C). All animals served as their own controls. Normal rats easily reached and obtained food pellets placed 10-20 mm into the tube. These movements were very accurate as noted by the high number of successful reaches vs the low number of unsuccessful reaches (Fig. 2). However, normal rats did show a decrease in performance accuracy as they were required to reach deeper into the tube (e.g. J~ successful reaches at line 3 = 8.9 + 0.1, X successful
PRE GP LESION Line 5
Line 4
POST GP LESION Li ne 5
Line 5
Line 4
10-
a_
z
Line 5
,,...T..-
6-
•
vCz S
U
S
U
S
U
U
S
U
S
U
Fig. 2. The mean number of successful (S) and unsuccessful (U) paw reaches for all rats before and after bilateral GP lesions. Paw reaching becomes very inaccurate following lesioning. reaches at line 5 = 3.6 _+ 0.3). At lines 3 and 4, rats were usually capable of obtaining the pellet on the first reach attempt. In intact animals, the limb characteristically entered the tube with the palm of the paw facing down, digits extended or cupped (Fig. 3A). Normal paw reaching was similar to that previously described by others 12. Body posture during normal paw reaching consisted primarily of a straight-on approach to the tube or a slight curvature of the body with the head facing the tube opening (Fig. 3B). Following lesioning, animals displayed the aphagia, adipsia and weight loss characteristic of pallidallesioned animals. Pallidal rats initially ceased to perform the reaching task. Approximately 2 - 4 weeks of retraining was undertaken before testing and filming resumed. Bilateral GP lesions caused obvious disruptions in reaching behavior in rats tested up to 8 weeks following lesioning. Typically, GP-lesioned rats were very inaccurate in their reaching responses and were often unable to grab food pellets placed within a few millimeters of the tube opening (Fig. 3B). The differences in pre- and postlesion reaching responses at each tube line were statistically significant (t-test, P < 0.001). The inaccuracy of the reaching movements became more pronounced the further the pellets were positioned from the tube opening (Fig. 2). Also, at lines 3 and 4, the number of reaching attempts to secure the pellet increased. Normal rats required on average 1.1 +_ 0.2, 1.8 _+ 0.7, and 3.2 + 1.4 paw reaches to obtain one pellet at lines 3, 4, and 5, respectively. Following bilateral GP lesions, rats required on average 5.6 _+ 2.7, 7.3 + 3.0, and 1> 10.0
344
PAW REACH AND BODY POSTURE
Limb
A. NORMAL
Body
Limb
B. POST GP LESIONS
Body
Fig. 3. A: photographs of normal paw and body posture. The paw enters the tube with a palm-down posture with digits extended. Normal rats approach the tube straight on and maintain a stable posture during reaching. B: photographs of paw and body posture following GP lesions. The paw now enters the tube with a palm-sideways or palm-up posture. Lesioned rats severely twist their bodies and almost invert themselves during paw reaching. These rats seem unable to maintain a stable body posture to enable completion of paw reaching.
345 (no successful reaches) paw reaches to obtain one pellet at lines 3, 4, and 5, respectively. The topography of the reaching movement also changed after GP lesions. Postlesion reaching was characterized by a palm-sideways or palm-up posture with the digits spread and extended (Fig. 3B) as opposed to the normal palm-down, cupped digit posture. This postural change obviously contributed to the difficulties these animals had in grabbing pellets and removing them from the tube. Photos in Fig. 3 all depict the position of the paw during the extension phase of the movement. Following bilateral GP lesions, rats often adopted a brushing or batting motion of the forelimb during reaching attempts. This resulted in the food pellet being batted around until it fell out of the tube, at which time the rat would grab it and eat it. Globus pallidus-lesioned animals also showed severe abnormalities in body posture. This posture consisted of a sideways approach to the tube accompanied by an exaggerated head tilt and body curvature (Fig. 3B). While limb and body movements were observed to be quite disordered in the context of the paw reach paradigm, similar movements were not impaired under other circumstances. Lesioned rats, when placed in an open field, displayed no gross limb or digit movement deficits, or postural abnormalities. When observed in their home cages, lesioned animals had no difficulties in picking up, manipulating, and eating food pellets similar to those used in the testing situation, when they were visible and easily obtainable from a dish on the floor of the cage. Filmed analysis of these movement sequences were indistinguishable from films obtained from the same animals prior to lesioning. At the completion of the experiment, animals were overdosed with barbiturate and perfused with 10% formol-saline. Brains were removed, sectioned, and stained with cresyl violet. All lesions in animals in the GP group involved at least 51)c/c of the globus pallidus with little intrusion into surrounding structures. Lesions in thalamic animals included the ventromedial, ventro-anterior and ventro-lateral nuclei. Other animals received lesions medial to the GP in the reticular nucleus of the thalamus and the internal capsule without impinging upon the GP. None of these lesions resulted in feeding, paw reaching, or postural deficits similar to those observed in GP-lesioned animals. These animals showed slight but statistically in-
significant reductions in paw reach accuracy. Most of these animals had problems with actually grabbing the pellet and holding on to it. These data indicate that disruptions of paw reaching behavior following GP damage are not simply due to a generalized forelimb motor deficit. Rather. basal ganglia damage seems to interfere with the performance of organized limb movements whose successful execution is dependent upon somesthetic and proprioceptive feedback. These results are consistent with previous findings which suggested that impairment in reaching behavior due to pharmacological lesions of the substantia nigra or caudate nucleus was not due to paralysis of the limb or paw but to some loss of integrative control of the limb Is. It is possible that some of the deficits seen following GP damage may be attributable to damage to descending frontal cortical fiber systems ~'. However, we feel that this probably did not contribute significantly to the present results. In this experiment, lesions through several levels of the internal capsule (which carries the descending frontal fiber system) and through the motor thalamus (which projects to the frontal cortical area) did not result in reaching and postural deficits resembling those seen following GP damage. It has been described, though, that frontal cortex-lesioned rats have problems performing discrete digit use tasks~ with no observed postural deficits. Even if some disruption of descending cortical fibers contributed to some of the presently observed digit use deficits, it cannot account for the gross postural abnormalities of the limb or body presently observed. Furthermore, the idea that the presently observed impairments in paw reaching are due to interference with basal ganglia function is supported by experiments showing disruption of paw reaching with single pulse stimulation of the caudate nucleus preceding the movement 11or coinciding with reach onseta. The present findings are in agreement with results of a recently published report concerning the role of the BG in oro-ingestive and postural motor mechanisms. Bilateral GP-lesioned rats had great difficulty in licking at a recessed drinking spout, characterized by an inability to correctly position the head for drinking and a failure to achieve postural fixation of the head 7. In addition, when changes in the drinking tube's position required the animal to readjust the position of its body, postural difficulties inw~lving
346 both head and trunk musculature were apparent. These results, as well as those of the present experiment, underscore the i m p o r t a n c e of the basal ganglia when the somatosensory/propriocePtive modalities are used to influence m o v e m e n t . In both experimental situations, animals had to perform integrated m o v e m e n t s solely on the basis of s o m a t o s e n s o r y and proprioceptive signals. In both cases, animals had severe p r o b l e m s performing these movements. In the present e x p e r i m e n t , animals showed no deficits in limb use or postural stability in open field or in grabbing easily o b t a i n a b l e , visible food pellets. Lastly, single units r e c o r d e d in the m o t o r cortex contralateral to the reaching forepaw in rats trained to p e r f o r m a task similar to the one presently described, were maximally activated i m m e d i a t e l y before and during the actual grabbing of the food pellet (digit use) 2. In contrast, units r e c o r d e d in the caudate nucleus contralateral to the responding f o r e p a w showed maximal activation both preceding and fol-
lowing the grabbing of the pellet. C a u d a t e units did not a p p e a r to be phasically related to limb or digit movements 2. On the basis of these findings, it was suggested that the caudate may be involved m controlling postural reactions which would stabilize the body in front of the feeding lubc in a position necessary for successful reaching, whereas the m o t o r cortex may be more involved in discrete digit use-'. This idea is s u p p o r t e d by the results r e p o r t e d in this paper. While the precise role o~ the BG m the control of m o v e m e n t is still in question, i! is suggested that at least part of the B G ' s influence over the m o t o r system entails the B G ' s processing and lransmission (i.e. gating) of behaviorally relevant sensory signals and an integration of this function with systems (i.e. postural) which support movemcnt~
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The authors thank Harriet Laird and Diane CaoloSchneider for technical assistance. This research was s u p p o r t e d by N I N C D S G r a n t 16054.