THE PRIMATE SUBTHALAMIC NUCLEUS .3. CHANGES IN MOTOR BEHAVIOR AND NEURONAL-ACTIVITY IN THE INTERNAL PALLIDUM INDUCED BY SUBTHALAMIC INACTIVATION IN THE MPTP MODEL OF PARKINSONISM

被引:324
作者
WICHMANN, T
BERGMAN, H
DELONG, MR
机构
[1] HEBREW UNIV JERUSALEM, HADASSAH MED SCH, DEPT PHYSIOL, IL-91010 JERUSALEM, ISRAEL
[2] EMORY UNIV, DEPT NEUROL, ATLANTA, GA 30322 USA
关键词
D O I
10.1152/jn.1994.72.2.521
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
1. The effects of reversible and irreversible pharmacological manipulations of the neuronal activity in the subthalamic nucleus (STN) on parkinsonian motor signs and neuronal activity in the internal segment of the globus pallidus (GPi) were studied in African green monkeys rendered parkinsonian by treatment with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. 2. Muscimol injections (less than or equal to 1 mu l, 1 mu g/mu l) into STN reduced neuronal activity recorded at the injection site within minutes. This was immediately followed by reduced akinesia, tremor, and rigidity, as well as the emergence of dyskinesias in contralateral limbs. The motor effects were accompanied by generalized behavioral activation, lasted between 10 and 60 min, and were strongly dependent on the site of injection, with injections into the lateral ''arm area'' of STN first affecting contralateral arm movements and injections into the ''leg'' area affecting leg movements first. 3. Bicuculline injections (less than or equal to 1 mu l, 1 mu g/mu l) into STN marginally increased the neuronal activity and induced neuronal discharge in bursts. Rigidity, akinesia, and tremor in the contralateral limbs were not changed. 4. Injections of ibotenic acid in two animals (2 and 7 mu l, 10 mu g/mu l) resulted in 70 and 51% destruction of STN, respectively. Similarly to the muscimol injections, this resulted in a reduction of the neuronal activity, a reversal of parkinsonian motor signs, and the development of dyskinesias in the contralateral limbs. 5. Although tremor was significantly reduced after STN lesions, periodic oscillatory neuronal activity in GPi persisted. The strength of modulation of the neuronal oscillation was not significantly changed after STN lesion. 6. The percentage of cells in GPi exhibiting increases in discharge in response to torque application was significantly reduced after STN lesion. The magnitude and duration of the responses with increase in firing rate were reduced after STN lesioning. 7. These results support the hypothesis that abnormally increased tonic and phasic activity in STN leads to abnormal GPi activity and is a major factor in the development of parkinsonian motor signs. Furthermore they imply that cells in the basal ganglia have the intrinsic property of discharging in periodic bursts, which is unmasked under parkinsonian conditions.
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页码:521 / 530
页数:10
相关论文
共 50 条
[1]  
ALEXANDER GE, 1990, PROG BRAIN RES, V85, P119
[2]   PARALLEL ORGANIZATION OF FUNCTIONALLY SEGREGATED CIRCUITS LINKING BASAL GANGLIA AND CORTEX [J].
ALEXANDER, GE ;
DELONG, MR ;
STRICK, PL .
ANNUAL REVIEW OF NEUROSCIENCE, 1986, 9 :357-381
[3]  
[Anonymous], 1987, BASAL GANGLIA 2
[4]   SUBTHALAMIC NUCLEOTOMY ALLEVIATES PARKINSONISM IN THE 1-METHYL-4-PHENYL-1,2,3,6-TETRAHYDROPYRIDINE (MPTP)-EXPOSED PRIMATE [J].
AZIZ, TZ ;
PEGGS, D ;
AGARWAL, E ;
SAMBROOK, MA ;
CROSSMAN, AR .
BRITISH JOURNAL OF NEUROSURGERY, 1992, 6 (06) :575-582
[5]   LESION OF THE SUBTHALAMIC NUCLEUS FOR THE ALLEVIATION OF 1-METHYL-4-PHENYL-1,2,3,6-TETRAHYDROPYRIDINE (MPTP)-INDUCED PARKINSONISM IN THE PRIMATE [J].
AZIZ, TZ ;
PEGGS, D ;
SAMBROOK, MA ;
CROSSMAN, AR .
MOVEMENT DISORDERS, 1991, 6 (04) :288-292
[6]  
Baron M., 1993, Society for Neuroscience Abstracts, V19, P1584
[7]  
Baron M. S., 1992, Society for Neuroscience Abstracts, V18, P693
[8]  
BENABID AL, 1993, SOC NEUR ABSTR, V19, P1052
[9]   REVERSAL OF RIGIDITY AND IMPROVEMENT IN MOTOR-PERFORMANCE BY SUBTHALAMIC HIGH-FREQUENCY STIMULATION IN MPTP-TREATED MONKEYS [J].
BENAZZOUZ, A ;
GROSS, C ;
FEGER, J ;
BORAUD, T ;
BIOULAC, B .
EUROPEAN JOURNAL OF NEUROSCIENCE, 1993, 5 (04) :382-389
[10]   THE PRIMATE SUBTHALAMIC NUCLEUS .2. NEURONAL-ACTIVITY IN THE MPTP MODEL OF PARKINSONISM [J].
BERGMAN, H ;
WICHMANN, T ;
KARMON, B ;
DELONG, MR .
JOURNAL OF NEUROPHYSIOLOGY, 1994, 72 (02) :507-520