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
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
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DOI：
10.1152/jn.1994.72.2.521
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发表时间：
1994-08-01
影响因子：
2.5
通讯作者：
DELONG, MR
中科院分区：
文献类型：
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作者：
WICHMANN, T;BERGMAN, H;DELONG, MR
1.用1-methyl-4-phenyl-1，2，3，6-tetrahydropyridine.2.治疗帕金森病的非洲绿猴，研究了可逆性和不可逆性的丘脑底核神经元活动对帕金森病运动体征和苍白球内段神经元活动的影响在短臂背核内注射蝇草酚(小于或等于1微克L，1微克/微米L)可在几分钟内降低注射部位记录到的神经元活动。紧随其后的是运动迟缓、震颤和僵硬，以及对侧肢体出现运动障碍。运动效应伴随着全身行为激活，持续时间在10~60min之间，并强烈依赖于注射部位，注射到STN的外侧“臂区”首先影响对侧手臂的运动，而注射到“腿”区首先影响腿部运动。三叉神经节内注射荷包牡丹碱(小于或等于1mU L，1mUg/mU L)可轻微增加神经元活动，并诱导神经元爆发式放电。健侧肢体僵硬、动作迟钝、震颤无明显变化。两种动物(L 2亩和7亩L，L每亩10亩)注射鹅掌酸后，短链网的破坏率分别为70%和51%。与注射麝香酚类似，这会导致神经元活性降低，帕金森氏症运动体征逆转，并在对侧肢体发展为运动障碍。尽管STN损伤后震颤明显减少，但GPI中的周期性振荡神经元活动持续存在。损毁STN后，神经元振荡调制强度无明显变化。损伤STN后，GPI中表现为对扭矩施加反应的放电增加的细胞百分比显著减少。STN损毁后，随着放电频率的增加，反应的幅度和时程缩短。这些结果支持这一假说，即STN的紧张和时相活动异常增加导致GPI活性异常，是帕金森病运动体征发生的主要因素。此外，他们还暗示，基底节的细胞具有周期性爆发放电的固有特性，这在帕金森病患者的情况下是看不出来的。
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.