Takakusaki K, Habaguchi T, Ohtinata-Sugimoto J, Saitoh K, Sakamoto T
Department of Physiology, College of Medicine, Asahikawa Medical College, Midorigaoka-Higashi 2-1, Asahikawa 078-8510, Japan.
Neuroscience. 2003;119(1):293-308. doi: 10.1016/s0306-4522(03)00095-2.
The present study is designed to elucidate how basal ganglia afferents from the substantia nigra pars reticulata (SNr) to the mesopontine tegmental area of the brainstem contribute to gait control and muscle-tone regulation. We used unanesthetized and acutely decerebrated cats (n=27) in which the striatum, thalamus and cerebral cortex were removed but the SNr was preserved. Repetitive stimulation (50 Hz, 10-60 microA, for 5-20 s) applied to a mesencephalic locomotor region (MLR), which corresponded to the cuneiform nucleus, and adjacent areas, evoked locomotor movements. On the other hand, stimulation of a muscle-tone inhibitory region in the pedunculopontine tegmental nucleus (PPN) suppressed postural muscle tone. An injection of either glutamatergic agonists (N-methyl-D-aspartic acid and kainic acid) or GABA antagonists (bicuculline and picrotoxin) into the MLR and PPN also induced locomotion and muscle-tone suppression, respectively. Repetitive electrical stimuli (50-100 Hz, 20-60 microA for 5-20 s) delivered to the SNr alone did not alter muscular activity. However stimulating the lateral part of the SNr attenuated and blocked PPN-induced muscle-tone suppression. Moreover, weaker stimulation of the medial part of the SNr reduced the number of step cycles and disturbed the rhythmic alternation of limb movements of MLR-induced locomotion. The onset of locomotion was delayed as the stimulus intensity was increased. At a higher strength SNr stimulation abolished the locomotion. An injection of bicuculline into either the PPN or the MLR diminished the SNr effects noted above. These results suggest that locomotion and postural muscle tone are subject to modulation by GABAergic nigrotegmental projections which have a partial functional topography: a lateral and medial SNr, for regulation of postural muscle tone and locomotion, respectively. We conclude that disorders of the basal ganglia may include dysfunction of the nigrotegmental (basal ganglia-brainstem) systems, which consequently leads to the production of abnormal muscle tone and gait disturbance.
本研究旨在阐明黑质网状部（SNr）至脑干中脑桥被盖区的基底神经节传入纤维如何对步态控制和肌张力调节产生影响。我们使用了未麻醉且急性去大脑的猫（n = 27），这些猫的纹状体、丘脑和大脑皮层已被切除，但保留了SNr。对对应于楔状核的中脑运动区（MLR）及其相邻区域施加重复刺激（50 Hz，10 - 60 μA，持续5 - 20 s）可诱发运动。另一方面，刺激脚桥被盖核（PPN）中的肌张力抑制区可抑制姿势肌张力。向MLR和PPN注射谷氨酸能激动剂（N - 甲基 - D - 天冬氨酸和 kainic 酸）或GABA拮抗剂（荷包牡丹碱和印防己毒素）也分别诱导了运动和肌张力抑制。单独向SNr施加重复电刺激（50 - 100 Hz，20 - 60 μA，持续5 - 20 s）并不会改变肌肉活动。然而，刺激SNr的外侧部分可减弱并阻断PPN诱导产生的肌张力抑制。此外，对SNr内侧部分进行较弱刺激会减少步周期数量，并干扰MLR诱导运动中肢体运动的节律性交替。随着刺激强度增加，运动起始延迟。在更高强度下，SNr刺激会使运动消失。向PPN或MLR注射荷包牡丹碱会减弱上述SNr的作用。这些结果表明，运动和姿势肌张力受到具有部分功能拓扑结构的GABA能黑质被盖投射的调节：外侧和内侧SNr分别用于调节姿势肌张力和运动。我们得出结论，基底神经节疾病可能包括黑质被盖（基底神经节 - 脑干）系统功能障碍，进而导致异常肌张力和步态障碍的产生。
