Chang Jing-Yu, Shi Li-Hong, Luo Fei, Woodward Donald J
Department of Physiology and Pharmacology, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA.
Exp Brain Res. 2006 Jun;172(2):193-207. doi: 10.1007/s00221-005-0312-7. Epub 2005 Dec 21.
To investigate basal ganglia (BG) neural responses to dopamine (DA) depletion, multiple channel, single unit recording was carried out in freely moving rats performing a treadmill locomotion task. Single unit activity from 64 microelectrodes in the striatum (STR), globus pallidus (GP), subthalamic nucleus (STN) and substantia nigra pars reticulata (SNr) was recorded simultaneously before and after a unilateral DA lesion induced by microinjection of 6-hydroxydopamine (6-OHDA) into the medial forebrain bundle. The DA lesion resulted in an impairment of treadmill walking manifested by a significant decrease in swing time of both forelimbs. The stance time, however, increased significantly only in ipsilateral (good) forelimbs, reflecting compensatory changes in the good limb for motor deficits. Neural activity in the STR and GP ipsilateral to the lesion decreased during the 7-day period following the DA lesion. Conversely, an increase in spike discharges appeared in the ipsilateral SNr and STN several days after the DA lesion. Changes in the type of neural response associated with treadmill locomotion were also found in some neurons after DA depletion. Such changes were most prominent in the STR. Limb movement-related neural activity increased significantly mainly in the SNr. Additionally, neural responses to the tone cue associated with the onset of the treadmill diminished greatly in the lesioned side of the BG. Increased activity in SNr neurons is consistent with the concept that inhibition of thalamus contributes to hypokinesis in the absence of DA. Substantial decrease in striatal activity supports a concept that DA loss leads to a global suppression of recurrent cortical striatal thalamic activity that degrades normal information flow in Parkinson's diseases.
为了研究基底神经节（BG）对多巴胺（DA）耗竭的神经反应，在自由活动的大鼠执行跑步机运动任务时进行了多通道单单元记录。在向内侧前脑束微量注射6-羟基多巴胺（6-OHDA）诱导单侧DA损伤前后，同时记录纹状体（STR）、苍白球（GP）、丘脑底核（STN）和黑质网状部（SNr）中64个微电极的单单元活动。DA损伤导致跑步机行走受损，表现为双侧前肢摆动时间显著缩短。然而，站立时间仅在同侧（健侧）前肢显著增加，反映了健侧肢体对运动缺陷的代偿性变化。DA损伤后7天内，损伤同侧STR和GP中的神经活动减少。相反，DA损伤几天后，同侧SNr和STN中出现了放电尖峰增加。DA耗竭后，一些神经元中还发现了与跑步机运动相关的神经反应类型的变化。这种变化在STR中最为明显。与肢体运动相关的神经活动主要在SNr中显著增加。此外，BG损伤侧对与跑步机启动相关的音调提示的神经反应大大减弱。SNr神经元活动增加与以下概念一致，即在缺乏DA的情况下，丘脑抑制导致运动迟缓。纹状体活动的大幅下降支持了这样一种概念，即DA缺失导致对复发性皮质-纹状体-丘脑活动的全面抑制，从而破坏了帕金森病中的正常信息流。
