Basal ganglia neural responses during behaviorally effective deep brain stimulation of the subthalamic nucleus in rats performing a treadmill locomotion test

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	Basal ganglia neural responses during behaviorally effective deep brain stimulation of the subthalamic nucleus in rats performing a treadmill locomotion test
	Shi, LH ; Luo, F; Woodward, DJ ; Chang, JY ; J. Y. Chang
摘要	Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is an effective treatment for Parkinson's disease (PD). In spite of proven therapeutic success, the mechanism underlying the benefits of DBS has not been resolved. A multiple-channel single-unit recording technique was used in the present study to investigate basal ganglia (BG) neural responses during behaviorally effective DBS of the STN in a rat model of PD. Rats underwent unilateral dopamine (DA) depletion by injection of 6-hydroxyDA (6-OHDA) into one side of the medial forebrain bundle and subsequently developed a partial akinesia, which was assessed during the treadmill locomotion task. High frequency stimulation (HFS) of the STN restored normal treadmill locomotion behavior. Simultaneous recording of single unit activity in the striatum (STR), globus pallidus (GP), substantia nigra pars reticulata (SNr), and STN revealed a variety of neural responses during behaviorally effective HFS of the STN. Predominant inhibitory responses appeared in the STN stimulation site. Nearly equal numbers of excitatory and inhibitory responses were found in the GP and SNr, whereas more rebound excitatory responses were found in the STR. Mean firing rate did not change significantly in the STR, GP, and SNr, but significantly decreased in both sides of STN during DBS. A decrease in firing rate in the contralateral side of STN provides neural substrate for the clinical observation that unilateral DBS produces bilateral benefits in patients with PD. In addition to the firing rate changes, a decrease in burst firing was observed in the GP and STN. The present study indicates that DBS induces complex modulations of the BG circuit and further suggests that BG network reorganization, rather than a simple excitation or inhibition, may underlie the therapeutic effects of DBS in patients with PD.; Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is an effective treatment for Parkinson's disease (PD). In spite of proven therapeutic success, the mechanism underlying the benefits of DBS has not been resolved. A multiple-channel single-unit recording technique was used in the present study to investigate basal ganglia (BG) neural responses during behaviorally effective DBS of the STN in a rat model of PD. Rats underwent unilateral dopamine (DA) depletion by injection of 6-hydroxyDA (6-OHDA) into one side of the medial forebrain bundle and subsequently developed a partial akinesia, which was assessed during the treadmill locomotion task. High frequency stimulation (HFS) of the STN restored normal treadmill locomotion behavior. Simultaneous recording of single unit activity in the striatum (STR), globus pallidus (GP), substantia nigra pars reticulata (SNr), and STN revealed a variety of neural responses during behaviorally effective HFS of the STN. Predominant inhibitory responses appeared in the STN stimulation site. Nearly equal numbers of excitatory and inhibitory responses were found in the GP and SNr, whereas more rebound excitatory responses were found in the STR. Mean firing rate did not change significantly in the STR, GP, and SNr, but significantly decreased in both sides of STN during DBS. A decrease in firing rate in the contralateral side of STN provides neural substrate for the clinical observation that unilateral DBS produces bilateral benefits in patients with PD. In addition to the firing rate changes, a decrease in burst firing was observed in the GP and STN. The present study indicates that DBS induces complex modulations of the BG circuit and further suggests that BG network reorganization, rather than a simple excitation or inhibition, may underlie the therapeutic effects of DBS in patients with PD.
关键词	Parkinson's disease electrophysiology substantia nigra pars reticulata movement disorders striatum globus pallidus
学科领域	生理心理学/生物心理学
	2006-06-01
语种	英语
发表期刊	SYNAPSE
ISSN	0887-4476
卷号	59 期号:7 页码:445-457
期刊论文类型	Article
收录类别	SCI
WOS记录号	WOS:000237060200008
引用统计	被引频次：87[WOS] [WOS记录] [WOS相关记录]
文献类型	期刊论文
条目标识符	http://ir.psych.ac.cn/handle/311026/5215
专题	中国科学院心理研究所回溯数据库(1956-2010)
通讯作者	J. Y. Chang
作者单位	1.Wake Forest Univ, Sch Med, Dept Physiol & Pharmacol, Winston Salem, NC 27157 USA 2.Chinese Acad Sci, Inst Psychol, Beijing 100101, Peoples R China 3.Wake Forest Univ, Sch Med, Program Neurosci, Winston Salem, NC 27157 USA
推荐引用方式 GB/T 7714	Shi, LH,Luo, F,Woodward, DJ,et al. Basal ganglia neural responses during behaviorally effective deep brain stimulation of the subthalamic nucleus in rats performing a treadmill locomotion test[J]. SYNAPSE,2006,59(7):445-457.
APA	Shi, LH,Luo, F,Woodward, DJ,Chang, JY,&J. Y. Chang.(2006).Basal ganglia neural responses during behaviorally effective deep brain stimulation of the subthalamic nucleus in rats performing a treadmill locomotion test.SYNAPSE,59(7),445-457.
MLA	Shi, LH,et al."Basal ganglia neural responses during behaviorally effective deep brain stimulation of the subthalamic nucleus in rats performing a treadmill locomotion test".SYNAPSE 59.7(2006):445-457.

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