Functional correlates of exaggerated oscillatory activity in basal ganglia output in hemiparkinsonian rats.
Functional correlates of exaggerated oscillatory activity in basal ganglia output in hemiparkinsonian rats.
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DOI：
10.1016/j.expneurol.2014.07.010
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发表时间：
2014-11
影响因子：
5.3
通讯作者：
Walters, Judith R.
中科院分区：
文献类型：
--
作者：
Brazhnik, Elena;Novikov, Nikolay;McCoy, Alex J.;Cruz, Ana V.;Walters, Judith R.
关键词：
在植入深部脑刺激电极期间，在帕金森病（PD）患者的基底神经节中观察到放大的β范围（13-30 Hz）同步活动，并认为这是导致这种疾病的运动症状的原因。为了探索在PD大鼠模型中观察到的类似活动的翻译电位，在一系列行为期间，在单侧多巴胺细胞损伤的大鼠中表征了基底节输出的局部场电位（LFP）和尖峰活动。一个圆形的跑步机被用来评估活动在步行过程中，偏侧帕金森病大鼠可以保持稳定的步态时，定向同侧的病变半球，但在步行时，定向逆向病变效果较差。相对于非损伤半球，在损伤半球的β/低γ范围（12-40 Hz）内观察到黑质网状部（SNpr）LFP振荡活动和尖峰-LFP同步的急剧增加，尖峰-LFP夹带和LFP功率的主频率随行为状态而变化。在损伤后3周，在同侧踏车行走和梳理期间的平均显性夹带频率为34 Hz。其他行为与较低的平均夹带频率相关：27-28 Hz在警觉非行走和REM，17 Hz在休息和21 Hz在乌拉坦麻醉与感觉刺激。SNpr尖峰LFP夹带频率是稳定的，在个人的跑步机行走时期，但逐渐增加了数周后病变。相比之下，在25-40 Hz范围内的SNpr LFP功率在每个行走时期开始时最大，并在行走期间下降，在初始值的49%下稳定6分钟。结合1.5 s步进节律进一步调节功率。给予左旋多巴改善了逆行踏车行走，与多巴胺细胞损伤半球中SNpr 25-40 Hz LFP功率和尖峰同步的减少相关。这些作用可被肾上腺素能1A激动剂8-OH-DPAT逆转。虽然在偏侧帕金森病大鼠中持续运动活动期间观察到的突出尖峰-LFP锁相发生在比PD患者更高的频率处，但该动物模型的SNpr中的同步活动与PD患者的基底神经节记录的振荡活动有很多共同之处。结果支持该模型的潜力，为深入了解帕金森病的多巴胺和运动症状的损失引起的基底神经节输出的同步之间的关系。
Exaggerated beta range (13–30 Hz) synchronized activity is observed in the basal ganglia of Parkinson’s disease (PD) patients during implantation of deep brain stimulation electrodes and is thought to contribute to the motor symptoms of this disorder. To explore the translational potential of similar activity observed in a rat model of PD, local field potentials (LFP) and spiking activity in basal ganglia output were characterized in rats with unilateral dopamine cell lesion during a range of behaviors. A circular treadmill was used to assess activity during walking; hemiparkinsonian rats could maintain a steady gait when oriented ipsiversive to the lesioned hemisphere, but were less effective at walking when oriented contraversive to lesion. Dramatic increases in substantia nigra pars reticulata (SNpr) LFP oscillatory activity and spike-LFP synchronization were observed within the beta/low gamma range (12–40 Hz) in the lesioned hemisphere, relative to the non-lesioned hemisphere, with the dominant frequency of spike-LFP entrainment and LFP power varying with behavioral state. At 3 weeks post-lesion, the mean dominant entrainment frequency during ipsiversive treadmill walking and grooming was 34 Hz. Other behaviors were associated with lower mean entrainment frequencies: 27–28 Hz during alert non-walking and REM, 17 Hz during rest and 21 Hz during urethane anesthesia with sensory stimulation. SNpr spike-LFP entrainment frequency was stable during individual treadmill walking epochs, but increased gradually over weeks post-lesion. In contrast, SNpr LFP power in the 25–40 Hz range was greatest at the initiation of each walking epoch, and decreased during walking to stabilize by 6 min at 49% of initial values. Power was further modulated in conjunction with the 1.5 s stepping rhythm. Administration of L-dopa improved contraversive treadmill walking in correlation with a reduction in SNpr 25–40 Hz LFP power and spike synchronization in the dopamine cell lesioned hemisphere. These effects were reversed by the serotonergic 1A agonist, 8-OH-DPAT. While the prominent spike-LFP phase locking observed during ongoing motor activity in the hemiparkinsonian rats occurs at frequencies intriguingly higher than in PD patients, the synchronized activity in the SNpr of this animal model has much in common with oscillatory activity recorded from the basal ganglia of the PD patients. Results support the potential of this model for providing insight into relationships between synchronization of basal ganglia output induced by loss of dopamine and motor symptoms in PD.
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DOI：
10.3233/jpd-130204
发表时间：
2013-01-01
期刊：
Journal of Parkinson's disease
影响因子：
--
作者：
Ellens DJ;Leventhal DK
通讯作者：
Leventhal DK
影响因子：
2.5
作者：
Cruz AV;Mallet N;Magill PJ;Brown P;Averbeck BB
通讯作者：
Averbeck BB
影响因子：
5.3
作者：
de Solages, Camille;Hill, Bruce C.;Bronte-Stewart, Helen
通讯作者：
Bronte-Stewart, Helen
影响因子：
5.3
作者：
Chen, Chiung Chu;Hsu, Yi Ting;Brown, Peter
通讯作者：
Brown, Peter
影响因子：
2.5
作者：
BERGMAN, H;WICHMANN, T;DELONG, MR
通讯作者：
DELONG, MR