Capozzo Annamaria, Vitale Flora, Mattei Claudia, Mazzone Paolo, Scarnati Eugenio
Department of Biotechnological and Applied Clinical Sciences (DISCAB), University of L'Aquila, Via Vetoio, Coppito 2, I-67100 L'Aquila, Italy.
Unit of Functional Neurosurgery, CTO Alesini Hospital ASL Rome C, Via San Nemesio 21, 00145 Rome, Italy.
Behav Brain Res. 2014 Sep 1;271:333-42. doi: 10.1016/j.bbr.2014.06.033. Epub 2014 Jun 21.
The pedunculopontine tegmental nucleus (PPTg) relays basal ganglia signals to the thalamus, lower brainstem and spinal cord. Using the 6-hydroxydopamine (6-OHDA) rat model of parkinsonism, we investigated whether deep brain stimulation (DBS) of the PPTg (40 Hz, 60 μs, 200-400 μA) may influence the preparative and executive phases in a conditioned behavioural task, and the motor asymmetries induced by apomorphine. In the conditioned task, rats had to press two levers according to a fixed delay paradigm. The 6-OHDA lesion was placed in the right medial forebrain bundle, i.e. contralaterally to the preferred forepaw used by rats to press levers in the adopted task. The stimulating electrode was implanted in the right PPTg, i.e. contralateral to left side, which was expected to be most affected. The lesion significantly reduced correct responses from 63.4% to 16.6%. PPTg-DBS effects were episodic; however, when rats successfully performed in the task (18.9%), reaction time (468.8 ± 36.5 ms) was significantly increased (589.9 ± 45.9 ms), but not improved by PPTg-DBS (646.7 ± 33.8 ms). Movement time was significantly increased following the lesion (649.2 ± 42.6 ms vs. 810.9 ± 53.0 ms), but significantly reduced by PPTg-DBS (820.4 ± 39.4 ms) compared to sham PPTg-DBS (979.8 ± 47.6 ms). In a second group of lesioned rats, rotations induced by apomorphine were significantly reduced by PPTg-DBS compared to sham PPTg-DBS (12.2 ± 0.6 vs. 9.5 ± 0.4 mean turns/min). Thus, it appears that specific aspects of motor deficits in 6-OHDA-lesioned rats may be modulated by PPTg-DBS.
脚桥被盖核（PPTg）将基底神经节的信号传递至丘脑、低位脑干和脊髓。我们使用帕金森病的6-羟基多巴胺（6-OHDA）大鼠模型，研究了对PPTg进行深部脑刺激（DBS，40赫兹，60微秒，200 - 400微安）是否会影响一项条件性行为任务中的准备阶段和执行阶段，以及阿扑吗啡诱导的运动不对称性。在该条件任务中，大鼠必须根据固定延迟范式按压两个杠杆。6-OHDA损伤置于右侧内侧前脑束，即与大鼠在采用的任务中用于按压杠杆的偏好前爪对侧。刺激电极植入右侧PPTg，即与预期受影响最大的左侧对侧。损伤使正确反应率从63.4%显著降低至16.6%。PPTg-DBS的效果是间歇性的；然而，当大鼠在任务中成功执行时（18.9%），反应时间（468.8±36.5毫秒）显著增加（589.9±45.9毫秒），但PPTg-DBS并未使其改善（646.7±33.8毫秒）。损伤后运动时间显著增加（649.2±42.6毫秒对810.9±53.0毫秒），但与假手术PPTg-DBS（979.8±47.6毫秒）相比，PPTg-DBS使其显著缩短（820.4±39.4毫秒）。在第二组损伤大鼠中，与假手术PPTg-DBS相比，PPTg-DBS使阿扑吗啡诱导的旋转显著减少（平均每分钟旋转次数：12.2±0.6对9.5±0.4）。因此，6-OHDA损伤大鼠运动缺陷的特定方面似乎可被PPTg-DBS调节。
