Department of Life, Health and Environmental Sciences, University of L'Aquila, Via Vetoio, 67100 L'Aquila, Italy.
Behav Brain Res. 2013 Aug 1;250:326-33. doi: 10.1016/j.bbr.2013.05.020. Epub 2013 May 21.
Patients with Parkinson's disease show unbalanced capability to manage self-paced vs externally driven movements, or automatic-associated movements with respect to the intended voluntary movements. We studied the effect of a selective loss of dopaminergic terminals within the striatum and the execution of a well-learned set-shifting task as revealed using tyrosine hydroxylase immunoreactivity and magnetic resonance imaging in the rat. We found that, both in the externally cued condition, and in the externally-internally driven switching task, the cue-dependent constraints interfered with motor readiness in over training condition. The unilateral dopaminergic striatal depletion enhanced the switch-induced performance differences in favour of the internally-externally cued transition. Dopamine depleted rats, in fact, were impaired to produce an alternative motion when task switching required to change from an over trained behaviour, towards an alternative self-paced response. The comparative analysis of behavioural, tyrosine hydroxylase immunoreactivity and magnetic resonance imaging data, revealed a shrinkage of the lesioned striatum, and an enlargement of the ipsilateral ventricle that could provide useful markers for monitoring pathological changes occurring during early stages of Parkinson's disease in vivo.
帕金森病患者在自我调节与外部驱动运动或自动关联运动与预期的自愿运动之间表现出不平衡的能力。我们研究了纹状体多巴胺能末梢选择性丧失和使用酪氨酸羟化酶免疫反应性和磁共振成像在大鼠中揭示的一套学习好的转变任务执行对这一现象的影响。我们发现,无论是在外部提示条件下,还是在外部内部驱动的转换任务中,提示依赖性约束都会干扰过度训练条件下的运动准备。单侧多巴胺能纹状体耗竭增强了开关诱导的性能差异,有利于内部外部提示的转换。事实上,当任务转换需要从过度训练的行为转变为替代的自我调节反应时,多巴胺耗竭的大鼠难以产生替代运动。行为、酪氨酸羟化酶免疫反应性和磁共振成像数据的比较分析显示,损伤纹状体缩小,同侧脑室扩大,这可能为监测帕金森病早期体内发生的病理变化提供有用的标志物。