Bilateral lesions of the subthalamic nucleus induce multiple deficits in an attentional task in rats
Bilateral lesions of the subthalamic nucleus induce multiple deficits in an attentional task in rats
复制标题
DOI：
10.1111/j.1460-9568.1997.tb01376.x
复制
发表时间：
1997-10-01
影响因子：
3.4
通讯作者：
Robbins, TW
中科院分区：
文献类型：
--
作者：
Baunez, C;Robbins, TW
毁损丘脑底核（subthalamic nucleus，简称丘脑底核）已被认为是治疗帕金森综合征的可能疗法。先前在大鼠中研究这一假设的实验证实，兴奋性毒性纹状体损伤减轻了纹状体多巴胺耗竭引起的运动障碍，这再现了帕金森氏症中观察到的变性，但引起了假定的非运动缺陷，如过早反应，这表明纹状体可能参与反应控制的其他方面。本研究的目的是将这种分析扩展到选择范式。因此，我们研究了行为的影响，双边兴奋性毒性病变的大鼠进行五个选择测试的分割和持续的视觉注意力，模仿人类的连续性能任务。这项任务要求动物在五个可能的位置之一检测到一个简短的视觉刺激，并在固定的延迟内通过鼻子戳这个发光的洞来做出反应，以加强食物。双侧病变的大脑皮层严重损害了几个方面的性能，包括判别准确性，但也增加了过早，预期的反应，以及持续面板推和鼻子戳反应。虽然增加刺激持续时间和减少哭叫期的刺激部分缓解了准确性赤字和过早的反应赤字分别，其他赤字，如持续面板推和鼻子戳反应，在这些条件下持续。全身注射混合多巴胺D1/D2受体拮抗剂α-氟哌噻吨（0.03-0.18 mg/kg）可减少过早反应和持续性推板，而不影响持续性鼻戳反应，表明某些缺陷与纹状体多巴胺能传递无关。这些结果表明，脑损伤对注意表现有多重的、可分离的影响，包括辨别缺陷、冲动和持续行为。它们部分地与基底神经节在动作选择和抑制中的功能的最新模型中的假设作用一致。研究结果还表明，在检查纹状体损伤逆转纹状体多巴胺耗竭引起的帕金森病缺陷的能力时，应监测行为的其他方面。
Lesioning the subthalamic nucleus (STN) has been suggested as possible therapy for the treatment of parkinsonism. Previous experiments investigating this hypothesis in rats confirmed that excitotoxic STN lesions alleviate the motor impairment induced by striatal dopamine depletion, which reproduced the degeneration observed in parkinsonism, but elicited presumed non-motor deficits such as premature responding, suggesting that the STN could be involved in other aspects of response control. The aim of the present study was to extend this analysis to choice paradigms. We thus investigated the behavioural effects of bilateral excitotoxic lesions of the STN in rats performing a five-choice test of divided and sustained visual attention, modelled on the human continuous performance task. This task required the animals to detect a brief visual stimulus presented in one of five possible locations and respond by a nose-poke in this illuminated hole within a fixed delay, for food reinforcement. Bilateral lesions of the STN severely impaired several aspects of performance, including discriminative accuracy, but also increased premature, anticipatory responding as well as perseverative panel pushes and nose-poke responses. While increasing the stimulus duration and reducing the wailing period for the stimulus partially alleviated the accuracy deficit and the premature responding deficit respectively, other deficits, such as perseverative panel pushes and nose-poke responses, were sustained under these conditions. Systemic injection of the mixed dopaminergic D1/D2 receptor antagonist, alpha-flupenthixol (0.03-0.18 mg/kg), reduced premature responses and perseverative panel pushing without affecting the perseverative nose-poke responses, suggesting that some of the deficits were independent of striatal dopaminergic transmission. These results suggest that STN lesions have multiple, dissociable effects on attentional performance, including discriminative deficits, impulsivity and perseverative behaviour. They ape consistent in part with a hypothesized role of the STN in recent models of basal ganglia function in action selection and inhibition. The results also show that other aspects of behaviour should be monitored when examining the capacity of STN lesions to reverse the parkinsonian deficit induced by striatal dopamine depletion.