Functinal Role of Modular Organization in the Basal Ganglia

本研究的目的是阐明黑质纹状体多巴胺系统在通过行为病毒调节获得新活动中的作用。用3只猕猴（Macaca fuscata）进行了经典条件反射实验。在大约三周的时间里，所有的动物都获得了行为条件反射，并且口腔面部的运动也变得刻板化了，这些运动是为了消耗放在嘴边的勺子上的奖励水。纹状体中超过60%的紧张性活跃神经元（TANs）对条件反射点击做出反应。然后，我们通过向纹状体单侧注入多巴胺能神经毒素MPTP两周来消耗黑质纹状体多巴胺。在家里的笼子里，动物表现出转向MPTP注射侧的趋势，这是单侧多巴胺消耗的迹象。在条件反射点击刺激后，习得的条件性面部运动变得笨拙而非自动。令人惊讶的是，在MPTP注射侧，只有非常少的TANs（10-15%）对条件点击有反应，而对侧完整纹状体的TANs则保持了反应。全身注射多巴胺受体激动剂阿波啡恢复了刻板行为和TAN反应，从而表明MPTP对获得性行为和神经元活性的显著影响是通过多巴胺系统特异性诱导的。这些结果对黑质纹状体多巴胺系统在行为学习和记忆中的作用提出了假设。在行为学习的初始阶段，黑质纹状体系统发送大量带有“动机”或“激励”信息的多巴胺。这将使纹状体神经元获得对条件刺激的反应，同时在黑纹状体神经元的纹状体末端释放多巴胺。学习建立后，黑质纹状体系统向纹状体神经元发送基线量的多巴胺，以表达习得的活动，从而导致刻板的条件行为。少

The purpose of the present investigation was to clarify role of nigrostriatal dopamine system in in an acquisition of new activity through behaviral conditioning. Classical conditioning of an auditory click with reward juice was used using 3 macaque mankeys (Macaca fuscata). In about three weeks, all animals acquied the behavioral conditioning and the orofacial movements to consume reward water delivered upon the spoon in front of mouth became stereotyped. More that 60% of tonically active neurons (TANs) recorded in the striatum became responsive to the conditioning click. Then, we depleted nigrostriatal dopamine through an infusion of dopaminergic neurotoxin MPTP for two weeks into the striatum unilaterally. Animals showed a tandency to turn to the MPTP injected side in their home cages, which was the sign of unilateral dopamine depletion. The acquierd conditioned orofacial movements after conditioning click stimuli became clumsy and not automatic. Quite surprisingly, only very small … More number (10-15%) of TANs in the MPTP injected side showed responses to conditioning click, while the responses of TANs in the contralateral intact striatum was preserved. Systemic injection of dopamine receptor agonist, apomorphine, restored stereotyped behavior and TAN responses, and thus demonstrated that the dramatic effect of MPTP on the acquired behavior and neuronal sctivity was induced specifically through dopamine system. These results an hypothesis on the function of nigrostriatal dopamine system in behavioral learning and memory. In an intial stage of behavioral learning, nigrostriatal system send large amount of dopamine with an information of "motivation" or "incentive". This would let striatal neurons to acquire responses to conditioning stimulus occurred in conjunction with dopamine release at striatal terminals of nigrostriatal neurons. After learning is established, the nigrostriatal system send base line amount of dopamine for the striatal neurons to express the learned activity which will lead to stereotyped conditioned behavior. Less