多巴胺对猕猴额叶随机延缓反应作业相关神经元活动的影响(英文)

Effects of Dopamine on Frontal Neuron Activity of Rhesus Monkeys During Randomly Delayed Reaction Time Task

在猕猴执行随机延缓反应作业的同时,观察了微电泳多巴胺及其受体阻断剂氟哌啶醇对额叶作业相关神经元自发放电活动和诱发反应的影响。在该作业中,延缓期在1～4秒之间随机变化,在延缓期动物必须高度注意黄灯信号的出现,如稍不注意就会导致操作错误。在反应期,动物要在1秒钟内作出放开杠杆的反应。在实验中,对109个作业相关神经元观察了多巴胺的效应,这些神经元在作业间期共表现出神经元反应134个。神经元反应多出现在延缓期(48个)和反应期(72个),约占反应总数的90%。有近60%的神经元(61/109)对多巴胺敏感,多巴胺对神经元的自发放电活动既有兴奋效应(21/61),又有抑制效应(40/61),但以抑制效应为主。在延缓期出现反应的神经元中有31个(31/48)对多巴胺敏感,多巴胺对神经元的诱发反应主要起抑制作用(23/31);在反应期出现反应的神经元中有44个(44/72)对多巴胺敏感,多巴胺也以抑制作用为主(32/44),即使神经元的放电活动减弱。对54个(54/61)多巴胺敏感神经元观察了氟哌啶醇的效应,氟哌啶醇的效应与多巴胺相反,并能阻断多巴胺的效应。形态学检查表明,多巴胺敏感性神经元主要分布在大脑额叶弓状沟上支的内侧部。本实验表明,在延缓期和反应期出现放电变化的额叶神经元半数以上都对多巴胺敏感,且以抑制效应为主。由于作业的这两个时期分别与注意和视觉指导下的运动有关,因此,在视-运动耦合以及注意等过程中,在大脑额叶有多巴胺敏感神经元参与,而且主要是参与神经元活动的抑制过程。

Effects of dopamine on frontal neuron activity were studied on 2awake monkeys during performing a randomly delayed reaction time task.In the task,theduration of delay period was set pseudo-randomly between 1 to 4s in order that the monkeyhad to watch the signal panel attentively to make a correct response,and the monkey oughtto release the lever within 1s in reaction period.After the monkey had learned the task,sin-gle neuronal activity was recorded from the frontal cortex during the performance,anddopamine and haloperidol were applied iontophoretically to the task-related neurons.Of the109 task-related neurons tested,61 neurons(56%)were sensitive to dopamine.Sponta-neous firing rate was decreased in 40 neurons during the application of dopamine,and in-creased in the remaining 21.The 109 neurons showed 134 changes in discharge rate in the 4periods.Although neuronal responses appeared in all the 4 periods of the task,the majority(nearly 90%)were in delay period(n=48)and reaction period(n=72).Of the 48 neu-rons showing activity changes in delay period,31 were sensitive to dopamine,and 23 ofthem decreased in discharge rate.In reaction period,44 neurons(44/72)were sensitive todopamine,and 32 decreased in firing rate.54 of the 61 dopamine-sensitive neurons weretested with haloperidol.The effect of haloperidol was contrary to that of dopamine.Histo-logical study showed that most of the neurons examined were located in a circumscribed areamedial to the superior ramus of the arcuate sulcus,including prefrontal and premotor areas.The results indicate that dopamine mainly decreases both the spontaneous activity andtask-related activity of the frontal neurons.It is suggested that dopamine may play an im-portant role in attention and visually guided movement,particularly in the inhibitory aspectof the neuronal processes.