底丘脑核:从环路、功能到深部脑刺激治疗帕金森病的靶点

Subthalamic nucleus: from circuits, functions to a deep brain stimulation target for the treatment of Parkinson's disease

底丘脑核(subthalamic nucleus,STN)是基底神经节(basal ganglia)环路中唯一的兴奋性谷氨酸能核团,不仅是经典间接通路中的关键节点,而且接受皮层的直接投射从而构成超直接通路(hyperdirect pathway),甚至被认为是驱动整个基底神经节活动的起搏器。STN由于其在基底神经节环路功能中的重要地位而成为临床上神经外科深部脑刺激(deep brain stimulation,DBS)治疗帕金森病(Parkinson’s disease,PD)的首选靶区之一。尽管STN-DBS可显著改善PD运动障碍,但其发挥效应的神经机制至今不明。本文简要综述了STN的传入、传出联系及它们在基底神经节环路中的功能,特别讨论了STN-DBS改善PD运动障碍机制的假说和最新研究进展。我们认为,对STN-DBS作用机制的认识不仅有助于临床PD治疗策略的发展,也有助于对基底神经节环路功能的深入理解。

The subthalamic nucleus （STN） is the only excitatory glutamatergic nucleus in the basal ganglia circuitry. It not only is a key node in the classical indirect pathway, but also forms the “hyperdirect” pathway directly connecting the cortex, and even is implicated as a pacemaker for activity of whole basal ganglia. Due to the key position of STN in the basal ganglia circuitry, the STN is an optimal target for deep brain stimulation （DBS） in the neurosurgical treatment of Parkinson’s disease （PD）. However, the therapeutic mechanisms underlying the amelioration of parkinsonian motor dysfunctions induced by DBS on STN remain enigmatic. This paper reviews recent progresses in the studies on the input-output configurations and functions of STN in the basal ganglia circuitry, and summarizes the hypotheses for mechanisms of DBS for the treatment of motor dysfunctions in PD. Studying on the DBS mechanisms will not only help to develop strategies for treatment of PD, but also contribute to the understanding of functions of the basal ganglia circuitry.