The Molecular Neuropharmacology Laboratory and the Eye-Brain Research Center, The State Key Laboratory of Ophthalmology, Optometry and Vision Science, School of Ophthalmology & Optometry and Eye Hospital, Wenzhou Medical University, Wenzhou, China.
Oujiang Laboratory (Zhejiang Laboratory for Regenerative Medicine, Vision and Brain Health), School of Ophthalmology & Optometry and Eye Hospital, Wenzhou Medical University, Wenzhou, China.
J Physiol. 2024 Aug;602(15):3755-3768. doi: 10.1113/JP286046. Epub 2024 Jul 9.
Volitional modulation of neural activity is not confined to the cortex but extends to various brain regions. Yet, it remains unclear whether neurons in the basal ganglia structure, the external globus pallidus (GPe), can be volitionally controlled. Here, we employed a volitional conditioning task to compare the volitional modulation of GPe and primary motor cortex (M1) neurons as well as the underlying circuits and control mechanisms. The results revealed that the volitional modulation of GPe neuronal activity engaged both M1 and substantia nigra pars reticulata (SNr) neurons, indicating the involvement of the cortex-GPe-SNr loop. In contrast, the volitional modulation of M1 neurons primarily occurred through the engagement of M1 local circuitry. Furthermore, lesioning M1 neurons did not affect the volitional learning or volitional control signal in GPe, whereas lesioning of GPe neurons impaired the learning process for the volitional modulation of M1 neuronal activity at the intermediate stage. Additionally, lesion of GPe neurons enhanced M1 neuronal activity when performing the volitional control task without reward delivery and a random reward test. Taken together, our findings demonstrated that GPe neurons could be volitionally controlled by engagement of the cortical-basal ganglia circuit and inhibit learning process for the volitional modulation of M1 neuronal activity by regulating M1 neuronal activity. Thus, GPe neurons can be effectively harnessed for independent volitional modulation for neurorehabilitation in patients with cortical damage. KEY POINTS: The cortical-basal ganglia circuit contributes to the volitional modulation of GPe neurons. Volitional modulation of M1 neuronal activity mainly engages M1 local circuitry. Bilateral GPe lesioning impedes volitional learning at the intermediate stages. Lesioning of GPe neurons inhibits volitional learning process by regulating M1 neuronal activity.
自愿调节神经活动不仅局限于皮层，还扩展到各种脑区。然而，尚不清楚基底神经节结构的苍白球外部区（GPe）神经元是否可以被自愿控制。在这里，我们采用自愿条件反射任务来比较 GPe 和初级运动皮层（M1）神经元的自愿调节，以及潜在的回路和控制机制。结果表明，GPe 神经元活动的自愿调节既涉及 M1 神经元，也涉及黑质网状部（SNr）神经元，表明涉及皮层-GPe-SNr 回路。相比之下，M1 神经元的自愿调节主要通过 M1 局部回路的参与来实现。此外，M1 神经元的损伤不影响 GPe 中的自愿学习或自愿控制信号，而 GPe 神经元的损伤则损害了 M1 神经元活动自愿调节的学习过程的中间阶段。此外，GPe 神经元的损伤会增强执行自愿控制任务时的 M1 神经元活动，而没有奖励传递和随机奖励测试。总之，我们的发现表明，GPe 神经元可以通过皮层-基底神经节回路的参与被自愿控制，并通过调节 M1 神经元活动来抑制 M1 神经元活动自愿调节的学习过程。因此，GPe 神经元可以有效地用于皮质损伤患者的神经康复中的独立自愿调节。关键点：皮层-基底神经节回路有助于 GPe 神经元的自愿调节。M1 神经元活动的自愿调节主要涉及 M1 局部回路。双侧 GPe 损伤会阻碍中间阶段的自愿学习。GPe 神经元的损伤通过调节 M1 神经元活动来抑制自愿学习过程。
