Departament de Ciències Matemàtiques i Informàtica, Universitat de les Illes Balears, Palma 07122, Spain.
Institute of Applied Computing and Community Code, Palma 07122, Spain.
Proc Natl Acad Sci U S A. 2024 Nov 19;121(47):e2408505121. doi: 10.1073/pnas.2408505121. Epub 2024 Nov 13.
Reactive inhibitory control is crucial for survival. Traditionally, this control in mammals was attributed solely to the hyperdirect pathway, with cortical control signals flowing unidirectionally from the subthalamic nucleus (STN) to basal ganglia output regions. Yet recent findings have put this model into question, suggesting that the STN is assisted in stopping actions through ascending control signals to the striatum mediated by the external globus pallidus (GPe). Here, we investigate this suggestion by harnessing a biologically constrained spiking model of the cortico-basal ganglia-thalamic (CBGT) circuit that includes pallidostriatal pathways originating from arkypallidal neurons. Through a series of experiments probing the interaction between three critical inhibitory nodes (the STN, arkypallidal cells, and indirect pathway spiny projection neurons), we find that the GPe acts as a critical mediator of both ascending and descending inhibitory signals in the CBGT circuit. In particular, pallidostriatal pathways regulate this process by weakening the direct pathway dominance of the evidence accumulation process driving decisions, which increases the relative suppressive influence of the indirect pathway on basal ganglia output. These findings delineate how pallidostriatal pathways can facilitate action cancellation by managing the bidirectional flow of information within CBGT circuits.
反应性抑制控制对于生存至关重要。传统上,哺乳动物的这种控制仅归因于直接通路,皮质控制信号从丘脑底核(STN)单向流向基底节输出区域。然而,最近的发现对该模型提出了质疑,表明 STN 通过由苍白球外段(GPe)介导的上升控制信号辅助停止动作。在这里,我们通过利用包括源自弓状核神经元的苍白球纹状体通路的皮质基底节丘脑(CBGT)电路的生物约束尖峰模型来研究这一建议。通过一系列实验探测三个关键抑制节点(STN、弓状核细胞和间接通路棘突投射神经元)之间的相互作用,我们发现 GPe 作为 CBGT 电路中上升和下降抑制信号的关键介导者。特别是,苍白球纹状体通路通过削弱驱动决策的证据积累过程中的直接通路优势来调节这个过程,这增加了间接通路对基底节输出的相对抑制影响。这些发现描绘了苍白球纹状体通路如何通过管理 CBGT 电路内信息的双向流动来促进动作取消。