Fallah Michel, Udobi Kenea C, Swiatek Aleksandra E, Scott Chelsea B, Evans Rebekah C
Interdisciplinary Program in Neuroscience, Georgetown University, Washington, DC, USA 20007.
Department of Neuroscience, Georgetown University Medical Center, Washington, DC, USA 20007.
bioRxiv. 2024 Aug 6:2024.08.05.606694. doi: 10.1101/2024.08.05.606694.
The canonical basal ganglia model predicts that the substantia nigra (SNr) and the globus pallidus (GPe) will have specific effects on locomotion: the SNr inhibiting locomotion and the GPe enhancing it. In this manuscript, we use optogenetics to show that a projection-defined neural subpopulation within each structure exerts non-canonical effects on locomotion. These non-canonical subpopulations are defined by their projection to the pedunculopontine nucleus (PPN) and mediate opposing effects on reward. To understand how these structures differentially modulate the PPN, we use whole-cell recording with optogenetics to comprehensively dissect the SNr and GPe connections to regionally- and molecularly-defined populations of PPN neurons. The SNr inhibits all PPN subtypes, but most strongly inhibits caudal glutamatergic neurons. The GPe selectively inhibits caudal glutamatergic and GABAergic neurons, avoiding both cholinergic and rostral cells. This circuit characterization reveals non-canonical basal ganglia pathways for locomotion and valence.
经典的基底神经节模型预测，黑质（SNr）和苍白球外侧部（GPe）对运动将产生特定影响：SNr抑制运动，而GPe增强运动。在本论文中，我们利用光遗传学表明，每个结构内一个由投射定义的神经亚群对运动发挥非经典作用。这些非经典亚群由其向脚桥核（PPN）的投射所定义，并介导对奖赏的相反作用。为了解这些结构如何差异地调节PPN，我们采用光遗传学全细胞记录来全面剖析SNr和GPe与按区域和分子定义的PPN神经元群体的连接。SNr抑制所有PPN亚型，但对尾侧谷氨酸能神经元的抑制作用最强。GPe选择性抑制尾侧谷氨酸能和GABA能神经元，而不影响胆碱能神经元和吻侧细胞。这种环路特征揭示了运动和效价的非经典基底神经节通路。
