Groupe de Recherche sur le Système Nerveux Central, Département de Physiologie, Université de Montréal, Montréal, QC, Canada H3C 3J7.
Proc Natl Acad Sci U S A. 2013 Aug 20;110(34):E3235-42. doi: 10.1073/pnas.1301125110. Epub 2013 Aug 5.
The contribution of dopamine (DA) to locomotor control is traditionally attributed to ascending dopaminergic projections from the substantia nigra pars compacta and the ventral tegmental area to the basal ganglia, which in turn project down to the mesencephalic locomotor region (MLR), a brainstem region controlling locomotion in vertebrates. However, a dopaminergic innervation of the pedunculopontine nucleus, considered part of the MLR, was recently identified in the monkey. The origin and role of this dopaminergic input are unknown. We addressed these questions in a basal vertebrate, the lamprey. Here we report a functional descending dopaminergic pathway from the posterior tuberculum (PT; homologous to the substantia nigra pars compacta and/or ventral tegmental area of mammals) to the MLR. By using triple labeling, we found that dopaminergic cells from the PT not only project an ascending pathway to the striatum, but send a descending projection to the MLR. In an isolated brain preparation, PT stimulation elicited excitatory synaptic inputs into patch-clamped MLR cells, accompanied by activity in reticulospinal cells. By using voltammetry coupled with electrophysiological recordings, we demonstrate that PT stimulation evoked DA release in the MLR, together with the activation of reticulospinal cells. In a semi-intact preparation, stimulation of the PT elicited reticulospinal activity together with locomotor movements. Microinjections of a D1 antagonist in the MLR decreased the locomotor output elicited by PT stimulation, whereas injection of DA had an opposite effect. It appears that this descending dopaminergic pathway has a modulatory role on MLR cells that are known to receive glutamatergic projections and promotes locomotor output.
多巴胺（DA）对运动控制的贡献传统上归因于来自黑质致密部和腹侧被盖区的上行多巴胺能投射到基底节，基底节反过来投射到中脑运动区（MLR），MLR 是控制脊椎动物运动的脑干区域。然而，最近在猴子中发现了 pedunculopontine 核的多巴胺能神经支配，该核被认为是 MLR 的一部分。该多巴胺能传入的起源和作用尚不清楚。我们在一种基础脊椎动物——七鳃鳗中解决了这些问题。在这里，我们报告了一条来自后结节（PT；与哺乳动物的黑质致密部和/或腹侧被盖区同源）到 MLR 的功能性下行多巴胺能通路。通过使用三重标记，我们发现来自 PT 的多巴胺能细胞不仅投射出一条上行通路到纹状体，而且还投射出一条下行通路到 MLR。在一个分离的脑制备物中，PT 刺激诱发了被钳制的 MLR 细胞中的兴奋性突触输入，同时伴有网状脊髓细胞的活动。通过将伏安法与电生理记录相结合，我们证明了 PT 刺激在 MLR 中诱发了 DA 释放，同时激活了网状脊髓细胞。在半完整的制备物中，PT 刺激诱发了网状脊髓活动和运动。在 MLR 中注射 D1 拮抗剂会减少由 PT 刺激引起的运动输出，而 DA 的注射则有相反的效果。似乎这条下行多巴胺能通路对已知接收谷氨酸能投射的 MLR 细胞具有调节作用，并促进运动输出。
