科研人员发现了从前脑到脑干的一个直接神经路径的证据，揭示了神经递质多巴胺用以控制运动的一种机制。根据目前的法则，运动依赖于通过多巴胺神经元传递的信号，这些神经元向基底核发出向上的突起。在基底核，这些突起向下延伸到脑干的一个运动控制中心。人们已经把这些上升的突起的丧失与帕金森疾病的运动缺陷联系在了一起。近来在猴子和大鼠身上的发现提示存在从多巴胺细胞直接向下通往运动控制中心的突起，Réjean Dubuc及其同事根据这些发现进行了研究。这组作者在一个七鳃鳗脊椎动物模型中使用红色、绿色和蓝色标记对投射到大脑不同区域的神经元进行了区分。这些发现表明许多多巴胺神经元绕过了基底核，直接投向运动控制中心，在那里，这些神经元的激活导致多巴胺的释放。这组作者说，这些发现改变了目前关于多巴胺如何控制运动的理解，而且可能对于帕金森疾病的运动相关症状有治疗意义。（生物谷 Bioon.com）
生物谷推荐的英文摘要
PNAS doi: 10.1073/pnas.1301125110
Forebrain dopamine neurons project down to a brainstem region controlling locomotion
Dimitri Ryczkoa, Swantje Grätscha, François Auclaira, Catherine Dubéa, Saskia Bergeronb, Michael H. Alpertc, Jackson J. Conec, Mitchell F. Roitmanc, Simon Alfordc, and Réjean Dubuca,b,1
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.
