University of Amsterdam, Science Park 904, 1098XH Amsterdam, The Netherlands.
Ernst Strüngmann Institute, Deutschordenstraße 46, 60528 Frankfurt am Main, Germany.
Neuroscience. 2017 Dec 16;366:62-69. doi: 10.1016/j.neuroscience.2017.10.009. Epub 2017 Oct 14.
The Ventral Tegmental Area (VTA) contains a considerable population of rhythmically firing dopaminergic neurons, which are influenced by auto-inhibition due to extra-synaptic dopamine release resulting in volume transmission. Using a Multi-Electrode-Array we simultaneously recorded in vitro from multiple VTA dopamine neurons in the rat and studied their mutual interactions. We observed that the dopamine sensitivity (EC50) of the neurons (i.e. the relation between dopamine concentration and firing rate) was quite variable within the recorded population. The interactions between pairs of neurons were quantified using the Granger causality. We found that the dopamine sensitivity determined the role of a neuron in the local VTA population. Highly sensitive neurons became followers (of the population rhythm), whereas less sensitive dopamine neurons played a more leading role. This was confirmed by the application of sulpiride which reduces the dopamine sensitivity of all neurons through competition and abolishes the structure in the interactions. These findings imply that therapeutics, which have an easy to understand effect on firing rate, could have a more complicated effect on the functional organization of the local VTA population, through volume transmission principles.
腹侧被盖区（VTA）含有相当数量的节律性放电多巴胺能神经元，这些神经元受到由于突触外多巴胺释放导致的容积传递的自抑制的影响。我们使用多电极阵列在体外同时记录大鼠 VTA 多巴胺神经元，并研究了它们之间的相互作用。我们观察到，神经元的多巴胺敏感性（EC50）在记录的神经元群体中差异很大。使用格兰杰因果关系来量化神经元对之间的相互作用。我们发现，多巴胺敏感性决定了神经元在局部 VTA 群体中的作用。高敏感神经元成为追随者（群体节律的追随者），而低敏感多巴胺神经元则发挥更主导的作用。这通过应用舒必利得到了证实，舒必利通过竞争降低所有神经元的多巴胺敏感性，并消除相互作用中的结构。这些发现表明，通过容积传递原理，对放电率有简单易懂影响的治疗方法可能对局部 VTA 群体的功能组织产生更复杂的影响。
