Department of Neuroscience, Nobel Institute for Neurophysiology, Karolinska Institute, SE-171 77 Stockholm, Sweden.
J Neurosci. 2013 May 1;33(18):8045-54. doi: 10.1523/JNEUROSCI.5881-12.2013.
The functions of the basal ganglia are critically dependent on dopamine. In mammals, dopamine differentially modulates the excitability of the direct and indirect striatal projection neurons, and these populations selectively express dopamine D1 and D2 receptors, respectively. Although the detailed organization of the basal ganglia is conserved throughout the vertebrate phylum, it was unknown whether the differential dopamine modulation of the direct and indirect pathways is present in non-mammalian species. We aim here to determine whether the receptor expression and opposing dopaminergic modulation of the direct and indirect pathways is present in one of the phylogenetically oldest vertebrates, the river lamprey. Using in situ hybridization and patch-clamp recordings, we show that D1 receptors are almost exclusively expressed in the striatal neurons projecting directly to the homolog of the substantia nigra pars reticulata. In addition, the majority of striatal neurons projecting to the homolog of the globus pallidus interna/globus pallidus externa express D1 or D2 receptors. As in mammals, application of dopamine receptor agonists differentially modulates the excitability of these neurons, increasing the excitability of the D1-expressing neurons and decreasing the excitability of D2-expressing neurons. Our results suggest that the segregated expression of the D1 and D2 receptors in the direct and indirect striatal projection neurons has been conserved across the vertebrate phylum. Because dopamine receptor agonists differentially modulate these pathways, increasing the excitability of the direct pathway and decreasing the excitability of the indirect pathway, this organization may be conserved as a mechanism that biases the networks toward action selection.
基底神经节的功能严重依赖于多巴胺。在哺乳动物中，多巴胺对直接和间接纹状体投射神经元的兴奋性有差异调节作用，而这两种神经元群体分别选择性地表达多巴胺 D1 和 D2 受体。尽管基底神经节的详细结构在整个脊椎动物门中都得到了保守，但尚不清楚这种对直接和间接通路的多巴胺差异调节是否存在于非哺乳动物物种中。我们旨在确定在一种进化上最古老的脊椎动物——七鳃鳗中，是否存在直接和间接通路的受体表达和相反的多巴胺调节。通过原位杂交和膜片钳记录，我们表明 D1 受体几乎仅在投射到与黑质网状部同源的纹状体神经元中表达。此外，投射到与苍白球内/外核同源的大多数纹状体神经元表达 D1 或 D2 受体。与哺乳动物一样，多巴胺受体激动剂的应用对这些神经元的兴奋性有差异调节作用，增加了表达 D1 的神经元的兴奋性，降低了表达 D2 的神经元的兴奋性。我们的研究结果表明，D1 和 D2 受体在直接和间接纹状体投射神经元中的分离表达在整个脊椎动物门中得到了保守。由于多巴胺受体激动剂对这些通路有差异调节作用，增加了直接通路的兴奋性，降低了间接通路的兴奋性，这种组织可能作为一种偏向于动作选择的机制得到了保守。
