Zhao Bo, Zhu Junling, Dai Dongqing, Xing Junling, He Jiahou, Fu Zhanyan, Zhang Lei, Li Zhuyi, Wang Wenting
Department of Neurology, Tangdu Hospital, Fourth Military Medical University, Xi'an 710038, PR China; Department of Neurobiology and Collaborative Innovation Center for Brain Science, School of Basic Medicine, Fourth Military Medical University, Xi'an 710032, PR China; Department of Neurology, Anning Branch of Lanzhou General Hospital of Lanzhou Military Region, Lanzhou 730070, PR China.
Department of Neurosurgery, Tangdu Hospital, Fourth Military Medical University, Xi'an 710038, PR China.
Neuropharmacology. 2016 Aug;107:396-410. doi: 10.1016/j.neuropharm.2016.03.037. Epub 2016 Mar 24.
The dorsal striatum plays a key role in motor control and cognitive processes. Proper functioning of the striatum relies on the fine dynamic balance between the direct pathway projection medium spiny neurons (MSNs) that express D1 dopamine receptor (D1 MSNs) and indirect pathway projection MSNs that express D2 dopamine receptor (D2 MSNs). The inwardly rectifying K(+) channels (Kir), which express on both D1 and D2 MSNs, participate in the subthreshold dynamics including the membrane resonance and dendritic integration. However, it remains unclear whether dopamine differentially regulates Kir mediated subthreshold dynamics in two subtypes MSNs. Using transgenic mice that express either tdTomato in D1 MSNs or eGFP in D2 MSNs, we explored the Kir mediated subthreshold dynamics in D1 or D2 MSNs with whole cell patch clamp recording in acute brain slices. We found that D1 receptor agonist increased the Kir current while D2 receptor activation decreased the Kir conductance. The dopamine regulation of the Kir enhanced the resonant frequency and reduced the resonant impedance of D1 MSNs. The converse is ture for D2 MSNs. It also caused an opposing effect on dendritic integration between D1 and D2 MSNs, which can promote stability of the two pathways. The D1 receptor activation modulated Kir through cAMP-PKA signaling, whereas the D2 receptor modulated Kir through PLC-PKC signaling. Our findings demonstrated the differential dopaminergic regulation role of Kir, which mediates distinct subthreshold dynamics, and thus, contributes to the role of dopamine in fine tuning the balance of the striatal direct and indirect pathway activities.
背侧纹状体在运动控制和认知过程中起关键作用。纹状体的正常功能依赖于表达D1多巴胺受体的直接通路投射中型多棘神经元（MSNs，即D1 MSNs）和表达D2多巴胺受体的间接通路投射MSNs之间精确的动态平衡。内向整流钾通道（Kir）在D1和D2 MSNs上均有表达，参与阈下动力学过程，包括膜共振和树突整合。然而，多巴胺是否对两种亚型MSNs中Kir介导的阈下动力学有不同调节作用仍不清楚。利用在D1 MSNs中表达tdTomato或在D2 MSNs中表达eGFP的转基因小鼠，我们在急性脑片中采用全细胞膜片钳记录技术探究了D1或D2 MSNs中Kir介导的阈下动力学。我们发现D1受体激动剂增加了Kir电流，而D2受体激活则降低了Kir电导。多巴胺对Kir的调节增强了D1 MSNs的共振频率并降低了其共振阻抗。D2 MSNs的情况则相反。它还对D1和D2 MSNs之间的树突整合产生相反的影响，这可促进两条通路的稳定性。D1受体激活通过cAMP-PKA信号通路调节Kir，而D2受体通过PLC-PKC信号通路调节Kir。我们的研究结果证明了Kir的多巴胺能差异调节作用，其介导了不同的阈下动力学，因此有助于多巴胺在微调纹状体直接和间接通路活动平衡中的作用。
