Differential dopaminergic regulation of inwardly rectifying potassium channel mediated subthreshold dynamics in striatal medium spiny neurons
Differential dopaminergic regulation of inwardly rectifying potassium channel mediated subthreshold dynamics in striatal medium spiny neurons
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纹状体中棘神经元内向整流钾通道介导的阈下动力学的差异多巴胺能调节
DOI：
10.1016/j.neuropharm.2016.03.037
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发表时间：
2016-08
影响因子：
4.7
通讯作者：
Wang Wenting
中科院分区：
文献类型：
--
作者：
Zhao Bo;Zhu Junling;Dai Dongqing;Xing Junling;He Jiahou;Fu Zhanyan;Zhang Lei;Li Zhuyi;Wang Wenting
背侧纹状体在运动控制和认知过程中起着关键作用。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媒介棘神经元(D1MSN)和表达D2多巴胺受体的间接通路投射MSN(D2MSN)之间的良好动态平衡。内向整流性K+通道(KIR)在D1MSN和D2MSN上均有表达，参与了膜共振和树突整合等阈值下动力学过程。然而，目前尚不清楚多巴胺是否对KIR介导的两种亚型MSN的阈值下动力学有不同的调节作用。利用在D1MSN中表达tdTomato或在D2MSN中表达EGFP的转基因小鼠，在急性脑片上用全细胞膜片钳记录技术研究KIR介导的D1MSN和D2MSN的阈值下动力学。我们发现，D2受体激动剂使KIR电流增加，而D2受体激动剂使KIR电导降低。多巴胺对KIR的调节提高了D1MSN的共振频率，降低了共振阻抗。反之亦然，对于D2 MSN。它还对D1MSN和D2MSN之间的树枝状整合产生相反的影响，从而促进了这两条途径的稳定性。D1受体通过cAMP-PKA信号调节KIR，而D2受体通过PLC-PKC信号调节KIR。我们的发现证明了KIR的不同的多巴胺能调节作用，它介导了不同的阈值下动力学，从而有助于多巴胺在微调纹状体直接和间接通路活动的平衡中的作用。
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.
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影响因子：
64.8
作者：
Hansen, Scott B.;Tao, Xiao;MacKinnon, Roderick
通讯作者：
MacKinnon, Roderick
影响因子：
25
作者：
Tong, Xiaoping;Ao, Yan;Faas, Guido C.;Nwaobi, Sinifunanya E.;Xu, Ji;Haustein, Martin D.;Anderson, Mark A.;Mody, Istvan;Olsen, Michelle L.;Sofroniew, Michael V.;Khakh, Baljit S.
通讯作者：
Khakh, Baljit S.
影响因子：
6.1
作者：
Sciamanna G;Bonsi P;Tassone A;Cuomo D;Tscherter A;Viscomi MT;Martella G;Sharma N;Bernardi G;Standaert DG;Pisani A
通讯作者：
Pisani A
DOI：
10.1073/pnas.1107748108
发表时间：
2011-07-12
影响因子：
11.1
作者：
McCarthy, M. M.;Moore-Kochlacs, C.;Kopell, N.
通讯作者：
Kopell, N.
影响因子：
2.5
作者：
Pape, HC;Driesang, RB
通讯作者：
Driesang, RB