title: Differential dopaminergic regulation of inwardly rectifying potassium channel mediated subthreshold dynamics in striatal medium spiny neurons.
abstract: 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.
authors.affiliation: 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.
authors.forename: Bo
authors.initials: B
authors.lastname: Zhao
authors.affiliation: Department of Neurosurgery, Tangdu Hospital, Fourth Military Medical University, Xi'an 710038, PR China.
authors.forename: Junling
authors.initials: J
authors.lastname: Zhu
authors.affiliation: Department of Neurobiology and Collaborative Innovation Center for Brain Science, School of Basic Medicine, Fourth Military Medical University, Xi'an 710032, PR China; Cadet Brigade, Fourth Military Medical University, Xi'an 710032, PR China.
authors.forename: Dongqing
authors.initials: D
authors.lastname: Dai
authors.affiliation: Department of Neurobiology and Collaborative Innovation Center for Brain Science, School of Basic Medicine, Fourth Military Medical University, Xi'an 710032, PR China.
authors.forename: Junling
authors.initials: J
authors.lastname: Xing
authors.affiliation: Department of Neurobiology and Collaborative Innovation Center for Brain Science, School of Basic Medicine, Fourth Military Medical University, Xi'an 710032, PR China; Cadet Brigade, Fourth Military Medical University, Xi'an 710032, PR China.
authors.forename: Jiahou
authors.initials: J
authors.lastname: He
authors.affiliation: Model System and Neurobiology Department, Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
authors.forename: Zhanyan
authors.initials: Z
authors.lastname: Fu
authors.affiliation: Department of Neurosurgery, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, PR China.
authors.forename: Lei
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Neurology, Tangdu Hospital, Fourth Military Medical University, Xi'an 710038, PR China. Electronic address: lizhuyi@fmmu.edu.cn.
authors.forename: Zhuyi
authors.initials: Z
authors.lastname: Li
authors.affiliation: Department of Neurobiology and Collaborative Innovation Center for Brain Science, School of Basic Medicine, Fourth Military Medical University, Xi'an 710032, PR China. Electronic address: wwt0657@fmmu.edu.cn.
authors.forename: Wenting
authors.initials: W
authors.lastname: Wang
mesh_terms: D000818:Animals; D003342:Corpus Striatum / Q000378:metabolism*; D065127:Dopamine D2 Receptor Antagonists / Q000494:pharmacology; D059290:Dopaminergic Neurons / Q000378:metabolism*; D005260:Female; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009924:Organ Culture Techniques; D024661:Potassium Channels, Inwardly Rectifying / Q000502:physiology*; D017447:Receptors, Dopamine D1 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D017448:Receptors, Dopamine D2 / Q000378:metabolism*
chemical_list: D065127:Dopamine D2 Receptor Antagonists; D024661:Potassium Channels, Inwardly Rectifying; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2
keywords: Dendritic integration; Dopamine receptor; Dorsal striatum; Medium-sized spiny neurons; Membrane resonance; Patch clamp