Functional Dissection of Basal Ganglia Inhibitory Inputs onto Substantia Nigra Dopaminergic Neurons.

Functional Dissection of Basal Ganglia Inhibitory Inputs onto Substantia Nigra Dopaminergic Neurons.
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基底神经节抑制输入对黑质多巴胺能神经元的功能剖析。

DOI:
10.1016/j.celrep.2020.108156
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发表时间:
2020-09-15
期刊:
影响因子:
8.8
通讯作者:
Khaliq, Zayd M.
Khaliq, Zayd M.
中科院分区:
生物学1区
文献类型:
--
作者:
Evans, Rebekah C.;Twedell, Emily L.;Zhu, Manhua;Ascencio, Jefferson;Zhang, Renshu;Khaliq, Zayd M.

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黑质(SNC)多巴胺能神经元对厌恶刺激的反应是放电抑制暂停,然后是短暂的反弹激活。我们测试了来自背侧纹状体(纹状体和基质)和苍白球外区(GPE;小白蛋白和Lhx6阳性)的遗传群体的抑制性突触输入到SNC神经元的整合,并检查了它们对暂停反弹放电的贡献。以网状部(SNR)中的“树突束”为靶标的纹状体投射的激活,持续地静默放电,并从纹状体抑制中解脱,触发反弹活动。星形体抑制性突触后电流是GABA-B受体介导的一个重要成分,它加强了SNR树突突触对躯体兴奋性的影响,并使其能够反弹。相比之下,GPE投射激活了胞体和近端树突上的GABA-A受体,但不会导致反弹。最后,光学标测显示,背侧纹状体选择性地抑制腹侧的黑质神经元群,这些神经元本质上具有反弹的能力。因此,我们定义了一个独特的纹状体黑质回路来产生多巴胺反弹。埃文斯等人。从功能上将抑制输入映射到来自遗传定义的基底节亚群的SNC多巴胺神经元树突上。使用双光子钙成像和计算模型,他们揭示了树突特有的纹状体黑质回路,促进了多巴胺神经元的反弹活动。
Substantia nigra (SNc) dopaminergic neurons respond to aversive stimuli with inhibitory pauses in firing followed by transient rebound activation. We tested integration of inhibitory synaptic inputs onto SNc neurons from genetically defined populations in dorsal striatum (striosome and matrix) and external globus pallidus (GPe; parvalbumin- and Lhx6-positive), and examined their contribution to pause-rebound firing. Activation of striosome projections, which target “dendron bouquets” in the pars reticulata (SNr), consistently quiets firing and relief from striosome inhibition triggers rebound activity. Striosomal inhibitory postsynaptic currents (IPSCs) display a prominent GABA-B receptor-mediated component that strengthens the impact of SNr dendrite synapses on somatic excitability and enables rebounding. By contrast, GPe projections activate GABA-A receptors on the soma and proximal dendrites but do not result in rebounding. Lastly, optical mapping shows that dorsal striatum selectively inhibits the ventral population of SNc neurons, which are intrinsically capable of rebounding. Therefore, we define a distinct striatonigral circuit for generating dopamine rebound. Evans et al. functionally map inhibitory inputs onto SNc dopamine neuron dendrites from genetically defined basal ganglia subpopulations. Using two-photon calcium imaging and computational modeling, they reveal a dendrite-specific striatonigral circuit that facilitates dopamine neuron rebound activity.
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