Optogenetic Stimulation of Frontal D1 Neurons Compensates for Impaired Temporal Control of Action in Dopamine-Depleted Mice.
Optogenetic Stimulation of Frontal D1 Neurons Compensates for Impaired Temporal Control of Action in Dopamine-Depleted Mice.
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DOI：
10.1016/j.cub.2016.11.029
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发表时间：
2017-01-09
期刊：
影响因子：
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通讯作者：
Narayanan NS
中科院分区：
文献类型：
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作者：
Kim YC;Han SW;Alberico SL;Ruggiero RN;De Corte B;Chen KH;Narayanan NS
中皮层多巴胺紊乱与帕金森病（PD）的认知症状有关。过去的研究表明，内侧额叶神经元表达D1多巴胺受体（D1DRs）参与时间加工。在这里，我们研究这些神经元是否可以补偿中脑多巴胺功能障碍导致的行为缺陷。我们报告三个主要结果。首先，PD患者和腹侧被盖区（VTA）多巴胺缺失的小鼠在间隔时间内内侧额叶皮质（MFC）的δ活动（1-4 Hz）减弱。其次，我们发现光遗传学刺激MFC D1DR神经元可以增加MFC神经元之间的斜坡活动。最后，以δ频率（2hz）特异性刺激MFC D1DR神经元，弥补了VTA多巴胺耗竭引起的时间控制动作的缺陷。我们的研究结果表明，皮层网络可以通过特定频率的大脑刺激来改善多巴胺依赖的认知处理。Kim等人研究了初级认知加工过程中内侧额叶皮层的神经网络。他们发现，人类和啮齿动物的额叶三角洲节律都依赖于多巴胺。刺激表达d1型多巴胺受体的额叶神经元可改善颞叶加工，2 Hz刺激额叶神经元可改善动作的颞叶控制。
Disrupted mesocortical dopamine contributes to cognitive symptoms of Parkinson’s disease (PD). Past work has implicated medial frontal neurons expressing D1 dopamine receptors (D1DRs) in temporal processing. Here, we investigate if these neurons can compensate for behavioral deficits resulting from midbrain dopamine dysfunction. We report three main results. First, both PD patients and mice with ventral tegmental area (VTA) dopamine depletion had attenuated delta activity (1–4 Hz) in the medial frontal cortex (MFC) during interval timing. Second, we found that optogenetically stimulating MFC D1DR neurons could increase ramping activity among MFC neurons. Finally, stimulating MFC D1DR neurons specifically at delta frequencies (2 Hz) compensated for deficits in temporal control of action caused by VTA dopamine depletion. Our results suggest that cortical networks can be targeted by frequency-specific brain stimulation to improve dopamine-dependent cognitive processing. Kim et al., study neuronal networks in medial frontal cortex during elementary cognitive processing. They find that frontal delta rhythms depend on dopamine in both humans and rodents. Stimulating frontal neurons expressing D1-type dopamine receptors improves temporal processing and stimulating frontal neurons at 2 Hz can improve the temporal control of action.