Dopamine D1 Receptor-Mediated Transmission Maintains Information Flow Through the Cortico-Striato-Entopeduncular Direct Pathway to Release Movements.
Dopamine D1 Receptor-Mediated Transmission Maintains Information Flow Through the Cortico-Striato-Entopeduncular Direct Pathway to Release Movements.
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DOI：
10.1093/cercor/bhv209
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发表时间：
2015-12
期刊：
影响因子：
--
通讯作者：
Nambu A
中科院分区：
文献类型：
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作者：
Chiken S;Sato A;Ohta C;Kurokawa M;Arai S;Maeshima J;Sunayama-Morita T;Sasaoka T;Nambu A
在基底神经节 (BG) 中，多巴胺在运动控制中发挥着关键作用，多巴胺缺乏会导致严重的运动功能障碍，如帕金森病。根据公认的 BG 模型，多巴胺激活纹状体直接通路神经元，通过 D1 受体（D1R）直接投射到 BG 的输出核，而多巴胺抑制纹状体间接通路神经元，通过 D2 受体投射到外部苍白球（GPe）。为了阐明体内 D1R 多巴胺能传递的确切作用，我们开发了新型 D1R 敲低小鼠，其中 D1R 可以受到条件性和可逆性调节。通过强力霉素治疗抑制 D1R 表达会降低小鼠的自发运动活动并损害运动能力。在清醒条件下记录内脚核（EPN）（啮齿动物 BG 的输出核之一）的神经元活动，以检查运动缺陷的机制。在 D1R 表达抑制过程中，由皮质-纹状体-EPN 直接通路介导的 EPN 皮质诱发抑制大部分消失，而自发放电率和模式保持不变。另一方面，GPe 活性变化不大。这些结果表明，D1R 介导的多巴胺能传递维持通过直接途径的信息流，以适当地释放运动动作。
In the basal ganglia (BG), dopamine plays a pivotal role in motor control, and dopamine deficiency results in severe motor dysfunctions as seen in Parkinson's disease. According to the well-accepted model of the BG, dopamine activates striatal direct pathway neurons that directly project to the output nuclei of the BG through D1 receptors (D1Rs), whereas dopamine inhibits striatal indirect pathway neurons that project to the external pallidum (GPe) through D2 receptors. To clarify the exact role of dopaminergic transmission via D1Rs in vivo, we developed novel D1R knockdown mice in which D1Rs can be conditionally and reversibly regulated. Suppression of D1R expression by doxycycline treatment decreased spontaneous motor activity and impaired motor ability in the mice. Neuronal activity in the entopeduncular nucleus (EPN), one of the output nuclei of the rodent BG, was recorded in awake conditions to examine the mechanism of motor deficits. Cortically evoked inhibition in the EPN mediated by the cortico-striato-EPN direct pathway was mostly lost during suppression of D1R expression, whereas spontaneous firing rates and patterns remained unchanged. On the other hand, GPe activity changed little. These results suggest that D1R-mediated dopaminergic transmission maintains the information flow through the direct pathway to appropriately release motor actions.