Department of Physiology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA.
Department of Physiology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA.
Neuron. 2020 Apr 22;106(2):277-290.e6. doi: 10.1016/j.neuron.2020.01.028. Epub 2020 Feb 18.
Substantia nigra dopamine neurons have been implicated in the initiation and invigoration of movement, presumably through their modulation of striatal projection neuron (SPN) activity. However, the impact of native dopaminergic transmission on SPN excitability has not been directly demonstrated. Using perforated patch-clamp recording, we found that optogenetic stimulation of nigrostriatal dopamine axons rapidly and persistently elevated the excitability of D1 receptor-expressing SPNs (D1-SPNs). The evoked firing of D1-SPNs increased within hundreds of milliseconds of stimulation and remained elevated for ≥ 10 min. Consistent with the negative modulation of depolarization- and Ca-activated K currents, dopaminergic transmission accelerated subthreshold depolarization in response to current injection, reduced the latency to fire, and transiently diminished action potential afterhyperpolarization. Persistent modulation was protein kinase A dependent and associated with a reduction in action potential threshold. Together, these data demonstrate that dopaminergic transmission potently increases D1-SPN excitability with a time course that could support subsecond and sustained behavioral control.
黑质多巴胺能神经元被认为参与了运动的发起和活跃，可能是通过调节纹状体投射神经元（SPN）的活性。然而，内源性多巴胺能传递对 SPN 兴奋性的影响尚未被直接证明。使用穿孔膜片钳记录，我们发现黑质纹状体多巴胺轴突的光遗传学刺激可快速且持续地提高 D1 受体表达的 SPN（D1-SPN）的兴奋性。刺激后数百毫秒内，D1-SPN 的诱发放电增加，并持续升高≥10 分钟。与去极化和 Ca 激活的 K 电流的负调节一致，多巴胺能传递加速了对电流注入的亚阈值去极化，减少了放电潜伏期，并短暂地减小了动作电位后超极化。持续的调制依赖于蛋白激酶 A，与动作电位阈值的降低有关。综上所述，这些数据表明，多巴胺能传递可强烈增加 D1-SPN 的兴奋性，其时间过程可支持亚秒级和持续的行为控制。
