Plasticity in striatal dopamine release is governed by release-independent depression and the dopamine transporter
Plasticity in striatal dopamine release is governed by release-independent depression and the dopamine transporter
复制标题
DOI：
10.1038/s41467-019-12264-9
复制
发表时间：
2019-09-19
影响因子：
16.6
通讯作者：
Cragg, Stephanie J.
中科院分区：
文献类型：
--
作者：
Condon, Mark D.;Platt, Nicola J.;Cragg, Stephanie J.
中纹状体多巴胺能神经元具有广泛的分支轴突乔木。动作电位是否在纹状体中转化为多巴胺输出将受到轴突特性和机制的动态和关键影响，这些特性和机制知之甚少。在这里，我们解决的作用，在确定短期可塑性的多巴胺释放的释放概率和轴突活性的机制，使用快速扫描循环伏安法在离体小鼠纹状体。我们发现，短暂的短期促进和较长的短期抑郁症是只有弱依赖于初始释放的水平，即释放不敏感。相反，短期可塑性是强烈决定的机制，管理轴突激活，包括K+门控兴奋性和多巴胺转运蛋白，特别是在背侧纹状体。我们确定多巴胺转运蛋白作为多巴胺短期可塑性的主要调节剂，控制释放依赖性和独立机制之间的平衡，也显示区域特异性门控。
Mesostriatal dopaminergic neurons possess extensively branched axonal arbours. Whether action potentials are converted to dopamine output in the striatum will be influenced dynamically and critically by axonal properties and mechanisms that are poorly understood. Here, we address the roles for mechanisms governing release probability and axonal activity in determining short-term plasticity of dopamine release, using fast-scan cyclic voltammetry in the ex vivo mouse striatum. We show that brief short-term facilitation and longer short term depression are only weakly dependent on the level of initial release, i.e. are release insensitive. Rather, short-term plasticity is strongly determined by mechanisms which govern axonal activation, including K+-gated excitability and the dopamine transporter, particularly in the dorsal striatum. We identify the dopamine transporter as a master regulator of dopamine short-term plasticity, governing the balance between release-dependent and independent mechanisms that also show region-specific gating.