Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand.
J Neurochem. 2022 Sep;162(5):417-429. doi: 10.1111/jnc.15677. Epub 2022 Aug 4.
A distinct population of dopamine neurons in the substantia nigra pars lateralis (SNL) has a unique projection to the most caudolateral (tail) region of the striatum. Here, using two electrochemical techniques to measure basal dopamine and electrically evoked dopamine release in anesthetized rats, we characterized this pathway, and compared it with the 'classic' nigrostriatal pathway from neighboring substantia nigra pars compacta (SNc) dopamine neurons to the dorsolateral striatum. We found that the tail striatum constitutes a distinct dopamine domain compared with the dorsolateral striatum, with consistently lower basal and evoked dopamine, and diverse dopamine release kinetics. Importantly, electrical stimulation of the SNL and SNc evoked dopamine release in entirely separate striatal regions; the tail and dorsolateral striatum, respectively. Furthermore, we showed that stimulation of the subthalamic nucleus (STN) evoked dopamine release exclusively in the tail striatum, likely via the SNL, consistent with previous anatomical evidence of STN afferents to SNL dopamine neurons. Our work identifies the STN as an important modulator of dopamine release in a novel dopamine pathway to the tail striatum, largely independent of the classic nigrostriatal pathway, which necessitates a revision of the basal ganglia circuitry with the STN positioned as a central integrator of striatal information.
侧部黑质（SNL）中的多巴胺神经元有一个独特的群体，它们投射到纹状体最尾侧（尾部）区域。在这里，我们使用两种电化学技术来测量麻醉大鼠中的基础多巴胺和电诱发多巴胺释放，从而对这条通路进行了表征，并将其与来自相邻致密部黑质（SNc）多巴胺神经元的“经典”黑质纹状体通路进行了比较，后者投射到背外侧纹状体。我们发现，与背外侧纹状体相比，尾部纹状体构成了一个独特的多巴胺区域，其基础和诱发多巴胺水平始终较低，多巴胺释放动力学也不同。重要的是，SNL 和 SNc 的电刺激在完全不同的纹状体区域引发多巴胺释放；分别是尾部和背外侧纹状体。此外，我们还表明，苍白球内侧核（STN）的刺激仅在尾部纹状体中引发多巴胺释放，这可能是通过 SNL 实现的，与 STN 传入 SNL 多巴胺神经元的先前解剖学证据一致。我们的工作确定了 STN 作为一种新型尾部纹状体多巴胺通路中多巴胺释放的重要调节剂，其与经典黑质纹状体通路在很大程度上是独立的，这需要对基底节回路进行修订，将 STN 定位为纹状体信息的中央整合器。
