Xiao Lei, Priest Michael F, Nasenbeny Jordan, Lu Ting, Kozorovitskiy Yevgenia
Department of Neurobiology, Northwestern University, Evanston, IL 60208, USA.
Roxelyn and Richard Pepper Department of Communication Sciences and Disorders, Northwestern University, Evanston, IL 60208, USA.
Neuron. 2017 Jul 19;95(2):368-384.e5. doi: 10.1016/j.neuron.2017.06.003. Epub 2017 Jun 29.
The release of dopamine (DA) regulates rewarding behavior and motor actions through striatum-targeting efferents from ventral tegmental area (VTA) and substantia nigra pars compacta (SNc). Here, we map and functionally characterize axonal projections from oxytocin neurons in the hypothalamic paraventricular nucleus to midbrain DA regions. Electrophysiological recordings of DA neurons reveal that both the application of oxytocin and optogenetic stimulation of oxytocinergic terminals suffice to increase DA neuron activity in the VTA but downregulate it in SNc. This biased modulation is mediated by oxytocin and vasopressin G-protein-coupled receptors. Oxytocin release directly activates DA neurons and indirectly inhibits them through local GABA neurons, but the relative magnitudes of the two mechanisms differ in VTA and SNc. Oxytocin-modulated DA neurons give rise to canonical striatal projections. Since hypothalamic oxytocinergic projections also target the striatum, oxytocin is poised to bias the balance of DA tone through multiple sites in vertebrate reward circuits.
多巴胺（DA）的释放通过腹侧被盖区（VTA）和黑质致密部（SNc）向纹状体的传出纤维调节奖赏行为和运动动作。在此，我们绘制了下丘脑室旁核中催产素神经元到中脑多巴胺区域的轴突投射图，并对其进行了功能表征。多巴胺能神经元的电生理记录显示，应用催产素和对催产素能终末进行光遗传学刺激均足以增加VTA中多巴胺能神经元的活性，但会下调SNc中多巴胺能神经元的活性。这种偏向性调节由催产素和血管加压素G蛋白偶联受体介导。催产素释放直接激活多巴胺能神经元，并通过局部GABA能神经元间接抑制它们，但这两种机制的相对强度在VTA和SNc中有所不同。受催产素调节的多巴胺能神经元产生典型的纹状体投射。由于下丘脑催产素能投射也靶向纹状体，因此催产素可能会通过脊椎动物奖赏回路中的多个位点来偏向多巴胺张力的平衡。
