Choi Ji-Kyung, Chen Y Iris, Hamel Edith, Jenkins Bruce G
MGH-NMR Center and Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Building 149 13th Street Charlestown, MA 02129, USA.
Neuroimage. 2006 Apr 15;30(3):700-12. doi: 10.1016/j.neuroimage.2005.10.029. Epub 2006 Feb 3.
The coupling between neurotransmitter-induced changes in neuronal activity and the resultant hemodynamic response is central to the interpretation of neuroimaging techniques. In the present study, MRI experiments showed that dopamine transporter blockers such as cocaine and dopamine releasers such as amphetamine and D1 receptor agonists induced large positive increases in relative cerebral blood volume (rCBV) that were not sensitive to nitric oxide synthase inhibition. However, D1/D5 receptor antagonism with SCH-23390 prevented or blocked the hemodynamic response without any concomitant effect on dopamine release. Dopamine D2/D3 receptor agonists, in contrast, induced negative changes in rCBV in brain regions corresponding largely to those endowed with these receptors. D1 and D5 receptor mRNAs were expressed in microvessels of responsive brain areas, while D2 and D3 receptors were not consistently associated with the microvascular bed. D3 receptors had an astroglial localization. Together, these experiments show that direct effects of dopamine upon the vasculature cannot be ignored in measuring the hemodynamic coupling associated with dopaminergic drugs. These results further suggest that this coupling is partially mediated through D1/D5 receptors on the microvasculature leading to increased rCBV and through astroglial D3 receptors leading to decreased rCBV. These data provide additional support for the role of local post-synaptic events in neurovascular coupling and emphasize that the interpretation of fMRI signals exclusively in terms of neuronal activity may be incomplete.
神经递质诱导的神经元活动变化与由此产生的血液动力学反应之间的耦合对于神经成像技术的解释至关重要。在本研究中，MRI实验表明，可卡因等多巴胺转运体阻滞剂以及苯丙胺和D1受体激动剂等多巴胺释放剂可诱导相对脑血容量（rCBV）大幅正向增加，且这种增加对一氧化氮合酶抑制不敏感。然而，用SCH-23390进行D1/D5受体拮抗可预防或阻断血液动力学反应，而对多巴胺释放没有任何伴随影响。相比之下，多巴胺D2/D3受体激动剂在很大程度上对应于那些具有这些受体的脑区中诱导rCBV出现负向变化。D1和D5受体mRNA在反应性脑区的微血管中表达，而D2和D3受体与微血管床并无始终一致的关联。D3受体定位于星形胶质细胞。总之，这些实验表明，在测量与多巴胺能药物相关的血液动力学耦合时，多巴胺对脉管系统的直接作用不容忽视。这些结果进一步表明，这种耦合部分是通过微血管上的D1/D5受体介导，导致rCBV增加，以及通过星形胶质细胞D3受体介导，导致rCBV降低。这些数据为局部突触后事件在神经血管耦合中的作用提供了额外支持，并强调仅根据神经元活动来解释功能磁共振成像信号可能并不完整。
