RIKEN Brain Science Institute, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan.
Proc Natl Acad Sci U S A. 2013 Aug 27;110(35):14124-31. doi: 10.1073/pnas.1312804110. Epub 2013 Aug 2.
We investigated a unique microzone of the cerebellum located in folium-p (fp) of rabbit flocculus. In fp, Purkinje cells were potently excited by stimulation of the hypothalamus or mesencephalic periaqueductal gray, which induced defense reactions. Using multiple neuroscience techniques, we determined that this excitation was mediated via beaded axons of orexinergic hypothalamic neurons passing collaterals through the mesencephalic periaqueductal gray. Axonal tracing studies using DiI and biotinylated dextran amine evidenced the projection of fp Purkinje cells to the ventrolateral corner of the ipsilateral parabrachial nucleus (PBN). Because, in defense reactions, arterial blood flow has been known to redistribute from visceral organs to active muscles, we hypothesized that, via PBN, fp adaptively controls arterial blood flow redistribution under orexin-mediated neuromodulation that could occur in defense behavior. This hypothesis was supported by our finding that climbing fiber signals to fp Purkinje cells were elicited by stimulation of the aortic nerve, a high arterial blood pressure, or a high potassium concentration in muscles, all implying errors in the control of arterial blood flow. We further examined the arterial blood flow redistribution elicited by electric foot shock stimuli in awake, behaving rabbits. We found that systemic administration of an orexin antagonist attenuated the redistribution and that lesioning of fp caused an imbalance in the redistribution between active muscles and visceral organs. Lesioning of fp also diminished foot shock-induced increases in the mean arterial blood pressure. These results collectively support the hypothesis that the fp microcomplex adaptively controls defense reactions under orexin-mediated neuromodulation.
我们研究了位于兔绒小球叶(fp)中的小脑的一个独特微区。在 fp 中，刺激下丘脑或中脑导水管周围灰质可强烈兴奋浦肯野细胞，引起防御反应。使用多种神经科学技术，我们确定这种兴奋是通过下丘脑的食欲素能神经元的珠状轴突传递，这些神经元通过侧脑导水管周围灰质的侧支传递。使用 DiI 和生物素化葡聚糖胺进行的轴突追踪研究表明，fp 浦肯野细胞投射到同侧臂旁核（PBN）的腹外侧角。因为在防御反应中，动脉血流已经知道从内脏器官重新分配到活跃的肌肉，所以我们假设通过 PBN，fp 在食欲素介导的神经调节下自适应地控制动脉血流重新分配，这种调节可能发生在防御行为中。我们的发现支持了这一假设，即刺激主动脉神经、高动脉血压或肌肉中高钾浓度可引起 fp 浦肯野细胞的 climbing 纤维信号，这都意味着动脉血流控制出现错误。我们进一步研究了清醒、行为活跃的兔子中电脚刺激引起的动脉血流重新分配。我们发现，全身给予食欲素拮抗剂可减弱这种重新分配，而 fp 损伤会导致活跃肌肉和内脏器官之间的重新分配失衡。fp 损伤还会降低脚震引起的平均动脉血压升高。这些结果共同支持了 fp 微复合体在食欲素介导的神经调节下自适应地控制防御反应的假说。
