Department of Physiology and Pharmacology, Oregon Health and Science University, Portland, Oregon 97223, USA.
Synapse. 2013 Feb;67(2):94-108. doi: 10.1002/syn.21624. Epub 2012 Nov 28.
The periaqueductal gray (PAG) is a critical brain region involved in opioid analgesia and provides efferents to descending pathways that modulate nociception. In addition, the PAG contains ascending pathways to regions involved in the regulation of reward, including the substantia nigra (SN) and the ventral tegmental area (VTA). SN and VTA contain dopaminergic neurons that are critical for the maintenance of positive reinforcement. Interestingly, the PAG is also reported to contain a population of dopaminergic neurons. In this study, the distribution of catecholaminergic neurons within the ventrolateral (vl) PAG was examined using immunocytochemical methods. In addition, the catecholaminergic PAG neurons were examined to determine whether these neurons are integrated into ascending (VTA, SN) and descending rostral ventral medulla (RVM) efferent pathways from this region. The immunocytochemical analysis determined that catecholaminergic neurons in the PAG are both dopaminergic and noradrenergic and these neurons have a distinct rostrocaudal distribution within the ventrolateral column of PAG. Dopaminergic neurons were concentrated rostrally and were significantly smaller than noradrenergic neurons. Combined immunocytochemistry and tract tracing methods revealed that catecholaminergic neurons are distinct from, but closely associated with, both ascending and descending efferent projection neurons. Finally, by electron microscopy, catecholaminergic neurons showed close dendritic appositions with other neurons in PAG, suggesting a possible nonsynaptic mechanism for regulation of PAG output by these neurons. In conclusion, our data indicate that there are two populations of catecholaminergic neurons in the vlPAG that form dendritic associations with both ascending and descending efferents suggesting a possible nonsynaptic modulation of vlPAG neurons.
导水管周围灰质（periaqueductal gray，PAG）是参与阿片类药物镇痛的关键脑区，它为调节伤害感受的下行通路提供传出纤维。此外，PAG 包含上行通路到参与奖赏调节的区域，包括黑质（substantia nigra，SN）和腹侧被盖区（ventral tegmental area，VTA）。SN 和 VTA 包含多巴胺能神经元，这些神经元对维持正强化至关重要。有趣的是，PAG 也被报道包含一群多巴胺能神经元。在这项研究中，使用免疫细胞化学方法检查了腹外侧（ventrolateral，vl）PAG 内儿茶酚胺能神经元的分布。此外，还检查了儿茶酚胺能 PAG 神经元，以确定这些神经元是否整合到来自该区域的上行（VTA、SN）和下行延髓头端腹内侧（rostral ventral medulla，RVM）传出通路中。免疫细胞化学分析确定 PAG 中的儿茶酚胺能神经元既是多巴胺能神经元又是去甲肾上腺素能神经元，并且这些神经元在 PAG 的腹外侧柱中有明显的头尾分布。多巴胺能神经元集中在头部，明显小于去甲肾上腺素能神经元。联合免疫细胞化学和追踪方法显示，儿茶酚胺能神经元与上行和下行传出投射神经元不同，但密切相关。最后，通过电子显微镜，儿茶酚胺能神经元与 PAG 中的其他神经元有密切的树突接触，表明这些神经元可能通过非突触机制调节 PAG 的输出。总之，我们的数据表明，vlPAG 中有两种儿茶酚胺能神经元群体，它们与上行和下行传出纤维形成树突联系，这表明 vlPAG 神经元可能存在非突触调节。
