Genetically expressed transneuronal tracer reveals direct and indirect serotonergic descending control circuits
Genetically expressed transneuronal tracer reveals direct and indirect serotonergic descending control circuits
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DOI：
10.1002/cne.21665
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发表时间：
2008-04-20
影响因子：
2.5
通讯作者：
Basbaum, Allan I.
中科院分区：
文献类型：
--
作者：
Braz, Joao Manuel;Basbaum, Allan I.
尽管有证据表明，一个显着的贡献，脑干多巴胺能（5 HT）系统的控制脊髓“疼痛”的传递神经元，注意力最近转向非多巴胺能神经元的影响，包括易化和抑制性控制，起源于所谓的“上”和“关”细胞的rostroventral延髓（RVM）。然而，不清楚的是，后者的电路相互作用的程度，或受多巴胺能细胞群。为了解决这个问题，我们选择性地有针对性地表达的transneuronal示踪剂，麦胚凝集素（WGA），在5 HT神经元，以研究5 HT和非5 HT系统之间的相互作用。除了证实直接向脊髓的髓5 HT投射外，我们还观察到在髓网状核的网状细胞和大细胞中有大量的非5 HT神经元，它们是WGA免疫反应性的，即，从5 HT神经元经神经元标记。将FluoroGold注射到脊髓中证实，这些网状神经元不仅与髓质的5 HT神经元突触后，而且大多数也位于下行球脊髓通路的起源处。相比之下，我们没有发现证据表明中脑导水管周围灰质的神经元投射到RVM是中脑或延髓5 HT神经元的突触后。最后，我们发现很少的例子WGA免疫反应性去甲肾上腺素能神经元，这表明有相当大的独立性的单胺能延髓脊髓通路。我们的研究结果表明，5-HT神经元直接和间接地影响“疼痛”的处理在脊髓水平通过前馈连接与多个非5-HT下行控制通路。
Despite the evidence for a significant contribution of brainstem serotonergic (5HT) systems to the control of spinal cord "pain" transmission neurons, attention has turned recently to the influence of nonserotonergic neurons, including the facilitatory and inhibitory controls that originate from so-called "on" and "off" cells of the rostroventral medulla (RVM). Unclear, however, is the extent to which these latter circuits interact with or are influenced by the serotonergic cell groups. To address this question we selectively targeted expression of a transneuronal tracer, wheat germ agglutinin (WGA), in the 5HT neurons so as to study the interplay between the 5HT and non-5HT systems. In addition to confirming the direct medullary 5HT projection to the spinal cord we also observed large numbers of non-5HT neurons, in the medullary nucleus reticularis gigantocellularis and magnocellularis, that were WGA-immunoreactive, i.e., were transneuronally labeled from 5HT neurons. FluoroGold injections into the spinal cord established that these reticular neurons are not only postsynaptic to the 5HT neurons of the medulla, but that most are also at the origin of descending, bulbospinal pathways. By contrast, we found no evidence that neurons of the midbrain periaqueductal gray that project to the RVM are postsynaptic to midbrain or medullary 5HT neurons. Finally, we found very few examples of WGA-immunoreactive noradrenergic neurons, which suggests that there is considerable independence of the monoaminergic bulbospinal pathways. Our results indicate that 5HT neurons influence "pain" processing at the spinal cord level both directly and indirectly via feedforward connections with multiple non-5HT descending control pathways.