Inputs to Serotonergic Neurons Revealed by Conditional Viral Transneuronal Tracing
Inputs to Serotonergic Neurons Revealed by Conditional Viral Transneuronal Tracing
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DOI：
10.1002/cne.22003
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发表时间：
2009-05-10
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 M.;Enquist, Lynn W.;Basbaum, Allan I.
脑干5-羟色胺(5-羟色胺)能神经元的下行投射对脊髓痛传递神经元的易化和抑制控制均有贡献。然而，影响这些5-羟色胺神经元输出的脑干网络尚不清楚。为了解决这个问题，我们在转基因小鼠(ePet-Cre小鼠)中使用了一种新的神经解剖学示踪方法，在该转基因小鼠中，Cre重组酶选择性地在5HT神经元中表达。具体地说，我们注射了条件伪狂犬病病毒重组(BA2001)，它只能在表达Cre的神经元中复制。由于BA2001仅以逆行方式运输，我们能够揭示出位于表达CRE的5HT神经元上游的神经元和电路的一个子集。我们发现，不同的脑干区域不同地以中缝背核(DR)和中缝大核(RVM)的5HT神经元为靶标。其中包括几个儿茶酚胺能和胆碱能细胞群、中脑导水管周围灰质、几个脑干网状核和孤束核。我们的结论是，脑5HT网络整合了来自身体不同区域的躯体和内脏输入。我们还发现了一个来自脊髓深层V-VIII层的投射神经元的回路，它针对的是NRM的5HT神经元，而不是DR的5HT神经元。这条脊髓网状通路构成了一个解剖底物，伤害性刺激可以通过它激活NRM的5HT神经元，进而触发下行的5-羟色胺能抗伤害性反应。J.Comp.神经。2009年，514：145-160。(C)2009年Wiley-Liss，Inc.
Descending projections arising from brainstem serotonergic (5HT) neurons contribute to both facilitatory and inhibitory controls of spinal cord "pain" transmission neurons. Unclear, however, are the brainstem networks that influence the output of these 5HT neurons. To address this question, here we used a novel neuroanatomical tracing method in a transgenic line of mice in which Cre recombinase Is selectively expressed in 5HT neurons (ePet-Cre mice). Specifically, we injected the conditional pseudorabies virus recombinant (BA2001) that can replicate only in Cre-expressing neurons. Because BA2001 transports exclusively In a retrograde manner, we were able to reveal a subset of the neurons and circuits that are located upstream of the Cre-expressing 5HT neurons. We show that diverse brainstem regions differentially target the 5HT neurons of the dorsal raphe (DR) and the nucleus raphe magnus of the rostroventral medulla (RVM). Among these are several catecholaminergic and cholinergic cell groups, the periaqueductal gray, several brainstem reticular nuclei, and the nucleus of the solitary tract. We conclude that a brainsterm 5HT network integrates somatic and visceral inputs arising from various areas of the body. We also identified a circuit that arises from projection neurons of deep spinal cord laminae V-VIII and targets the 5HT neurons of the NRM, but not of,the DR. This spinoreticular pathway constitutes an anatomical substrate through which a noxious stimulus can activate 5HT neurons of the NRM and in turn could trigger descending serotonergic antinociceptive controls. J. Comp. Neurol. 514:145-160, 2009. (C) 2009 Wiley-Liss, Inc.