Department of Biology, Boston University, Boston, Massachusetts 02215, USA.
J Neurophysiol. 2010 Feb;103(2):648-58. doi: 10.1152/jn.00827.2009. Epub 2009 Dec 2.
Serotonin initiates various rhythmic behaviors in vertebrates. Previously we have shown that serotonergic neurons innervate the central vocal pathway in the African clawed frog (Xenopus laevis). We also discovered that exogenous serotonin applied to isolated brains in vitro activates fictive vocalizations by activating 5-HT(2C)-like receptors. In this study, we examined the location of 5-HT(2C)-like receptors and determined whether endogenously released serotonin also initiates vocalizations by activating 5-HT(2C)-like receptors in male Xenopus brains. To this end, we first identified the specific location of 5-HT(2C)-like receptors using immunohistochemistry. We next examined which of the populations of neurons that express 5-HT(2C)-like receptors are functionally relevant for initiating fictive vocalizations by applying a 5-HT(2C) receptor agonist to brains transected at various levels. Of four populations of immunopositive neurons, we showed that 5-HT(2C)-like receptors located in two areas of the brain stem vocal circuit, the raphe nucleus and motor nucleus IX-X, initiate fictive vocalizations. We next showed that endogenous serotonin can also activate fictive vocalizations by increasing the extracellular concentration of endogenous serotonin using a selective serotonin reuptake inhibitor (SSRI). The SSRI-induced vocal initiation is also mediated by activation of 5-HT(2C)-like receptors because blockade of these receptors prevents fictive vocalization. The results suggest that in vivo release of serotonin initiates male vocalizations by activating 5-HT(2C)-like receptors in the brain stem vocal nuclei.
血清素在脊椎动物中引发各种节律性行为。我们之前已经表明，血清素能神经元支配非洲爪蟾（Xenopus laevis）的中枢发声途径。我们还发现，外源性血清素通过激活 5-HT2C 样受体在离体脑内应用可激活拟声发声。在这项研究中，我们检查了 5-HT2C 样受体的位置，并确定内源性释放的血清素是否也通过激活雄性非洲爪蟾脑中的 5-HT2C 样受体来引发发声。为此，我们首先使用免疫组织化学鉴定 5-HT2C 样受体的特定位置。接下来，我们通过在不同水平横切脑，应用 5-HT2C 受体激动剂来检查表达 5-HT2C 样受体的神经元群体中，哪些神经元群体对启动拟声发声具有功能相关性。在四种免疫阳性神经元群体中，我们表明，位于脑干发声回路的两个区域（中缝核和运动核 IX-X）中的 5-HT2C 样受体可引发拟声发声。接下来，我们还表明，通过使用选择性 5-羟色胺再摄取抑制剂（SSRI）增加内源性 5-羟色胺的细胞外浓度，内源性 5-羟色胺也可以激活拟声发声。SSRI 诱导的发声起始也通过激活 5-HT2C 样受体介导，因为这些受体的阻断可防止拟声发声。这些结果表明，在体内释放的血清素通过激活脑干发声核中的 5-HT2C 样受体来引发雄性发声。
