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中央松弛素-3 受体 (RXFP3) 的激活会损害社会识别能力,并调节特定 GABA 能杏仁核神经元中的 ERK 磷酸化。

Central relaxin-3 receptor (RXFP3) activation impairs social recognition and modulates ERK-phosphorylation in specific GABAergic amygdala neurons.

机构信息

Departamento de Medicina, Facultad de Ciencias de la Salud, Universitat Jaume I, Av de Vicent Sos Baynat, s/n, 12071, Castellón de la Plana, Castellón, Spain.

Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK.

出版信息

Brain Struct Funct. 2019 Jan;224(1):453-469. doi: 10.1007/s00429-018-1763-5. Epub 2018 Oct 28.

DOI:10.1007/s00429-018-1763-5
PMID:30368554
Abstract

In mammals, the extended amygdala is a neural hub for social and emotional information processing. In the rat, the extended amygdala receives inhibitory GABAergic projections from the nucleus incertus (NI) in the pontine tegmentum. NI neurons produce the neuropeptide relaxin-3, which acts via the G-protein-coupled receptor, RXFP3. A putative role for RXFP3 signalling in regulating social interaction was investigated by assessing the effect of intracerebroventricular infusion of the RXFP3 agonist, RXFP3-A2, on performance in the 3-chamber social interaction paradigm. Central RXFP3-A2, but not vehicle, infusion, disrupted the capacity to discriminate between a familiar and novel conspecific subject, but did not alter differentiation between a conspecific and an inanimate object. Subsequent studies revealed that agonist-infused rats displayed increased phosphoERK(pERK)-immunoreactivity in specific amygdaloid nuclei at 20 min post-infusion, with levels similar to control again after 90 min. In parallel, we used immunoblotting to profile ERK phosphorylation dynamics in whole amygdala after RXFP3-A2 treatment; and multiplex histochemical labelling techniques to reveal that after RXFP3-A2 infusion and social interaction, pERK-immunopositive neurons in amygdala expressed vesicular GABA-transporter mRNA and displayed differential profiles of RXFP3 and oxytocin receptor mRNA. Overall, these findings demonstrate that central relaxin-3/RXFP3 signalling can modulate social recognition in rats via effects within the amygdala and likely interactions with GABA and oxytocin signalling.

摘要

在哺乳动物中,扩展的杏仁核是社交和情感信息处理的神经中枢。在大鼠中,扩展的杏仁核接收来自桥脑被盖的未定核(NI)的抑制性 GABA 能投射。NI 神经元产生神经肽松弛素 3,通过 G 蛋白偶联受体 RXFP3 发挥作用。通过评估脑室内输注 RXFP3 激动剂 RXFP3-A2 对 3 室社交互动范式中表现的影响,研究了 RXFP3 信号在调节社交互动中的作用。中枢 RXFP3-A2,但不是载体,输注,破坏了区分熟悉和陌生同种异体主体的能力,但不改变同种异体和无生命物体之间的分化。随后的研究表明,激动剂输注的大鼠在输注后 20 分钟在特定的杏仁核核中显示出增加的磷酸化 ERK(pERK)-免疫反应性,在 90 分钟后再次与对照相似。平行地,我们使用免疫印迹来分析 RXFP3-A2 处理后整个杏仁核中的 ERK 磷酸化动力学;和多指标组织化学标记技术显示,在 RXFP3-A2 输注和社交互动后,杏仁核中 pERK 免疫阳性神经元表达囊泡 GABA 转运体 mRNA,并显示出 RXFP3 和催产素受体 mRNA 的不同表达谱。总的来说,这些发现表明,中枢松弛素 3/RXFP3 信号可以通过杏仁核内的效应以及与 GABA 和催产素信号的可能相互作用来调节大鼠的社交识别。

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