Ghrelin modulates lateral amygdala neuronal firing and blocks acquisition for conditioned taste aversion.

Ghrelin modulates lateral amygdala neuronal firing and blocks acquisition for conditioned taste aversion.
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生长素释放肽调节外侧杏仁核神经元放电并阻止条件性味觉厌恶的获取

DOI:
10.1371/journal.pone.0065422
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发表时间:
2013
期刊:
影响因子:
3.7
通讯作者:
Zhou Y
Zhou Y
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Song L;Zhu Q;Liu T;Yu M;Xiao K;Kong Q;Zhao R;Li GD;Zhou Y

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Ghrelin是一种促食欲的脑肠激素,在人和啮齿动物中促进摄食和调节能量代谢。越来越多的研究报道,Ghrelin及其识别的受体生长激素促分泌素受体1a(GHS-R1a)对中枢神经系统中特定的神经元群产生广泛而复杂的功能和生物学效应。在本研究中,我们试图从生理和行为水平探讨急性Ghrelin暴露对杏仁外侧核(LA)神经元的影响。在活体细胞外单位记录显示,几个纳米分子(NM)浓度的Ghrelin刺激LA神经元的自发放电,这种作用呈剂量依赖关系,并可被GHS-R1a拮抗剂D-Lys3-GHRP-6共同应用所阻断。我们还发现D-Lys3-GHRP-6以剂量依赖的方式抑制LA神经元的自发放电,这表明紧张性GHS-R1a活动有助于协调LA神经元的基础活动。在行为学上,我们发现训练前向LA微量注射Ghrelin(12 Ng)会干扰条件化味觉厌恶(CTA)的获得,这是在条件化后24小时测试的。用纯化的抗GHS-R1a的Ig G或GHS-R1a拮抗剂预先处理可阻断Ghrelin对CTA记忆获得的影响。Ghrelin(12 Ng)对大鼠的CTA记忆巩固和获得性CTA记忆表达没有影响,也不影响受试大鼠的总液体消耗量。综上所述,我们的数据表明,局部注入La的Ghrelin阻断了CTA的获得,其对神经元放电的调制作用可能参与了这一过程。
Ghrelin is an orexigenic brain-gut hormone promoting feeding and regulating energy metabolism in human and rodents. An increasing number of studies have reported that ghrelin and its identified receptor, the growth hormone secretagogue receptor 1a (GHS-R1a), produces remarkably wide and complex functions and biological effects on specific populations of neurons in central nervous system. In this study, we sought to explore the in vivo effects of acute ghrelin exposure on lateral amygdala (LA) neurons at the physiological and behavioral levels. In vivo extracellular single-unit recordings showed that ghrelin with the concentration of several nanomolars (nM) stimulated spontaneous firing of the LA neurons, an effect that was dose-dependent and could be blocked by co-application of a GHS-R1a antagonist D-Lys3-GHRP-6. We also found that D-Lys3-GHRP-6 inhibited spontaneous firing of the LA neurons in a dose-dependent manner, revealing that tonic GHS-R1a activity contributes to orchestrate the basal activity of the LA neurons. Behaviorally, we found that microinfusion of ghrelin (12 ng) into LA before training interfered with the acquisition of conditioned taste aversion (CTA) as tested at 24 h after conditioning. Pre-treatment with either purified IgG against GHS-R1a or GHS-R1a antagonist blocked ghrelin’s effect on CTA memory acquisition. Ghrelin (12 ng) had no effect on CTA memory consolidation or the expression of acquired CTA memory; neither did it affect the total liquid consumption of tested rats. Altogether, our data indicated that ghrelin locally infused into LA blocks acquisition of CTA and its modulation effects on neuronal firing may be involved in this process.
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