Abstract:
Rapid non-genomic effects of corticosteroid hormones, affecting glutamatergic and GABAergic transmission, have been described for many limbic structures in the rodent brain. These rapid effects appear to be region specific. It is not always clear which (or even whether) corticosteroid receptor -the glucocorticoid receptor (GR) or mineralocorticoid receptor (MR)- initiate these rapid effects. In the hippocampus and amygdala membrane-associated MR, but also membrane-associated GR (in amygdala), are involved. Other studies indicate that the rapid modulation may be induced by transactivation of kinases, or other receptors, like the G-protein coupled estrogen receptor (GPER) which was recently found to bind the mineralocorticoid aldosterone. In the current study we explored, in young adult male C57Bl6 mice, possible rapid effects of corticosterone on layer 2/3 infralimbic-prefrontal cortex (IL-PFC) neurons. We show that corticosterone, via non-genomic MR activation, reduces the mEPSC -but does not affect mIPSC- frequency; we observed no effect on mEPSC or mIPSC amplitude. As a result, overall spontaneous activity in the IL-PFC is suppressed. A potential role of GPER cannot be excluded, since G-15, an antagonist of GPER, also prevented the rapid effects of corticosterone.
摘要:
皮质类固醇激素的快速非基因组效应,影响谷氨酸能和GABA能传递,已经被描述为啮齿动物大脑中的许多边缘结构。这些快速影响似乎是特定地区的。尚不清楚哪种(甚至是否)皮质类固醇受体-糖皮质激素受体(GR)或盐皮质激素受体(MR)-引发这些快速作用。在海马体和杏仁核膜相关的MR中,还有膜相关的GR(在杏仁核中),参与其中。其他研究表明,快速调节可能是由激酶的反式激活诱导的,或其他受体,例如最近发现的G蛋白偶联雌激素受体(GPER)与盐皮质激素醛固酮结合。在我们探索的当前研究中,在年轻成年雄性C57Bl6小鼠中,皮质酮对2/3层前额叶皮层(IL-PFC)神经元的可能快速作用。我们显示皮质酮,通过非基因组MR激活,降低mEPSC-但不影响mIPSC-频率;我们观察到对mEPSC或mIPSC振幅没有影响。因此,IL-PFC的总体自发活性被抑制。不能排除GPER的潜在作用,自GPER的拮抗剂G-15以来,也阻止了皮质酮的快速作用。