Nucleus-specific modulation of phasic and tonic inhibition by endogenous neurosteroidogenesis in the murine thalamus.,SYNAPSE

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Nucleus-specific modulation of phasic and tonic inhibition by endogenous neurosteroidogenesis in the murine thalamus.
SYNAPSE ( IF 1.6 ) Pub Date : 2019-12-08 , DOI: 10.1002/syn.22144
Catherine A Christian _{1,

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Affiliation

Neurosteroids are potent allosteric modulators of GABAA receptors (GABAA Rs). Although the effects of exogenous neurosteroids on GABAA R function are well documented, less is known about effects of neurosteroids produced by local endogenous biosynthesis. The neurosteroidogenic enzymes 5α-reductase and 3α-hydroxysteroid dehydrogenase are expressed in two nuclei of somatosensory thalamus, the thalamic reticular nucleus (nRT) and ventrobasal nucleus (VB). Here, the effects of acute blockade of neurosteroidogenesis by the 5α-reductase inhibitor finasteride on phasic and tonic GABAA R-mediated currents were examined in nRT and VB of mice. In nRT, finasteride altered the decay and amplitude, but not the frequency, of phasic currents, with no effect on tonic inhibition. In VB neurons, by contrast, finasteride reduced both the size and frequency of phasic currents, and also reduced the degree of tonic inhibition. These studies thus provide novel evidence for endogenous modulation of GABAA R function by 5α-reduced neurosteroids in the mature thalamus.

中文翻译：

鼠丘脑内源性神经类固醇生成对相位和强直抑制的细胞核特异性调节。

神经类固醇是 GABAA 受体 (GABAA Rs) 的有效变构调节剂。尽管外源性神经类固醇对 GABAA R 功能的影响已得到充分证明，但对局部内源性生物合成产生的神经类固醇的影响知之甚少。神经类固醇生成酶 5α-还原酶和 3α-羟基类固醇脱氢酶在体感丘脑的两个核、丘脑网状核 (nRT) 和腹基底核 (VB) 中表达。在这里，在小鼠的 nRT 和 VB 中检查了 5α-还原酶抑制剂非那雄胺对神经类固醇生成的急性阻断对时相和强直 GABAA R 介导的电流的影响。在 nRT 中，非那雄胺改变了相位电流的衰减和幅度，但不改变频率，对强直抑制没有影响。相比之下，在 VB 神经元中，非那雄胺降低了相位电流的大小和频率，也降低了强直抑制的程度。因此，这些研究为成熟丘脑中 5α 减少的神经类固醇对 GABAA R 功能的内源性调节提供了新的证据。

更新日期：2020-03-27

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