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Somatostatin varicosities contain the vesicular GABA transporter and contact orexin neurons in the hypothalamus

机译:生长抑素静脉曲张包含下丘脑中的囊泡GABA转运蛋白和接触性食欲素神经元

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Somatostatin (SST) is a neuropeptide with known inhibitory actions in the hypothalamus, where it inhibits release of growth hormone-releasing hormone (GHRH), while also influencing the sleep-wake cycle. Here we investigated in the rat whether SST neurons might additionally release GABA (gamma-aminobutyric acid) or glutamate in different regions and whether they might contact orexin neurons that play an important role in the maintenance of wakefulness. In dual-immunostained sections viewed by epifluorescence microscopy, we examined if SST varicosities were immunopositive for the vesicular transporter for GABA (VGAT) or glutamate (VGLUT2) in the posterolateral hypothalamus and neighboring arcuate nucleus and median eminence. Of the SST varicosities in the posterolateral hypothalamus, 18% were immunopositive for VGAT, whereas ≤1% were immunopositive for VGLUT2. In the arcuate and median eminence, 26 and 64% were VGAT+ and <3% VGLUT2+, respectively. In triple-immunostained sections viewed by epifluorescence and confocal microscopy, SST varicosities were seen in contact with orexin somata, and of these varicosities, a significant proportion (23%) contained VGAT along with synaptophysin, the presynaptic marker for small synaptic vesicles, and a similar proportion (25%) abutted puncta that were immunostained for gephyrin, the postsynaptic marker for GABAergic synapses. Our results indicate that a significant proportion of SST varicosities in the hypothalamus have the capacity to release GABA, to form inhibitory synapses upon orexin neurons, and accordingly through their peptide and/or amino acid, to inhibit orexin neurons, as well as GHRH neurons. Thus while regulating GHRH release, SST neurons could serve to attenuate arousal and permit progression through the sleep cycle.
机译:生长抑素(SST)是在下丘脑中具有已知抑制作用的神经肽,在该肽中它抑制生长激素释放激素(GHRH)的释放,同时还影响睡眠-觉醒周期。在这里,我们研究了大鼠SST神经元是否会在不同区域另外释放GABA(γ-氨基丁酸)或谷氨酸,以及它们是否可能与在维持觉醒中起重要作用的orexin神经元接触。在通过落射荧光显微镜观察的双重免疫染色切片中,我们检查了SST静脉曲张是否对后外侧下丘脑及邻近弓状核和中位隆起的GABA(VGAT)或谷氨酸(VGLUT2)的囊泡转运蛋白免疫阳性。在后外侧下丘脑的SST静脉曲张中,18%的VGAT免疫阳性,而≤1%的VGLUT2免疫阳性。在弧形和中间突出度中,分别为VGAT +和VGLUT2 +分别为26%和64%。在通过落射荧光和共聚焦显微镜观察的三重免疫染色切片中,观察到SST静脉曲张与食欲素躯体接触,在这些静脉曲张中,显着比例(23%)包含VGAT以及突触素,突触前小突触囊泡标记物和比例接近(25%)的点状点已被gephyrin免疫染色,gephyrin是GABA能突触的突触后标记。我们的结果表明,下丘脑中很大比例的SST静脉曲张具有释放GABA,在orexin神经元上形成抑制性突触的能力,并因此通过其肽和/或氨基酸来抑制orexin神经元以及GHRH神经元。因此,在调节GHRH释放的同时,SST神经元可用于减弱唤醒并允许其进入整个睡眠周期。

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