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首页> 外文期刊>The European Journal of Neuroscience >Vesicular glutamate transporter 2 is required for the respiratory and parasympathetic activation produced by optogenetic stimulation of catecholaminergic neurons in the rostral ventrolateral medulla of mice in vivo
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Vesicular glutamate transporter 2 is required for the respiratory and parasympathetic activation produced by optogenetic stimulation of catecholaminergic neurons in the rostral ventrolateral medulla of mice in vivo

机译:通过在体内小鼠小鼠的小鼠呼吸术髓鞘髓质中,通过致敏刺激产生的呼吸和副交感神经激活所需的呼吸和途径转运蛋白。

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摘要

Catecholaminergic neurons of the rostral ventrolateral medulla (RVLM-CA neurons; C1 neurons) contribute to the sympathetic, parasympathetic and neuroendocrine responses elicited by physical stressors such as hypotension, hypoxia, hypoglycemia, and infection. Most RVLM-CA neurons express vesicular glutamate transporter (VGLUT)2, and may use glutamate as a ionotropic transmitter, but the importance of this mode of transmission in vivo is uncertain. To address this question, we genetically deleted VGLUT2 from dopamine-β-hydroxylase-expressing neurons in mice [DβHCre/0;VGLUT2flox/flox mice (cKO mice)]. We compared the in vivo effects of selectively stimulating RVLM-CA neurons in cKO vs. control mice (DβHCre/0), using channelrhodopsin-2 (ChR2-mCherry) optogenetics. ChR2-mCherry was expressed by similar numbers of rostral ventrolateral medulla (RVLM) neurons in each strain (~400 neurons), with identical selectivity for catecholaminergic neurons (90-99% colocalisation with tyrosine hydroxylase). RVLM-CA neurons had similar morphology and axonal projections in DβHCre/0 and cKO mice. Under urethane anesthesia, photostimulation produced a similar pattern of activation of presumptive ChR2-positive RVLM-CA neurons in DβHCre/0 and cKO mice. Photostimulation in conscious mice produced frequency-dependent respiratory activation in DβHCre/0 mice but no effect in cKO mice. Similarly, photostimulation under urethane anesthesia strongly activated efferent vagal nerve activity in DβHCre/0 mice only. Vagal responses were unaffected by α1-adrenoreceptor blockade. In conclusion, two responses evoked by RVLM-CA neuron stimulation in vivo require the expression of VGLUT2 by these neurons, suggesting that the acute autonomic responses driven by RVLM-CA neurons are mediated by glutamate.
机译:讲鼻腔外髓质髓质的儿茶酚胺能神经元(RVLM-CA神经元; C1神经元)有助于由物理压力源引起的同情,副交感神经和神经内分泌反应,例如低血压,缺氧,低血糖和感染。大多数RVLM-CA神经元表达凹凸谷氨酸转运蛋白(VGLUT)2,并可使用谷氨酸作为离子脱发器,但这种传播模式的重要性是不确定的。为了解决这个问题,我们在小鼠中转基因从小鼠的多巴胺-β-羟化酶的神经元进行遗传删除Vglut2 [dβhcre/ 0; Vglut2flox / flox小鼠(CKO小鼠)]。我们使用沟道流水解蛋白-2(CHR2-MCHERRY)光学探测,比较了在CKO与对照小鼠(DβHCRE/ 0)中选择性刺激RVLM-CA神经元的体内效果。 CHR2-MCHERRY在每个菌株(〜400神经元)中的相似数量的r旋转介口髓质髓质(RVLM)神经元表达,具有相同的儿茶酚胺能神经元的选择性(90-99%与酪氨酸羟化酶的离子化)。 RVLM-CA神经元在DβHCRE/ 0和CKO小鼠中具有相似的形态和轴突突起。在氨基甲酸酯麻醉下,光致刺激在DβHCRE/ 0和CKO小鼠中产生了类似的推定CHR2阳性RVLM-CA神经元的活化模式。在有意识的小鼠中的光刺激产生DβHCRE/ 0小鼠的频率依赖性呼吸系统活化,但在CKO小鼠中没有作用。类似地,在氨基甲酸酯麻醉下的光刺激仅在DβHCRE/ 0小鼠中强烈激活了动力神经活性。缩陷的反应不受α1-肾上腺素封闭的影响。总之,VIVO中RVLM-CA神经元刺激引起的两种反应需要这些神经元的VGLUT2的表达,这表明RVLM-CA神经元驱动的急性自主反应由谷氨酸介导。

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