High glucose increases action potential firing of catecholamine neurons in the nucleus of the solitary tract by increasing spontaneous glutamate inputs
High glucose increases action potential firing of catecholamine neurons in the nucleus of the solitary tract by increasing spontaneous glutamate inputs
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DOI：
10.1152/ajpregu.00413.2016
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发表时间：
2017-09-01
影响因子：
2.8
通讯作者：
Appleyard, Suzanne M.
中科院分区：
文献类型：
--
作者：
Roberts, Brandon L.;Zhu, Mingyan;Appleyard, Suzanne M.
葡萄糖是细胞生存和功能的重要底物。葡萄糖水平的变化会影响神经元活动，而葡萄糖剥夺会增加进食。几个大脑区域已被证明对葡萄糖活化有反应，包括脑干的孤立束核（NTS）。NTS是大脑中接收来自胃肠道的内脏传入信息的主要部位。NTS中的儿茶酚胺能（CA）亚群调节许多稳态功能，包括心血管反射、呼吸、食物摄入、觉醒和应激。然而，尚不清楚它们是否对葡萄糖的变化有反应。在这里，我们确定了NTS-CA神经元是否对葡萄糖浓度的变化作出反应及其机制。我们发现，将葡萄糖浓度从5毫米降低到2毫米，再降低到1毫米，可以显著降低细胞附着制备中的动作电位放电，而将葡萄糖浓度增加到5毫米，则可以增加动作电位放电速率。这种作用依赖于传入末端的谷氨酸释放，需要突触前5-HT(3)Rs。葡萄糖浓度的降低也降低了基础和5-HT3R激动剂诱导的NTS-CA神经元自发性谷氨酸输入频率的增加。低糖还减弱了5- ht诱导的结节神经节神经元的内向电流，结节神经节是迷走神经传入的细胞体。低糖对结节神经节细胞和NTS切片的影响由葡萄糖激酶抑制剂氨基葡萄糖模拟。这项研究表明，NTS-CA神经元通过突触前机制进行糖感，该机制依赖于迷走神经谷氨酸释放、5-HT3R活性和葡萄糖激酶。
Glucose is a crucial substrate essential for cell survival and function. Changes in glucose levels impact neuronal activity and glucose deprivation increases feeding. Several brain regions have been shown to respond to glucoprivation, including the nucleus of the solitary tract (NTS) in the brain stem. The NTS is the primary site in the brain that receives visceral afferent information from the gastrointestinal tract. The catecholaminergic (CA) subpopulation within the NTS modulates many homeostatic functions including cardiovascular reflexes, respiration, food intake, arousal, and stress. However, it is not known if they respond to changes in glucose. Here we determined whether NTS-CA neurons respond to changes in glucose concentration and the mechanism involved. We found that decreasing glucose concentrations from 5 mM to 2 mM to 1 mM, significantly decreased action potential firing in a cell-attached preparation, whereas increasing it back to 5 mM increased the firing rate. This effect was dependent on glutamate release from afferent terminals and required presynaptic 5-HT(3)Rs. Decreasing the glucose concentration also decreased both basal and 5-HT3R agonist-induced increase in the frequency of spontaneous glutamate inputs onto NTS-CA neurons. Low glucose also blunted 5-HT-induced inward currents in nodose ganglia neurons, which are the cell bodies of vagal afferents. The effect of low glucose in both nodose ganglia cells and in NTS slices was mimicked by the glucokinase inhibitor glucosamine. This study suggests that NTS-CA neurons are glucosensing through a presynaptic mechanism that is dependent on vagal glutamate release, 5-HT3R activity, and glucokinase.