Serotonergic modulation of the activity of GLP-1 producing neurons in the nucleus of the solitary tract in mouse.
Serotonergic modulation of the activity of GLP-1 producing neurons in the nucleus of the solitary tract in mouse.
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DOI：
10.1016/j.molmet.2017.06.002
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发表时间：
2017-08
影响因子：
8.1
通讯作者：
Trapp S
中科院分区：
文献类型：
--
作者：
Holt MK;Llewellyn-Smith IJ;Reimann F;Gribble FM;Trapp S
胰升糖素样肽-1(GLP-1)和5-羟色胺是大脑内食物摄取的有效调节剂。GLP-1由孤束核(NTS)内的胰高血糖素原(PPG)神经元表达。我们先前已经证明，PPG神经元支配腹侧脑干中的5-羟色胺神经元。在这里，我们研究PPG神经元是否接受5-羟色胺能输入并对5-羟色胺作出反应。用免疫组织化学方法显示PPG神经元的5-羟色胺能神经支配。我们利用PPG神经元中表达钙指示剂GCaMP3的转基因小鼠脑干切片的体外钙成像和细胞附着式膜片钳记录，研究了PPG神经元对5-羟色胺的反应性。在许多PPG神经元上可见5-羟色胺免疫反应阳性轴突的紧密联系。应用20μM 5-羟色胺后，NTS PPG树突的钙反应较强，而胞体变化不大。树突状钙峰电流呈浓度依赖性(2、20和200μM)，不受谷氨酸能传递阻断的影响，提示PPG神经元上存在5-羟色胺受体。5-HT3受体的激活或阻断均不影响[Ca~(2+)]i。相反，抑制5-HT2受体可减弱细胞内钙的升高，而5-HT2C受体的激活可产生钙尖峰。膜片钳记录显示，44%的细胞在5-羟色胺作用下放电频率降低，这一作用可被5-HT1a受体拮抗剂阻断。PPG神经元对5-羟色胺的直接反应是依赖5-HT2C受体的树突状细胞内[Ca~(2+)]i的增加，而对5-羟色胺的电反应则表现为躯体5-HT1a受体的额外抑制作用。5-羟色胺和PPG神经元之间的相互神经支配提示，这些脑干神经元的协调活动可能在食物摄入量的调节中发挥作用。脑干PPG神经元接受含有5-羟色胺的轴突的紧密联系。5-羟色胺通过5-HT2受体直接激活NTS PPG树突。5-羟色胺通过5-HT1a受体抑制体细胞的一个亚群。激活5-HT3受体不影响PPG细胞[Ca~(2+)]i。5-HT2C受体激活可诱导PPG神经元空间受限的Ca~(2+)峰。
Glucagon-like peptide-1 (GLP-1) and 5-HT are potent regulators of food intake within the brain. GLP-1 is expressed by preproglucagon (PPG) neurons in the nucleus tractus solitarius (NTS). We have previously shown that PPG neurons innervate 5-HT neurons in the ventral brainstem. Here, we investigate whether PPG neurons receive serotonergic input and respond to 5-HT. We employed immunohistochemistry to reveal serotonergic innervation of PPG neurons. We investigated the responsiveness of PPG neurons to 5-HT using in vitro Ca2+ imaging in brainstem slices from transgenic mice expressing the Ca2+ indicator, GCaMP3, in PPG neurons, and cell-attached patch-clamp recordings. Close appositions from 5-HT-immunoreactive axons occurred on many PPG neurons. Application of 20 μM 5-HT produced robust Ca2+ responses in NTS PPG dendrites but little change in somata. Dendritic Ca2+ spikes were concentration-dependent (2, 20, and 200 μM) and unaffected by blockade of glutamatergic transmission, suggesting 5-HT receptors on PPG neurons. Neither activation nor blockade of 5-HT3 receptors affected [Ca2+]i. In contrast, inhibition of 5-HT2 receptors attenuated increases in intracellular Ca2+ and 5-HT2C receptor activation produced Ca2+ spikes. Patch-clamp recordings revealed that 44% of cells decreased their firing rate under 5-HT, an effect blocked by 5-HT1A receptor antagonism. PPG neurons respond directly to 5-HT with a 5-HT2C receptor-dependent increase in dendritic [Ca2+]i. Electrical responses to 5-HT revealed additional inhibitory effects due to somatic 5-HT1A receptors. Reciprocal innervation between 5-HT and PPG neurons suggests that the coordinated activity of these brainstem neurons may play a role in the regulation of food intake. Brainstem PPG neurons receive close appositions from 5-HT-containing axons. 5-HT activates NTS PPG dendrites directly via 5-HT2 receptors. 5-HT inhibits a subset of somata via 5-HT1A receptors. Activation of 5-HT3 receptors does not affect PPG cell [Ca2+]i. 5-HT2C receptor activation induces spatially confined Ca2+ spikes in PPG neurons.
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影响因子：
3.3
作者：
Llewellyn-Smith, I. J.;Reimann, F.;Gribble, F. M.;Trapp, S.
通讯作者：
Trapp, S.
影响因子：
3.3
作者：
Llewellyn-Smith, I. J.;Gnanamanickam, G. J. E.;Reimann, F.;Gribble, F. M.;Trapp, S.
通讯作者：
Trapp, S.
影响因子：
3.3
作者：
Larsen, PJ;TangChristensen, M;Orskov, C
通讯作者：
Orskov, C
影响因子：
10.8
作者：
Griffioen, Kathleen J.;Wan, Ruiqian;Mattson, Mark P.
通讯作者：
Mattson, Mark P.
影响因子：
--
作者：
Holt MK;Trapp S
通讯作者：
Trapp S