Proopiomelanocortin expression in both GABA and glutamate neurons.
Proopiomelanocortin expression in both GABA and glutamate neurons.
复制标题
DOI：
10.1523/jneurosci.3770-09.2009
复制
发表时间：
2009-10-28
期刊：
影响因子：
--
通讯作者：
Low MJ
中科院分区：
文献类型：
--
作者：
Hentges ST;Otero-Corchon V;Pennock RL;King CM;Low MJ
阿黑皮素原（POMC）神经元由于其在调节能量平衡和体重中的重要作用而被广泛研究。POMC神经元的许多作用可归因于其从轴突终末的分泌颗粒中释放同源神经肽。然而，这些神经元也通过突触释放非肽类神经递质。这项研究的目的是解决是否有单独的POMC神经元群体释放GABA或谷氨酸的争议。将表达由Pomc神经元调节元件驱动的红色荧光蛋白的转基因小鼠（POMC-DsRed）与在GABA能神经元中表达绿色荧光蛋白的小鼠（GAD 67-gfp）杂交。双转基因小鼠的弓状核中约40%的POMC神经元表达GAD 67-gfp转基因。在体外神经递质释放检测使用培养的GAD 67-GFP阳性和阴性POMC神经元，已形成复发性突触（autapses）的全细胞电生理记录。GAD 67-gfp阳性神经元的自贴物是均匀的GABA能的。相反，GAD 67-gfp阴性POMC神经元的autapses只表现出谷氨酸介导的突触后电流。总之，这些结果表明，有两个亚群的POMC神经元在弓状核分化的氨基酸神经递质表型。全细胞电压钳记录POMC神经元在活脑切片中表明，GABA能和多巴胺能POMC神经元在相似的突触前和突触后的调节下，虽然GABA能POMC神经元更小，具有更高的输入电阻。GABA能和谷氨酸能POMC神经元可以介导POMC神经元功能的不同方面，包括能量稳态的调节。
Proopiomelanocortin (POMC) neurons have been intensively studied because of their essential role in regulating energy balance and body weight. Many effects of POMC neurons can be attributed to their release of cognate neuropeptides from secretory granules in axon terminals. However, these neurons also synaptically release non-peptide neurotransmitters. The aim of this study was to settle the controversy whether there are separate populations of POMC neurons that release GABA or glutamate. Transgenic mice expressing a red fluorescent protein driven by Pomc neuronal regulatory elements (POMC-DsRed) were crossed to mice that expressed green fluorescent protein in GABAergic neurons (GAD67-gfp). Approximately 40% of POMC neurons in the arcuate nucleus of the double transgenic mice expressed the GAD67-gfp transgene. In vitro neurotransmitter release was detected using whole-cell electrophysiologic recordings in cultured GAD67-gfp-positive and -negative POMC neurons that had formed recurrent synapses (autapses). Autapses from GAD67-gfp-positive neurons were uniformly GABAergic. In contrast, autapses from the GAD67-gfp-negative POMC neurons exclusively exhibited postsynaptic currents mediated by glutamate. Together, these results indicate that there are two subpopulations of POMC neurons in the arcuate nucleus differentiated by their amino acid neurotransmitter phenotype. Whole-cell voltage-clamp recordings from POMC neurons in live brain slices indicated that GABAergic and glutamatergic POMC neurons are under similar pre- and post-synaptic regulation although the GABAergic POMC neurons are smaller and have higher input resistance. GABAergic and glutamatergic POMC neurons may mediate distinct aspects of POMC neuron function, including the regulation of energy homeostasis.