Department of Nano-Bioengineering, Incheon National University, Incheon 406-772, Korea.
Division of Life Sciences, College of Life Sciences and Bioengineering, Incheon National University, Incheon 406-772, Korea.
Int J Mol Sci. 2022 Feb 26;23(5):2609. doi: 10.3390/ijms23052609.
The hypothalamic arcuate nucleus (Arc) is a central unit that controls the appetite through the integration of metabolic, hormonal, and neuronal afferent inputs. Agouti-related protein (AgRP), proopiomelanocortin (POMC), and dopaminergic neurons in the Arc differentially regulate feeding behaviors in response to hunger, satiety, and appetite, respectively. At the time of writing, the anatomical and electrophysiological characterization of these three neurons has not yet been intensively explored. Here, we interrogated the overall characterization of AgRP, POMC, and dopaminergic neurons using genetic mouse models, immunohistochemistry, and whole-cell patch recordings. We identified the distinct geographical location and intrinsic properties of each neuron in the Arc with the transgenic lines labelled with cell-specific reporter proteins. Moreover, AgRP, POMC, and dopaminergic neurons had different firing activities to ghrelin and leptin treatments. Ghrelin led to the increased firing rate of dopaminergic and AgRP neurons, and the decreased firing rate of POMC. In sharp contrast, leptin resulted in the decreased firing rate of AgRP neurons and the increased firing rate of POMC neurons, while it did not change the firing rate of dopaminergic neurons in Arc. These findings demonstrate the anatomical and physiological uniqueness of three hypothalamic Arc neurons to appetite control.
下丘脑弓状核(Arc)是一个控制食欲的中枢单位,通过整合代谢、激素和神经元传入输入来实现。Agouti 相关蛋白(AgRP)、前阿黑皮素原(POMC)和 Arc 中的多巴胺能神经元分别调节饥饿、饱腹感和食欲的摄食行为。在撰写本文时,这些三种神经元的解剖学和电生理学特征尚未得到深入探讨。在这里,我们使用遗传小鼠模型、免疫组织化学和全细胞膜片钳记录技术来研究 AgRP、POMC 和多巴胺能神经元的整体特征。我们使用标记有细胞特异性报告蛋白的转基因系来确定 Arc 中每个神经元的独特地理位置和内在特性。此外,AgRP、POMC 和多巴胺能神经元对胃饥饿素和瘦素的处理有不同的放电活动。胃饥饿素导致多巴胺能和 AgRP 神经元的放电率增加,而 POMC 神经元的放电率降低。相比之下,瘦素导致 AgRP 神经元的放电率降低和 POMC 神经元的放电率增加,而对 Arc 中的多巴胺能神经元的放电率没有影响。这些发现表明下丘脑 Arc 中的三种神经元在控制食欲方面具有解剖学和生理学上的独特性。