The State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, and the Institutes of Brain Science, Fudan University, Shanghai, 200032, China.
The State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, and the Institutes of Brain Science, Fudan University, Shanghai, 200032, China
J Neurosci. 2022 Apr 6;42(14):2885-2904. doi: 10.1523/JNEUROSCI.2494-21.2022. Epub 2022 Feb 23.
Oxytocin (OXT) neurons in paraventricular nucleus of hypothalamus (PVN) are involved in modulating multiple functions, including social, maternal, feeding, and emotional related behaviors. PVN OXT neurons are canonically classified into magnocellular (Magno) and parvocellular (Parvo) subtypes. However, morpho-electric properties and the diversity of PVN OXT neurons are not well investigated. In this study, we profiled the morpho-electric properties of PVN OXT neurons by combining transgenic mice, electrophysiological recording, morphologic reconstruction, and unsupervised clustering analyses. Total 224 PVN OXT neurons from 23 mice were recorded and used for analyses in this study, and 29 morpho-electric parameters were measured. Magno and Parvo OXT neurons have prominent differences in their morpho-electric features, and PVN OXT neurons in male and female mice share similar neuronal properties. Some morpho-electric features of PVN OXT neurons, especially Magno neurons, exhibit significant diverse changes along the rostral-caudal axis. Furthermore, we find that PVN OXT neurons are classified into at least six subtypes based on their morpho-electric properties via unsupervised clustering. Only one Magno-Parvo mixed subtype in posterior PVN subregion, but not the other five subtypes, showed significant neuronal activity change in different feeding conditions. Our study supports the diversity of PVN OXT neurons and subtle neuron classification will promote excavating the functions of oxytocinergic system. Oxytocin (OXT) is well known for its function in labor induction, but it also plays multiple roles in social, feeding, and emotional behaviors via modulating different brain regions. Paraventricular nucleus of hypothalamus (PVN) OXT neurons are traditionally classified into magnocellular and parvocellular. However, functional and single-cell transcriptomic studies indicate that OXT neurons should be further classified. Here, we thoroughly investigated the morpho-electric properties and spatial distribution of PVN OXT neurons, and find that OXT neurons have at least six subtypes based on their morpho-electric features. Among these six subtypes, only one magnocellular-parvocellular mixed subtype, which are distributed in the posterior PVN subregion, change their activities with different feeding states. Our study uncovers the diversity of PVN OXT neurons and suggests the necessary of subtle neuronal classification.
下丘脑室旁核 (PVN) 的催产素 (OXT) 神经元参与调节多种功能，包括社会、母性、进食和情绪相关行为。PVN OXT 神经元通常分为大细胞 (Magno) 和小细胞 (Parvo) 亚型。然而，PVN OXT 神经元的形态电特性和多样性尚未得到很好的研究。在这项研究中，我们通过结合转基因小鼠、电生理记录、形态重建和无监督聚类分析来描绘 PVN OXT 神经元的形态电特性。总共从 23 只小鼠中记录了 224 个 PVN OXT 神经元，并在本研究中用于分析，测量了 29 个形态电参数。Magno 和 Parvo OXT 神经元在形态电特征上有显著差异，雄性和雌性小鼠的 PVN OXT 神经元具有相似的神经元特性。PVN OXT 神经元的一些形态电特征，特别是 Magno 神经元，沿头尾轴表现出显著的变化。此外，我们通过无监督聚类发现，根据形态电特性，PVN OXT 神经元至少可分为六种亚型。只有后 PVN 亚区的一种 Magno-Parvo 混合亚型，而不是其他五种亚型，在不同的进食条件下表现出明显的神经元活动变化。我们的研究支持 PVN OXT 神经元的多样性，而微妙的神经元分类将促进挖掘催产素能系统的功能。催产素 (OXT) 以其在分娩诱导中的作用而闻名，但它通过调节不同的大脑区域，在社会、进食和情绪行为中也发挥着多种作用。下丘脑室旁核 (PVN) 的催产素神经元传统上分为大细胞和小细胞。然而，功能和单细胞转录组学研究表明，催产素神经元应该进一步分类。在这里，我们彻底研究了 PVN OXT 神经元的形态电特性和空间分布，发现 OXT 神经元至少可根据其形态电特征分为六种亚型。在这六种亚型中，只有一种大细胞-小细胞混合亚型，分布在后 PVN 亚区，其活动随不同的进食状态而变化。我们的研究揭示了 PVN OXT 神经元的多样性，并表明需要进行微妙的神经元分类。
