Morpho-Electric Properties and Diversity of Oxytocin Neurons in Paraventricular Nucleus of Hypothalamus in Female and Male Mice

Abstract

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.SIGNIFICANCE STATEMENT 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.

Keywords: PVN; classification; feeding; morpho-electric properties; oxytocin.