Amy A. Worth ¹ Claire H. Feetham ¹ Nicole A. Morrissey ² Simon M. Luckman ^1*

• ¹ Faculty of Life Sciences, The University of Manchester, Manchester, United Kingdom
• ² University of Copenhagen, Copenhagen, Capital Region of Denmark, Denmark

The part played by oxytocin and oxytocin neurons in the regulation of food intake is controversial. There is much pharmacological data to support a role for oxytocin notably in regulating sugar consumption, however, several recent experiments have questioned the importance of oxytocin neurons themselves.Methods: Here we use a combination of histological and chemogenetic techniques to investigate the selective activation or inhibition of oxytocin neurons in the hypothalamic paraventricular nucleus (Oxt PVH ). We then identify a pathway from Oxt PVH neurons to the bed nucleus of the stria terminalis using the cell-selective expression of channel rhodopsin.Oxt PVH neurons increase their expression of cFos after both physiological (fast-induced refeeding or oral lipid) and pharmacological (systemic administration of cholecystokinin or lithium chloride) anorectic signals. Chemogenetic activation of Oxt PVH neurons is sufficient to decrease freefeeding in Oxt Cre:hM3Dq mice, while inhibition in Oxt Cre:hM4Di mice attenuates the response to administration of cholecystokinin. Activation of Oxt PVH neurons also increases energy expenditure and core-body temperature, without a significant effect on locomotor activity. Finally, the selective, optogenetic stimulation of a pathway from Oxt PVH neurons to the bed nucleus of the stria terminalis reduces the consumption of sucrose.Our results support a role for oxytocin neurons in the regulation of whole-body metabolism, including a modulatory action on food intake and energy expenditure. Furthermore, we demonstrate that the pathway from Oxt PVH neurons to the bed nucleus of the stria terminalis can regulate sugar consumption.