Paraventricular oxytocin neurons impact energy intake and expenditure: projections to the bed nucleus of the stria terminalis reduce sucrose consumption.

Background: 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). We then identify a pathway from Oxt neurons to the bed nucleus of the stria terminalis using the cell-selective expression of channel rhodopsin.

Results: Oxt neurons increase their expression of cFos after both physiological (fast-induced re-feeding or oral lipid) and pharmacological (systemic administration of cholecystokinin or lithium chloride) anorectic signals. Chemogenetic activation of Oxt neurons is sufficient to decrease free-feeding in mice, while inhibition in mice attenuates the response to administration of cholecystokinin. Activation of Oxt 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 neurons to the bed nucleus of the stria terminalis reduces the consumption of sucrose.

Conclusion: 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 neurons to the bed nucleus of the stria terminalis can regulate sugar consumption.