Oxytocin activation of paraventricular thalamic neurons promotes feeding motivation to attenuate stress-induced hypophagia

The neuropeptide oxytocin (OT) regulates important brain functions including feeding through activating OT receptors in multiple brain areas. Both OT fibers and OT receptors have been reported in the paraventricular thalamus (PVT), an area that was revealed to be important for the control of emotion, motivation, and food intake. However, the function and modulation of PVT OT signaling remain unknown. Here, we used a progressive ratio (PR) schedule of reinforcement to examine the role of PVT OT signaling in regulating the motivation for food and patch-clamp electrophysiology to study the modulation of OT on PVT neurons in brain slices. We demonstrate that PVT OT administration increases active lever presses to earn food rewards in both male and female mice under PR trials and OT receptor antagonist atosiban inhibits OT-induced increase in motivated lever presses. However, intra-PVT OT infusion does not affect food intake in normal conditions but attenuates hypophagia induced by stress and anxiety. Using patch-clamp recordings, we find OT induces long-lasting excitatory effects on neurons in all PVT regions, especially the middle to posterior PVT. OT not only evokes tonic inward currents but also increases the frequency of spontaneous excitatory postsynaptic currents on PVT neurons. The excitatory effect of OT on PVT neurons is mimicked by the specific OT receptor agonist [Thr4, Gly7]-oxytocin (TGOT) and blocked by OT receptor antagonist atosiban. Together, our study reveals a critical role of PVT OT signaling in promoting feeding motivation to attenuate stress-induced hypophagia through exciting PVT neurons.