An oxytocinergic neural pathway that stimulates thermogenic and cardiac sympathetic outflow

Oxytocin alters autonomic functions besides social behaviors. However, the central neuronal links between hypothalamic oxytocinergic neurons and the autonomic nervous system remain unclear. Here we show that oxytocinergic neurons in the rat paraventricular hypothalamic nucleus (PVH), a pivotal site for energy homeostasis, innervate sympathetic premotor neurons in the rostral medullary raphe region (rMR) to stimulate brown adipose tissue (BAT) thermogenesis and cardiovascular functions. Oxytocin receptor stimulation in the rMR evokes BAT thermogenesis and tachycardia. In vivo optogenetic stimulation of the PVH→rMR long-range oxytocinergic pathway, using a virus-mediated system for amplified gene expression in oxytocinergic neurons, not only elicits BAT thermogenic and cardiac responses but also potentiates sympathetic responses evoked by glutamatergic transmission in the rMR. The PVH→rMR oxytocinergic pathway connects the hypothalamic circuit for energy homeostasis to thermogenic and cardiac sympathetic outflow, and, therefore, its defects may cause obesity and impaired thermoregulation, as seen in Prader-Willi syndrome.