The oxytocin system regulates tearing

Tears are an exocrine physiological fluid secreted onto the ocular surface from the lacrimal apparatus in all mammals. Limited research has been conducted on the functional neuronal circuitry of tear production. In particular, the neuronal mechanisms of emotional tearing, which is a physiological reaction harmonized with enhanced emotional arousal and assumed to be unique to humans, remain unclear. We identified that the oxytocin neurons in the paraventricular hypothalamus is functionally projected to the oxytocin receptor-expressing neurons in the lacrimation center of the superior salivatory nucleus. Optogenetic activation or inhibition of these neurons and/or receptors can modulate the superior salivatory nucleus dependent tear secretion mediated through oxytocin. Moreover, we identified that maternal behavior, nociceptive behavior stimulation, and aversive memory retrieval are linked to tearing in mice, and that these emotional linked tearing are suppressed by optogenetic inhibition of the corresponding oxytocin system. Thus, tearing could be regulated through functional connections between central oxytocin systems in the paraventricular hypothalamus and the superior salivatory nucleus. ### Competing Interest Statement Kazuo Tsubota is the CEO of Tsubota Laboratory, Inc., Tokyo, Japan, a company developing treatment, prevention, and medical devices for dry eyes. The remaining authors declare that there is no conflict of interest that could affect the impartiality of the research reported.