The brain is ruled by the interactions of chemicals and receptors. However, new research emphasizes that those reactions often radiate beyond the brain, affecting the body’s physiological processes as well. 

A mouse study published Oct. 9 in the journal Cell identified a never-before-seen class of interneurons, a nerve cell that links other nerve cells, which produce the receptor for oxytocin. Oxytocin, a neurotransmitter sometimes dubbed the ‘love hormone,’ influences social interaction by facilitating trust and attachment between individuals and can also play a role in sexual arousal. 

Silencing this new interneuron specifically in the part of the brain responsible for forming emotional adaptive responses caused female mice to lose interest in their male counterparts during the most sexually receptive phase of their reproductive cycles.

Neurons in many parts of the brain express receptors for oxytocin, which is secreted by the pituitary gland but can also be triggered by external stimuli such as touch and certain types of sounds and smells.

To understand the role these neurons play in the complex social behaviors moderated by oxytocin, researchers measured loss of interest in male reproductive partners in three groups of female mice. Among these were a group whose oxytocin receptor-expressing gene was deleted, another whose newly found population of interneurons was suppressed and a control group infused with an antagonist to their oxytocin-expressing gene. 

The results overlapped between groups, suggesting the circuit made up of the novel interneurons is used by external social stimuli that trigger oxytocin production to help adapt behaviors to changing social situations. During diestrus, the reproductive phase following the time when females are sexually receptive, the mice did not experience a deficit in bonding.

“In this study, [the lead author] characterized broader classes of interneurons that are present in the cerebral cortex looking for markers and molecules that would be expressed in smaller, more specific populations,” said Nathaniel Heintz, co-author of the study, professor in the Laboratory of Molecular Biology at The Rockefeller University in New York and Howard Hughes Medical Institute investigator. 

It has been known for more than 100 years that there are likely more than 300 types of neurons in the nervous system, according to Heintz. Comparative analysis of the broad classes characterized in the study led to the identification of the very small subclass of interneurons that express the oxytocin receptor. 

“I was not really looking for oxytocin-responsive interneurons,” said Miho Nakajima, a postdoctoral fellow at New York University’s Halassa Laboratory and lead author of the study. “I was looking for new cell types in the cortex.”

Nakajima said her hypothesis for why the female mice may experience this sociosexual deficit during estrus—when their receptor-expressing interneurons are inhibited—is that when they have the opportunity to become pregnant, female mice seek information about nearby males. Oxytocin is known to make humans more sensitive to emotions, and during their fertile times, there is a tendency for women to pick up on nonverbal cues from potential partners.

“That [might be] why these neurons become very important in the prefrontal cortex,” Nakajima said. “[The mice] are trying to collect all of the information they can.”

Karen Parker, assistant professor in the Department of Psychiatry and Behavioral Science at Stanford University, said beginning in the 1970s, researchers hypothesized that oxytocin may have been involved not only in organizing some of the physiological events associated with motherhood, such as uterine contractions and lactation, but also with turning on mothering instincts and solidifying social bonds in mammals.

“There have been multiple decades’ worth of work showing that oxytocin is not only involved in the onset of maternal care but in a variety of social functions, including parenting behavior,” she said.

According to Parker, in certain species that form socially monogamous bonds, such as the prairie vole, oxytocin is involved in forming partner preference. Human studies show that it plays a role in a variety of different social functions, including social learning, memory and cognition.

The finding shows how analysis of cell populations and molecular pathways within them can improve the understanding of nervous system regulation, Heintz said.

“Most people understand that when someone is under stress, their behavior is quite different than when they’re not,” Heintz said. “This concept of internal modulation of behavioral states is illustrated by the effects of oxytocin on social behavior. Behaviors are both context-dependent and physiologically dependent. Your internal physiology and your external experience can be important for behavior modulation.”