Researchers at the Institute for Neurosciences (IN), a joint center of the Spanish National Research Council (CSIC) and Miguel Hernández University of Elche (UMH), have identified a molecular mechanism that regulates oxytocin release in the brain. The study, published in Communications Biology, explores how this hormone influences social behavior by maintaining what researchers call a "social tone."
Oxytocin is known for its role in emotional bonding and social regulation. Unlike neurotransmitters such as glutamate or GABA, which are released quickly from neuronal axons, oxytocin is a neuropeptide that can also be released from the cell body and dendrites. This type of release is slower and affects larger areas of the brain.
"We knew that oxytocin is released within the brain from compartments other than the axon, but we had limited understanding of how this process is regulated," said Sandra Jurado, head of the Synaptic Neuromodulation Laboratory at IN CSIC-UMH. "Our work focuses precisely on understanding the mechanisms that enable this slow and sustained release, which likely prepares the brain for social interaction," she added.
The team identified SNAP-47 as an essential protein involved in transporting and releasing oxytocin from hypothalamic neurons—the region where this hormone is produced. SNAP-47 belongs to a family of proteins called SNAREs, which help vesicles fuse with cell membranes to release chemical signals.
This mechanism differs from how oxytocin enters the bloodstream via axonal release. Instead, within the brain itself, oxytocin affecting social behavior comes mainly from soma and dendrite release—a process independent of axonal pathways.
To investigate further, researchers used both cultured neurons and mice models. They reduced SNAP-47 expression to observe effects on vesicular trafficking and oxytocin release. Genetic manipulations targeted specifically at oxytocin-producing neurons confirmed their findings in animals.
Reducing SNAP-47 disrupted oxytocin release from soma and dendrites but did not affect classical axonal mechanisms. Mice with lower SNAP-47 levels still showed sociability; however, their interactions were shorter and less robust.
"The effects are subtle, but highly revealing," Jurado explained. "This is not a complete loss of sociability, but rather a fine-tuning of the quality of interactions. This suggests that this release pathway maintains a basal level of oxytocin that primes the brain to respond appropriately to social stimuli."
According to co-author Aznar: "It represents a basal tone that does not trigger strong responses on its own, but that shapes how we react when a relevant social stimulus appears."
The research expands knowledge about hormonal signaling in the brain and may lead to new studies into neuropsychiatric disorders involving oxytocin dysfunctions. "The next step will be to identify the remaining components of this molecular machinery and understand how the different modes of oxytocin release are coordinated to produce a coherent response," Jurado concluded.
Funding came from several sources including Spain’s State Research Agency–Ministry of Science, Innovation and Universities; Prometeo Programme (Generalitat Valenciana); and Severo Ochoa Programme for Centres of Excellence.
