Summary: A newly developed fluorescent sensor is able to detect oxytocin in living animals.
Source: Osaka University
Twinkling lights make a city view all the more beautiful at night, and may evoke feelings of romance and happiness. But what do those feelings look like inside the brain?
Recently, researchers in Japan demonstrated that the power of light may also be harnessed to monitor release of the “happy hormone” oxytocin (OT), a peptide produced in the brain that is associated with feelings of happiness and love.
In a new study published in Nature Methods, researchers led by Osaka University reported their development of a novel fluorescent sensor for the detection of OT in living animals. OT plays an important role in a variety of physiological processes, including emotion, appetite, childbirth, and aging.
Impairment of OT signaling is thought to be associated with neurological disorders such as autism and schizophrenia, and a better understanding of OT dynamics in the brain may provide insight into these disorders and contribute to potential avenues of treatment.
Previous methods to detect and monitor OT have been limited in their ability to accurately reflect dynamic changes in extracellular OT levels over time. Thus, the Osaka University-led research team sought to create an efficient tool to visualize OT release in the brain.
“Using the oxytocin receptor from the medaka fish as a scaffold, we engineered a highly specific, ultrasensitive green fluorescent OT sensor called MTRIAOT,” says lead author of the study, Daisuke Ino.
“Binding of extracellular OT leads to an increase in fluorescence intensity of MTRIAOT, allowing us to monitor extracellular OT levels in real time.”
The research team performed cell culture analyses to examine the performance of MTRIAOT. Subsequent application of MTRIAOT in the brains of living animals allowed for the successful measurement of OT dynamics using fluorescence recording techniques.
“We examined the effects of potential factors that may affect OT dynamics, including social interaction, anesthesia, feeding, and aging,” says Ino.
The research team’s analyses revealed variability in OT dynamics in the brain that was dependent on the behavioral and physical conditions of the animals. Interactions with other animals, exposure to anesthesia, food deprivation, and aging all corresponded with specific patterns of brain OT levels.
These findings indicate that MTRIAOT may serve as a useful tool to enhance our understanding of OT dynamics in the brain. Because abnormalities in OT signaling are thought to be associated with mental disorders, this tool may pave the way for the development of novel therapeutics for the treatment of these diseases.
Additionally, the researchers found that the MTRIA backbone used to engineer the OT sensor may also serve as a scaffold to create sensors for other important brain hormones and neurotransmitters.
A fluorescent sensor for real-time measurement of extracellular oxytocin dynamics in the brain
Oxytocin (OT), a hypothalamic neuropeptide that acts as a neuromodulator in the brain, orchestrates a variety of animal behaviors.
However, the relationship between brain OT dynamics and complex animal behaviors remains largely elusive, partly because of the lack of a suitable technique for its real-time recording in vivo.
Here, we describe MTRIAOT, a G-protein-coupled receptor-based green fluorescent OT sensor that has a large dynamic range, suitable affinity, ligand specificity for OT orthologs, minimal effects on downstream signaling and long-term fluorescence stability.
By combining viral gene delivery and fiber photometry-mediated fluorescence measurements, we demonstrate the utility of MTRIAOT for real-time detection of brain OT dynamics in living mice.
MTRIAOT-mediated measurements indicate variability of OT dynamics depending on the behavioral context and physical condition of an animal. MTRIAOT will likely enable the analysis of OT dynamics in a variety of physiological and pathological processes.