O-245 Monitoring oxytocin release in vivo during female sexual behavior using a genetically encoded sensor

Abstract

Abstract Study question To investigate if the release of oxytocin (OT) in the medial prefrontal cortex (mPFC) fluctuates during discrete phases of female sexual behavior. Summary answer Using a highly sensitive OT-specific genetically encoded sensor, we have recorded behavioral phase-specific OT release in mPFC in freely moving mice. What is known already OT has been reported to participate in the regulation of sexual behavior of both male and female mice. OT activated mPFC neurons by increasing their firing activity. Loss of function studies indicated that pharmacological or genetic ablation of OT signaling in mPFC largely disrupts female sociosexual interest in male mice. OT action is indispensable in female sociosexual behavior, however, its release dynamics have never been recorded before due to technical difficulties. We have developed a highly sensitive OT-specific G-protein-coupled receptor activation-based sensor (OT1.0), and recorded intracellular OT release in behaving mice on the millisecond time-scale. Study design, size, duration Eight C57BJ/6N mice were divided into two groups (n = 4 per group). Intracellular viral transduction with OT1.0 or OT1.0mut vectors was administrated to each group. After viral transduction, 3 weeks were waited to allow sufficient viral expression. Participants/materials, setting, methods After anesthetization, AAVs encoding hSyn-OT1.0 or hSyn-OT1.0mut were injected into the left mPFC of adult female wild-type C57BJ/6N mice; Optical fibers were implanted into the mPFC 3 weeks after AAV injection. The animal’s sexual behaviors were recorded and annotated, while a fiber photometry system was used to record fluorescence signals in the mPFC, using a 470-nm laser at 50 μW for OT1.0 or OTmut. Main results and the role of chance To investigate the dynamics of OT release in mPFC during female sexual behavior, we recorded OT1.0 fluorescence in behaving female mice using fiber photometry. In mPFC of female mice, increases in OT1.0 fluorescence were first observed during the sniffing stage (with rise and decay time constants (T1/2) of 0.4 s and 1.4 s, respectively ). After ejaculation of male mice, mPFC OT1.0 signals of the female mice increased significantly with rise and decay time constants (T1/2) of 0.5 s and 1.5 s, respectively. As a negative control, fluctuation of fluorescence was not observed during any phase of sexual behavior in mice expressing OT1.0mut, suggesting the specificity of the signals measured in mice expressing OT1.0. Limitations, reasons for caution The OT dynamics in mPCF during female sexual behaviors are only recorded in mice. Clinical trials and imaging studies are required to substantiate the therapeutic role of OT in human subjects. Wider implications of the findings This study is likely to deepen our understanding of the role of OT in modulating female sociosexual behavior, which provides more evidence suggesting OT’s potential therapeutic potential in treating sexual dysfunctions. Trial registration number not applicable