P3.31. DIVERGENT EFFECTS OF OXYTOCIN AND RELAXIN-3 SIGNALING IN THE VENTRAL DENTATE GYRUS: A NEURONAL BASIS FOR ANXIETY DISORDERS
Gabriela Stopka1,2, Aleksandra Trenk1, Anna Gugula1, Kinga Przybylska1,2, Patryk Sambak1,2, Anna Blasiak1
1 Department of Neurophysiology and Chronobiology, Institute of Zoology and Biomedical Research, Jagiellonian University, Krakow, Poland
2 Doctoral School of Exact and Natural Sciences, Jagiellonian University, Krakow, Poland
INTRODUCTION: Anxiety disorders are among the most prevalent psychiatric conditions, with the ventral dentate gyrus (vDG) of the hippocampus playing a key role in their pathophysiology. Oxytocin (OXT) and relaxin-3 (RLN3) are crucial neuropeptides that regulate neuronal circuits involved in contextual processing, social interaction, stress, and anxiety-related behaviors. Activation of the OXT/oxytocin receptor (OXTR) system produces anxiolytic effects, while activation of the RLN3/relaxin-3 receptor (RXFP3) system has opposing, anxiogenic actions.
AIM(S): Despite their distinct roles, the interplay between the OXT and RLN3 signaling in key anxiety-related brain regions such as the vDG remains underexplored. This study aimed to examine the influence of OXT and RLN3 on the neuronal activity in the rat vDG, aiming to uncover mechanisms underlying anxiety disorders.
METHOD(S): Viral-based neural tract tracing was used to identify RLN3-positive fibers originating from the nucelus incertus (NI) in the vDG. HiPlex in situ hybridization (ISH) was applied to detect RXFP3 mRNA-expressing cells and assess co-expression with inhibitory neuron markers, including vesicular GABA transporter (vGAT1), somatostatin, and OXTR mRNA. Additionally, whole-cell patch-clamp ex vivo recordings were conducted to examine the effect of OXT alone and in the presence of RLN3 on vDG granule cell activity.
RESULTS: RLN3-positive fibers from the NI innervated both the hilus and inner molecular layer of the vDG in a similar pattern. HiPlex ISH showed RXFP3 mRNA co-expression with vGAT1 and somatostatin, and moderately with OXTR mRNA. Electrophysiological recordings revealed that these neuropeptides altered vDG granule cell activity.
CONCLUSIONS: In summary, our findings suggest that OXT and RLN3 exert opposing effects on neuronal activity in the vDG, which may represent a neuronal substrate for the modulation of stress, anxiety, and social behavior. Moreover, these results highlight the possible role of their interaction in anxiety-related disorders.
FINANCIAL SUPPORT: National Science Centre Poland grant UMO-2023/49/B/NZ4/01885, MiniGrant2023-ID.UJ and RSM2025-ID.UJ U1U/W18/NS/28.20.