id_970. ELECTROPHYSIOLOGICAL AND ANATOMICAL ALTERATIONS OF VENTRAL DENTATE GYRUS CIRCUITRY IN A RAT MODEL OF AUTISM SPECTRUM DISORDER
Aleksandra Nogaj1,2, Kacper Kula1, Aleksandra Trenk1, Anna Guguła1, Kinga Przybylska1,2, Anna Błasiak1
1 Department of Neurophysiology and Chronobiology, Institute of Zoology and Biomedical Research, Jagiellonian University, Krakow, Poland
2 Doctoral School of Exact and Natural Sciences, Faculty of Biology, Jagiellonian University, Krakow, Poland
INTRODUCTION: Autism spectrum disorder (ASD) is characterized by social impairments, anxiety, and disturbances in hippocampal processing. The ventral dentate gyrus (vDG), a region involved in social memory processing and pattern separation, is particularly susceptible to circuit-level imbalance. Alterations in inhibitory interneurons, especially parvalbumin (PV+) and somatostatin (SST+) cells, as well as neuromodulatory inputs to DG may contribute to abnormalities observed in ASD.
AIM(S): The present study examined functional and anatomical changes in vDG neurons in a rat model of ASD, focusing on granule cells, interneuron subtypes, and cells expressing the relaxin-3 (RLN3) receptor-RXFP3.
METHOD(S): ASD-like phenotypes were induced by prenatal valproic acid (VPA) exposure (500 mg/kg, E12.5) in Sprague-Dawley rats. Intrinsic membrane properties and synaptic activity of vDG granule cells were evaluated using whole-cell patch-clamp recordings. Molecular profile of vDG cells was assessed using multiplex RNAscope targeting PV, SST, vGAT1, vGLUT2, and RXFP3 mRNA. Immunohistochemistry was used to assess PV+ and SST+ cell density in vDG and RLN3+ neurons in the nucleus incertus.
RESULTS: Granule cells in VPA-exposed animals displayed enhanced neuronal gain, indicating increased excitability, while passive membrane parameters remained unaffected. Female VPA rats showed a reduced density of SST+ interneurons, whereas PV+ interneuron numbers were not affected. RXFP3 expression was largely confined to vGAT1-positive neurons, with frequent co-expression in SST+ cells.
CONCLUSIONS: Our findings demonstrate heightened excitability of vDG granule cells accompanied by selective vulnerability of SST interneurons in VPA females. RXFP3 expression in SST+ and other inhibitory vDG neurons suggests that RLN3 signaling may influence inhibitory networks and contribute to hippocampal dysfunction in ASD.
FINANCIAL SUPPORT: National Science Centre, Poland (UMO-2023/49/B/NZ4/01885; UMO2024/53/N/NZ4/03919)