INTRODUCTION: Autism spectrum disorder (ASD) is a neurodevelopmental condition associated with social deficits, anxiety, and altered hippocampal processing. The dentate gyrus (DG), particularly its ventral region (vDG), is implicated in social memory and pattern separation. Dysregulation of vDG GABAergic interneurons, especially parvalbumin (PV+) and somatostatin (SST+) cells, may underlie functional alterations observed in ASD. These interneuron populations are key regulators of granule cell excitability and neurodevelopment.

AIM(S): Therefore, the aim of this study was to investigate the electrophysiological and anatomical characteristics of vDG interneurons in a rat model of ASD.

METHOD(S): Therefore, we investigated the anatomical and electrophysiological features of the vDG neurons in male and female Sprague-Dawley rats using control animals and a valproic acid (VPA; 500 mg/kg, E12.5)-induced rat model of ASD. Immunohistochemistry was used to assess PV+ and SST+ cell density in vDG. Whole-cell patch-clamp recordings from granule cells were conducted in hippocampal slices to assess intrinsic membrane properties and inhibitory synaptic transmission.

RESULTS: Our preliminary results indicate that VPA exposure specifically affects granule cells excitability, evidenced by increased neuronal gain, while basic membrane properties and inhibitory post-synaptic currents remained unchanged. Importantly, we demonstrated that the observed effect was not depended on the number of PV+ or SST+ interneurons.

CONCLUSIONS: These findings suggest specific alternation in the intrinsic vDG granule cell excitability, without corresponding changes in GABAergic neurotransmission in ASD. Ongoing studies aim to elucidate the underlying neuronal mechanism of these effects

FINANCIAL SUPPORT: National Science Centre, Poland (UMO-2023/49/B/NZ4/01885; UMO-2024/53/N/NZ4/03919) RSM 2025: U1U/W18/NS/28.19 - ID.UJ