In Utero Exposure to Anti-Caspr2 Antibody Disrupts Parvalbumin Interneuron Function in the Hippocampus

Abstract

Autism Spectrum Disorder (ASD) is a complex neurodevelopmental condition characterized by deficits in communication and social interaction and may stem from an imbalance between excitatory and inhibitory (E/I) signaling in neural circuits. Parvalbumin-expressing (PV+) interneurons are crucial for maintaining E/I balance and regulating network oscillations. Alterations in the number of PV+ interneurons or reductions in PV expression have been observed in both the postmortem brains of individuals with ASD and in animal models, including those induced by in utero exposure to maternal brain-reactive antibodies. In this study, we investigate the impact of in utero exposure to maternal anti-Caspr2 IgG on PV+ interneuron development and function in the hippocampus. Our results demonstrate a selective reduction in PV+ interneurons and perisomatic inhibitory synapses in the hippocampal CA1 region of juvenile and adult male offspring exposed in utero to anti-Caspr2 antibodies compared to controls. Additionally, local field potential (LFP) recordings from these mice show increased gamma power and altered neuronal firing patterns during social interactions, indicating functional impairments in inhibitory circuitry. These findings highlight the consequences of exposure to maternal anti-Caspr2 antibodies on PV+ interneuron development and function, providing insights into the neurobiological mechanisms underlying ASD associated behavioral phenotypes.