Lectures and seminars Seminar with Laurie Galvan: "Involvement of Striatal PV Interneurons in Autism Spectrum Disorder"

University of Nîmes, Laboratory for Physical and Sports Activities and Psychological Processes: Research on Vulnerabilities, France.

Abstract

Autism spectrum disorders (ASD) are lifelong neurodevelopmental conditions, yet most experimental studies have focused on early developmental stages, leaving the evolution of neural circuit dysfunctions throughout adulthood largely unexplored. Using longitudinal approaches in Cntnap2 and Shank3 mouse models, we show that repetitive behaviors are not static features of ASD but undergo progressive reorganization across adulthood. This behavioral evolution is accompanied by dynamic remodeling of striatal circuits, including alterations in inhibitory synaptic transmission (ex vivo electrophysiology), medium spiny neuron morphology, and network organization, revealing adulthood as an active period of circuit plasticity with important implications for ASD pathophysiology. To uncover the cellular mechanisms underlying these changes, we investigated the role of striatal parvalbumin (PV) interneurons, a neuronal population repeatedly implicated in ASD. We demonstrate that PV interneurons are hyperactive and hyperexcitable in Cntnap2-deficient mice. Importantly, selective inhibition of PV interneurons restores normal behavioral output, establishing a causal link between PV interneuron dysfunction and ASD-related repetitive behaviors. Finally, I will discuss emerging evidence supporting a central role for PV interneurons in the maintenance of EEG signals in humans, opening new opportunities to bridge cellular mechanisms with translational biomarkers in ASD.