Striatal Interneuron Imbalance in a Valproic Acid-Induced Model of Autism in Rodents Is Accompanied by Atypical Somatosensory Processing.

Abstract

Autism spectrum disorder (ASD) is characterized by deficits in social interaction and communication, cognitive rigidity, and atypical sensory processing. Recent studies suggest that the basal ganglia, specifically the striatum (NSt), plays an important role in ASD. While striatal interneurons, including cholinergic (ChAT⁺) and parvalbumin-positive (PV⁺) GABAergic neurons, have been described to be altered in animal models of ASD, their specific contribution remains elusive. Here, we combined behavioral, anatomical, and electrophysiological quantifications to explore if interneuron balance could be implicated in atypical sensory processing in cortical and striatal somatosensory regions of rats subjected to a valproic acid (VPA) model of ASD. We found that VPA animals showed a significant decrease in the number of ChAT⁺ and PV⁺ cells in multiple regions (including the sensorimotor region) of the NSt. We also observed significantly different sensory-evoked responses at the single-neuron and population levels in both striatal and cortical regions, as well as corticostriatal interactions. Therefore, selective elimination of striatal PV⁺ neurons only partially recapitulated the effects of VPA, indicating that the mechanisms behind the VPA phenotype are much more complex than the elimination of a particular neural subpopulation. Our results indicate that VPA exposure induced significant histological changes in ChAT⁺ and PV⁺ cells accompanied by atypical sensory-evoked corticostriatal population dynamics that could partially explain the sensory processing differences associated with ASD.