Imbalance of circuit plasticity and consolidation in autism model marmosets is adjusted by oxytocin administration

Abstract

AbstractImpairments in the experience-dependent elaboration of neural circuits are assumed to underlie autism spectrum disorder (ASD). However, the phenotype underlying synaptic plasticity is poorly understood. Here, we used a valproic acid–induced ASD marmoset model and in vivo two-photon microscopy to investigate the structural dynamics of dendritic spines in the dorsomedial prefrontal cortex, which is involved in ASD core symptoms. In model marmosets compared to controls, spine turnover was upregulated and spines were actively generated in clusters. Clustered emerging spines were predominant in carryover of generated spines in the model marmosets. Presynaptic boutons of local axons, but not long-range commissural axons, showed hyperdynamic turnover. Furthermore, nasal oxytocin administration reduced the clustered emergence of spines. Finally, we confirmed the high molecular conformity of adult animal models with human ASD. Our study suggests that an altered balance between synaptic plasticity and consolidation underlies ASD, and may be a potential therapeutic target.