Experience-Dependent Neuroglial Plasticity in Autism Spectrum Disorder

Experience-dependent plasticity involves coordinated changes in neuronal and glial function, but the glial contribution to circuit adaptation in autism spectrum disorder (ASD) remains incompletely understood. Astrocytes monitor synaptic activity and metabolic demand, microglia participate in activity-dependent synaptic remodeling, and oligodendrocyte-lineage cells adjust differentiation and myelination in response to neuronal firing and learning. Human induced pluripotent stem cell models, xenotransplantation studies, postmortem single-cell datasets and genetic models implicate these cells in ASD-associated circuit dysfunction, with causal contributions having been demonstrated for defined phenotypes in experimental systems. In this narrative review, we integrate this evidence with studies of sensory stimulation and deprivation, motor learning and social experience to examine how glia may link repeated activity with durable circuit adaptation. Motor-skill learning requires rapid oligodendrocyte production, whereas juvenile social experience regulates prefrontal oligodendrocyte maturation. Visual stimulation evokes astrocytic Ca2+ responses, and voluntary exercise can restore microglial engulfment of excess synapses in a maternal-immune-activation model. Environmental enrichment includes direct and perturbation-based glial evidence, whereas music provides predominantly associative or cell-nonspecific observations. Fragile X studies connect astrocytic dysfunction with motor learning and sensory responses, but the involvement of glia varies with genotype, circuit and developmental stage. The evidence nevertheless differs substantially across systems. Cell-specific causality has been demonstrated for selected astrocytic, microglial and oligodendroglial mechanisms, whereas human intervention studies remain largely cell-nonspecific. Taken together, these findings support glial participation in experience-dependent plasticity but do not establish glial mediation of human interventions. ASD-associated glial states may therefore modify the response to experience, rather than representing targets whose normalization can be assumed to be beneficial.