CONICET | Buscador de Institutos y Recursos Humanos

Autism is a neurodevelopmental disorder characterized by impaired sociability and stereotypic behaviors. Individuals also have auditory symptoms, i.e. hypersensitivity to loudness of sound with abnormal behavioral reactions to environmental sounds. We hypothesized that there is a developmental critical window in which maturation and consolidation of the neural systems responsible for these symptoms typically occur.The administration of VPA at GD 12.5 results in autism-related behaviors in adulthood. The aim of this work is to characterize early alterations in this model. We found a delay in the apparition of the righting reflex and in the acoustic startle response. To further characterize this last deficit, we measured the auditory brainstem response (ABRs), which reflect synchronized discharges from neurons along the auditory pathway and found an elevated threshold profile at P14-P16 and P21-P23 in VPA mice. This shows that the maturation delay observed leads to a lasting alteration in hearing function. We observed other alterations in the brain at P21: VPA animals show higher GFAP+ density and activated microglia in the hippocampus, but fewer activated microglial cells in thecerebellum.In summary, we found that mice prenatally exposed to VPA show altered physiological responses at the third postnatal week. Current experiments are testing whether this period is a critical period for autism related behaviors.