SAN2020

Autism spectrum disorder (ASD) is a group of pathologies characterized by social impairment and restricted and repetitive behaviors. Our lab has validated a pharmacological model where mice prenatally exposed to Valproic Acid (VPA) express ASD related behaviors, along with a higher glucose metabolism, increased cFos activity, and reduced myelinization in the Piriform Cortex (Pir). The aim of this project is to evaluate whether neuronal activity and myelination in the Pir underlie the differences in sociability. First, to test the hypothesis stating that an increase in the activity of the Pir impairs sociability, we will inject Adeno associated virus (AAV) expressing Designer Receptors Exclusively Activated by Designer Drugs (DREADD´s) bilaterally in this structure, and evaluate sociability after clozapine-N-oxide (CNO) administration. We will use AAV-CaMKIIa-hM3D(Gq)-mCherry to increase the neuronal activity of WT mice, and AAV-CaMKIIa-hM4D(Gi)-mCherry to decrease the activity of VPA animals. Next, to evaluate whether Pir hypomyelination contributes to a lower sociability in VPA mice, we will inject Lysophosphatidylcholine 1% (LPC), a demyelinating agent bilaterally in the Pir and evaluate sociability after 7 days (when Pir myelin loss is already detectable) and 21 days (when spontaneous remyelination has occured). With this approach, we aim to better understand the role of the Pir in the modulation of social behavior in mice.