CONICET | Buscador de Institutos y Recursos Humanos

Autism spectrum disorders (ASD) are characterized by impairments in social interaction and repetitive-stereotyped behaviors. Although increased cortical excitatory-inhibitory (E-I) ratio has been described in ASD patients, results in the hippocampus are not conclusive. By employing the valproic acid (VPA) model of ASD, we reported in the hippocampus of VPA rats a reduction in the synaptic marker synaptophysin along with an increased expression ratio in the adhesive/non-adhesive forms of the neural cell adhesion molecule (NCAM). . This study aimed to evaluate E-I balance, synapse formation and remodeling in primary hippocampal neurons either from VPA or control postnatal male pups. Synaptic markers were evaluated by immunocytochemistry and WB. At DIV14, hippocampal neurons from VPA animals displayed a reduced dendritic tree (reduced MAP-2 area), a reduced number of glutamatergic synapses (decreased vGLUT puncta number and area) and NMDA receptor clusters (decreased NR1 puncta number and individual puncta area) but no changes in gabaergic synapses (conserved GAD-67 puncta number). These neurons also exhibited reduced number of functional synapses (FM4-64) which contained smaller vesicular pools with preserved unloading kinetics; total NCAM expression increased while its non-adhesive form (PSA-NCAM)decreased. While in neurons from control animals glutamate exposure (5µM-3min) induced an NMDA-dependent dendritic retraction and synapse number reduction, neurons from VPA animals only exhibited dendritic retraction. Our results indicate that neurons from VPA animals form fewer glutamatergic synapses with a more adhesive and resistant profile to synaptic remodeling, suggesting an underlying mechanism that would contribute to reduced structural synaptic plasticity in the hippocampus.