Background: Prenatal alcohol exposure (PAE) induces a wide range of neurodevelopmental disabilities grouped under the term fetal alcohol spectrum disorders (FASD). The effects of PAE on brain development are dependent on complex long-lasting neurochemical events, including modification of glutamate receptors. Here, we explored whether PAE may affect the functional connectivity and, further, the molecular composition of the glutamatergic synapses in the prefrontal cortex (PFC) of adolescent mice and its effect on social behaviors.Methods: We generated an in vivo model of PAE, by exposing C57Bl/6 pregnant mice to 10% EtOH during the first gestational period. The offspring were analyzed during adolescence for protein expression, functional cortical connectivity and social behavior.Results: PAE elicited significant modification in the subunit composition of AMPA and NMDA receptors associated to altered expression of Rab proteins, regulators of synaptic trafficking and vesicular recycling. Moreover, PAE significantly decreased the expression of the neurotrophin BDNF and its own receptor TrkB in the PFC, thus altering cortical neuroplasticity. In addition, we observed alterations in cortical functional connectivity measured using widefield fluorescence microscopy, which captures the correlations between the neuronal activity in functional areas distributed on the dorsal cortical mantle. Our molecular and functional results were paralleled by reduced sociability and social memory observed in PAE offspring, without alteration in locomotor activity and hedonic tone.Conclusions: Our study suggest that PAE leads to long-lasting reorganization of the PFC, an effect that could be responsible for the behavioral impairments, thus contributing to further comprehend the pathogenesis of FASD.