Background: Etiology, primary pathology and mechanisms underlying autism spectrum disorders (ASD) are currently unknown. There is no cure for ASD in the foreseeable future, and available treatment options are limited. Recent evidence indicates that abnormal development of neuronal connections and an altered ratio of excitatory versus inhibitory synapses in the brain may underlie certain abnormalities of ASD. Altered size and packing density of neurons in limbic areas including amygdala has also been described in postmortem brains of autism. ASD is characterized by deficits in social interaction for which no specific pharmacological treatment is currently available. However, evidence indicates that group behavioral therapy might be beneficial in certain cases of ASD. Objectives:

Methods: We are presenting a rat model in which pathfinding of cerebral corticopetal fibers are targeted by lesioning the subplate cells of the developing cerebral cortex. Results: Lesioned animals show increased ratio of excitatory:inhibitory synapses in the cerebral cortex, and increased volume of basolateral and lateral subnuclei of the amygdala showing densely packed small neurons. Moreover, lesioned rats show deficits in social interaction. Interestingly, this abnormality is significantly improved by raising rats as lesioned + control pairs in comparison to raising them as lesioned + lesioned pairs. Conclusions: Present rat model may facilitate identifying mechanisms underlying social interaction deficits, and particularly the neurobiological basis of improvement seen in lesioned animals following raising them paired with normal animals.