Altered neocortical microcircuitry in the valproic acid rat model of autism

摘要: Autism is a wide-spectrum disorder with early childhood onset, affecting general cognitive capabilities and, in particular, complex information processing. Although interesting directions of research start to appear, the precise causes and resulting brain alterations have not been elucidated yet. The goal this project get better understanding neocortical microcircuitry autism, using valproic acid (VPA) rat model autism. Exposure VPA can cause several teratogenic effects, including autism human if exposure occurs during third week gestation. Previous studies explored results prenatal rats found similar gross abnormalities those such as diminished number Purkinje cells. Behavioural further showed that core symptoms, impairment social interactions higher sensitivity sensory stimulation, are also present VPA-treated rats. We examined postnatal effects embryonic on properties juvenile neocortex vitro electrophysiology. injection significant increase more than 50% local connectivity formed by pyramidal neurons somatosensory cortex, network becomes hyper-reactive external stimuli. identify two possible compensatory mechanisms may follow observed hyperconnectivity: reduced excitability decreased magnitude for individual synaptic connections. illustrate how NMDA receptors significantly enhanced enhancement associated an increased plasticity neocortex. Both somatosensorial prefrontal cortex exhibit plasticity, suggesting brains VPA-exposed In addition, we show multi-electrode array stimulation lateral amygdala reveals plasticity. These account some symptoms spectrum disorders. For example, hyperconnectivity could underlie aberrant reactions altered attention. Also, mediated transmission explain unusual learning memory autistic children. Finally, propose hyper-plastic underlies abnormal fear processing animal speculate be pathology which give rise behavioural impairments resistance rehabilitation.