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31.12.07 - Altered neocortical microcircuitry in the valproic acid rat model of autism. Thesis EPFL, n° 3701 (2006). Dir.: Prof. H. Markram

"For her major contribution to our understanding of the molecular, cellular and synaptic alterations in Autism"

Altered Neocortical Microcircuitry in the Valproic Acid Rat Model of Autism.

Autism is a wide spectrum disorder with early childhood onset, affecting general cognitive capabilities and, in particular, complex information processing. The goal of this PhD project was to get a better understanding of the neocortical microcircuitry alterations in autism, using the valproic aicd (VPA) rat model of autism.

Previous studies explored the results of prenatal VPA exposure in rats and found similar gross abnormalities and behavioral symptoms to those in autism.

We examined the postnatal effects of embryonic exposure to VPA on the microcircuit properties of juvenile rat neocortex using in vitro electrophysiology. We found that prenatal VPA exposure causes a significant increase of more than 50% of the local connectivity formed by pyramidal neurons, and that the neocortical network becomes hyper-reactive to external stimuli. Two possible compensatory mechanisms following the hyperconnectivity were identified: reduced neuronal excitability and decreased synaptic connection strength. The thesis results also illustrate how NMDA receptors are significantly enhanced in the rat model and how this enhancement is associated with an increased plasticity.

These alterations may account for some of the core symptoms in autism, such as aberrant reactions to sensory stimulation, altered attention and the unusual learning and memory capabilities of some autistic children.

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