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Original Research ARTICLE

Hyper-connectivity and hyper-plasticity in the medial prefrontal cortex in the valproic acid animal model of autism

Tania Rinaldi^1,2, Catherine Perrodin¹ and Henry Markram^1*

Brain Mind Institute, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland

Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA, USA

The prefrontal cortex has been extensively implicated in autism to explain deficits in executive and other higher-order functions related to cognition, language, sociability and emotion. The possible changes at the level of the neuronal microcircuit are however not known. We studied microcircuit alterations in the prefrontal cortex in the valproic acid rat model of autism and found that the layer 5 pyramidal neurons are connected to significantly more neighbouring neurons than in controls. These excitatory connections are more plastic displaying enhanced long-term potentiation of the strength of synapses. The microcircuit alterations found in the prefrontal cortex are therefore similar to the alterations previously found in the somatosensory cortex. Hyper-connectivity and hyper-plasticity in the prefrontal cortex implies hyper-functionality of one of the highest order processing regions in the brain, and stands in contrast to the hypo-functionality that is normally proposed in this region to explain some of the autistic symptoms. We propose that a number of deficits in autism such as sociability, attention, multi-tasking and repetitive behaviours, should be re-interpreted in the light of a hyper-functional prefrontal cortex.

Keywords:

autism, microcircuit, synaptic connectivity, synaptic plasticity, in vitro electrophysiology, hyper-connectivity, hyper-plasticity, hyper-functionality

Citation:

Rinaldi T, Perrodin C and Markram H (2008). Hyper-connectivity and hyper-plasticity in the medial prefrontal cortex in the valproic acid animal model of autism. Front. Neural Circuits 2:4. doi: 10.3389/neuro.04.004.2008

Received:

25 May 2008;

Paper pending published:

05 August 2008;

Accepted:

10 October 2008;

Published online:

29 October 2008.

Edited by:

Yves Fregnac, UNIC, CNRS, France

Reviewed by:

Zoltan Nusser, Institute of Experimental Medicine, Hungary
Bruno Cauli, Universite Pierre et Marie Curie, France

© 2008 Rinaldi, Perrodin and Markram. This is an open-access article subject to an exclusive license agreement between the authors and the Frontiers Research Foundation, which permits unrestricted use, distribution, and reproduction in any medium, provided the original authors and source are credited.

*Correspondence:

Henry Markram, Brain Mind Institute, Ecole Polytechnique Fédérale de Lausanne (EPFL), CH-1015 Lausanne, Switzerland. e-mail: henry.markram@epfl.ch