Skip to Main content Skip to Navigation
Journal articles

Abnormal network activity in a targeted genetic model of human double cortex.

Abstract : In human patients, cortical dysplasia produced by Doublecortin (DCX) mutations lead to mental retardation and intractable infantile epilepsies, but the underlying mechanisms are not known. DCX(-/-) mice have been generated to investigate this issue. However, they display no neocortical abnormality, lessening their impact on the field. In contrast, in utero knockdown of DCX RNA produces a morphologically relevant cortical band heterotopia in rodents. On this preparation we have now compared the neuronal and network properties of ectopic, overlying, and control neurons in an effort to identify how ectopic neurons generate adverse patterns that will impact cortical activity. We combined dynamic calcium imaging and anatomical and electrophysiological techniques and report now that DCX(-/-)EGFP(+)-labeled ectopic neurons that fail to migrate develop extensive axonal subcortical projections and retain immature properties, and most of them display a delayed maturation of GABA-mediated signaling. Cortical neurons overlying the heterotopia, in contrast, exhibit a massive increase of ongoing glutamatergic synaptic currents reflecting a strong reactive plasticity. Neurons in both experimental fields are more frequently coactive in coherent synchronized oscillations than control cortical neurons. In addition, both fields displayed network-driven oscillations during evoked epileptiform burst. These results show that migration disorders produce major alterations not only in neurons that fail to migrate but also in their programmed target areas. We suggest that this duality play a major role in cortical dysfunction of DCX brains.
Document type :
Journal articles
Complete list of metadata

Cited literature [55 references]  Display  Hide  Download
Contributor : Roman Tyzio Connect in order to contact the contributor
Submitted on : Wednesday, May 12, 2010 - 4:55:13 PM
Last modification on : Tuesday, October 19, 2021 - 10:50:38 PM
Long-term archiving on: : Thursday, September 16, 2010 - 1:43:02 PM


Publisher files allowed on an open archive




James B. Ackman, Laurent Aniksztejn, Valérie Crépel, Hélène Becq, Christophe Pellegrino, et al.. Abnormal network activity in a targeted genetic model of human double cortex.. Journal of Neuroscience, Society for Neuroscience, 2009, 29 (2), pp.313-27. ⟨10.1523/JNEUROSCI.4093-08.2009⟩. ⟨inserm-00483164⟩



Record views


Files downloads