Abnormal network activity in a targeted genetic model of human double cortex. - Inserm - Institut national de la santé et de la recherche médicale Accéder directement au contenu
Article Dans Une Revue Journal of Neuroscience Année : 2009

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

Résumé

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.
Fichier principal
Vignette du fichier
2009-Ackman.pdf (1.68 Mo) Télécharger le fichier
Origine : Fichiers éditeurs autorisés sur une archive ouverte
Loading...

Dates et versions

inserm-00483164 , version 1 (12-05-2010)

Identifiants

Citer

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, 2009, 29 (2), pp.313-27. ⟨10.1523/JNEUROSCI.4093-08.2009⟩. ⟨inserm-00483164⟩

Collections

INSERM UNIV-AMU
139 Consultations
255 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More