Normotopic cortex is the major contributor to epilepsy in experimental double cortex
Ludovic Franck Petit1, Marion Jalabert, Emmanuelle Buhler
1Institut de Neurobiologie de la Méditerranée/Institut National de la Santé et de la Recherche Médicale U901, Marseille, France; Aix-Marseille University, Marseille, France.
Annals of Neurology
|July 31, 2014
Summary
Subcortical band heterotopia (SBH) is linked to epilepsy. This study found the overlying cortex, not the heterotopia band, generates seizures in SBH rats, suggesting a key role for the cortex in epilepsy.
Area of Science:
- Neuroscience
- Developmental Neuroscience
- Epileptology
Background:
- Subcortical band heterotopia (SBH) is a neuronal migration disorder causing intractable epilepsy.
- The precise origin of epileptiform activity in SBH remains unclear, with contributions from both the heterotopic band and overlying cortex.
- Identifying the critical epileptogenic zone is crucial for understanding and treating SBH-associated epilepsy.
Purpose of the Study:
- To investigate the origin of epileptiform activity in a genetic rat model of subcortical band heterotopia (SBH).
- To determine whether the heterotopic band or the overlying cortex is the primary source of seizures in SBH.
- To elucidate the role of the normotopic cortex and heterotopic band in the generation and propagation of epileptic discharges.
Main Methods:
- Subcortical band heterotopia (SBH) was induced in rats by knocking down the Dcx gene (Dcx-KD rats).
- Extracellular recordings using microelectrode arrays analyzed bicuculline-induced interictal-like activity in neocortical slices.
- Electrocorticography assessed seizure susceptibility in response to pentylenetetrazole in vivo.
Main Results:
- The heterotopic band in SBH rats did not generate primary interictal-like activity in vitro and was not essential for induced seizures in vivo.
- Interictal-like discharges predominantly originated in the overlying cortex and secondarily propagated to the heterotopic band.
- In vivo suppression of neuronal excitability within the SBH band did not reduce seizure propensity in Dcx-KD rats.
Conclusions:
- The normotopic cortex plays a critical role in generating interictal epileptiform activity and seizures in subcortical band heterotopia.
- These findings shift the focus from the heterotopic band to the overlying cortex as the primary epileptogenic zone in SBH.
- Understanding the cortical contribution is vital for developing targeted therapies for SBH-related epilepsy.
