Characterization of neuronal migration disorders in neocortical structures: extracellular <i>in vitro</i> recordings

European Journal of Neuroscience - Tập 10 Số 10 - Trang 3085-3094 - 1998
Heiko J. Luhmann1, Kristin Raabe1, M Qü2, Karl Zilles2
1Institute of Neurophysiology, and
2C. & O. Vogt Institute of Brain Research, University of Düsseldorf, PO Box 101007, D-40001 Düsseldorf, Germany

Tóm tắt

AbstractThe majority of patients showing neuronal migration disorders in cortical structures suffer from pharmaco‐resistant epilepsy. In order to study the molecular and cellular mechanisms underlying this pronounced hyperexcitability, we used an animal model of focal cortical dysplasia demonstrating structural malformations which resemble the human pathology of microgyria. Neocortical slices prepared from adult rats, which at the day of birth received a cortical freeze lesion, were analysed in vitro with an array of eight extracellular recording electrodes to investigate the pattern and pharmacology of propagating epileptiform activity in microgyric cortex. In cortical slices exhibiting neuronal migration disorders, orthodromic synaptic stimulation elicited late recurrent activity and early epileptiform responses that spread with 0.06 m/s over ≥ 3.5 mm across the cortex. Application of a N‐methyl‐d‐aspartate (NMDA) antagonist blocked the late recurrent activity, but not the propagation of the early epileptiform responses. The latter were blocked by an (±)‐α‐amino‐3‐hydroxy‐5‐methylisoxazole‐4‐propionic acid (AMPA) antagonist, indicating that the spread of this activity was predominantly mediated by activation of AMPA receptors. A very similar response pattern could be observed in neocortical slices obtained from untreated age‐matched control rats, when the slice was partially disinhibited by bath‐application of 5 μm bicuculline methiodide. Stimulus‐evoked epileptiform signals recorded in disinhibited slices propagated with 0.08 m/s across the cortex and showed the same sensitivity to ionotropic glutamate antagonists as in dysplastic cortex. Our results indicate that widespread structural and/or functional modifications of the AMPA receptor and possibly also of the γ‐amino‐butyric acid type A receptor contribute to the pronounced hyperexcitability in dysplastic cortex.

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Thông tin xuất bản

European Journal of Neuroscience

Tập 10 Số 10

3085-3094

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