Endogenous subventricular zone neural progenitors contribute to the formation and hyperexcitability of experimental model of focal microgyria.
Microgyria is associated with epilepsy and due to developmental disruption of neuronal migration. However, the role of endogenous subventricular zone-derived neural progenitors (SDNPs) in formation and hyperexcitability has not been fully elucidated. Here, we establish a neonatal cortex freeze-lesion (FL) model, which was considered as a model for focal microgyria, and simultaneously label SDNPs by CM-DiI. Morphological investigation showed that SDNPs migrated into FL and differentiated into neuronal and glia cell types, suggesting the involvement of endogenous SDNPs in the formation of FL-induced microgyria. Patch-clamp recordings in CM-DiI positive (CM-DiI(+)) pyramidal neurons within FL indicated an increase in frequency of spontaneous action potentials, while the resting membrane potential did not differ from the controls. We also found that spontaneous excitatory postsynaptic currents (EPSCs) increased in frequency but not in amplitude compared with controls. The evoked EPSCs showed a significant increase of 10-90% in rise time and decay time in the CM-DiI(+) neurons. Moreover, paired-pulse facilitation was dramatically larger in CM-DiI(+) pyramidal neurons. Western blotting data showed that AMPA and NMDA receptors were increased to some extent in the FL cortex compared with controls, and the NMDA/AMPA ratio of eEPSCs at CM-DiI(+) pyramidal neurons was significantly increased. Taken together, our findings provide novel evidence for the contribution of endogenous SDNPs in the formation and epileptogenicity of FL-induced focal microgyria.
Department of Neurosurgery, General Hospital of the People's Liberation Army Chengdu Military Region, Sichuan, 610000, China.
Hai-Feng
HF
Shu
Yong-Qin
YQ
Kuang
Shi-Yong
SY
Liu
Si-Xun
SX
Yu
Chun-Qing
CQ
Zhang
Da-Hai
DH
Zheng
Jian-Wen
JW
Gu
Hui
H
Yang
D000200:Action Potentials / Q000502:physiology; D000818:Animals; D000831:Animals, Newborn; D002232:Carbocyanines / Q000633:toxicity; D002465:Cell Movement / Q000502:physiology; D004195:Disease Models, Animal; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology; D007276:Injections, Intraventricular; D054220:Malformations of Cortical Development / Q000139:chemically induced / Q000473:pathology* / Q000503:physiopathology*; D058953:Neural Stem Cells / Q000166:cytology* / Q000502:physiology*; D009924:Organ Culture Techniques; D018408:Patch-Clamp Techniques; D017966:Pyramidal Cells / Q000473:pathology / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017470:Receptors, Glutamate / Q000502:physiology; D055153:Stem Cell Niche / Q000502:physiology*
C434385:3,3'-dioactadecyl-5,5'-di(4-sulfophenyl)oxacarbocyanine; D002232:Carbocyanines; D017470:Receptors, Glutamate