Abstract
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.
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Acknowledgments
We would like to thank Prof. Zhuan Zhou (Institute of Molecular Medicine, Peking University, China) for his technical assistance in the electrophysiological study. This work was supported by the National Natural Science Foundation of China (Nos. 81100975 and 81371430), Natural Science Foundation Project of CQ CSTC (No. 2011JJ0124), China Postdoctoral Science Foundation (No. 2012 T50850), Research Foundation of General Hospital of Chengdu Military Region (No. 424121H3), and Science Foundation of Health Office of Sichuan Province (No. 42412D16).
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Hai-Feng Shu and Yong-Qin Kuang contributed equally to this work.
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Supplementary Figure 1
Examples of hematoxylin and eosin (H&E)-stained sections from (a) P10 and (b) P30 DiI-FL rats. Note the infolded I-III cortical layers comprising the microgyrus (black arrow) and the microsulcus. (JPEG 14 kb)
Supplementary Figure 2
( a-c ) Immunohistochemical co-localization of CM-DiI positive cells with SYN. Arrows show double-positive cells for CM-DiI and SYN. Scale bars: 20 μm. ( d - e ) Representative electron micrographs showing the synaptic connection (red arrow) in CM-DiI positive cells. ( f ) Representative traces of spontaneous EPSCs recorded from a CM-DiI positive cell of P30 DiI-FL cortex. sEPSCs were abolished by application of CNQX and APV (bottom trace). (JPEG 19 kb)
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Shu, HF., Kuang, YQ., Liu, SY. et al. Endogenous Subventricular Zone Neural Progenitors Contribute to the Formation and Hyperexcitability of Experimental Model of Focal Microgyria. J Mol Neurosci 52, 586–597 (2014). https://doi.org/10.1007/s12031-013-0114-5
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DOI: https://doi.org/10.1007/s12031-013-0114-5