Glutamate biosensor imaging reveals dysregulation of glutamatergic pathways in a model of developmental cortical malformation
Glutamate biosensor imaging reveals dysregulation of glutamatergic pathways in a model of developmental cortical malformation
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DOI：
10.1016/j.nbd.2012.09.001
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发表时间：
2013-01-01
影响因子：
6.1
通讯作者：
Huguenard, J. R.
中科院分区：
文献类型：
--
作者：
Dulla, C. G.;Tani, H.;Huguenard, J. R.
皮质畸形可引起难治性癫痫，但其潜在的致痫机制尚不清楚。我们使用高速谷氨酸生物传感器成像来询问新生儿冷冻损伤（FL）诱导的皮质畸形中谷氨酸能信号是如何改变的。在2 ~ 8周龄大鼠的非病变新皮层切片中，诱发的谷氨酸信号在中-外侧轴上是对称的，并且是单调的，与简单的、简短的（约50 ms）局部场电位（LFPs）相关。与此相反，在FL皮质谷氨酸信号延长，幅度增加，多相，这意味着延长LFP。使用谷氨酸生物传感器成像，我们发现，谷氨酸信号传播整个大面积的FL皮质，是不对称的（偏向病变）。层流分析表明，在该地区的最大谷氨酸释放向浅层FL皮质的转变。去除外源性谷氨酸的能力在FL本身内增加，但在紧邻区域内减少。星形胶质细胞密度也有相应的改变，病变内增加，病变周围深层皮质层减少。这些研究结果表明，网络连接和谷氨酸代谢的改变，在这个皮质畸形模型，并表明星形胶质细胞的区域能力，以消除释放谷氨酸可能是负相关的局部兴奋性。(C)2012 Elsevier Inc. All rights reserved.
Cortical malformations can cause intractable epilepsy, but the underlying epileptogenic mechanisms are poorly understood. We used high-speed glutamate biosensor imaging to ask how glutamatergic signaling is altered in cortical malformations induced by neonatal freeze-lesions (FL). In non-lesion neocortical slices from 2 to 8 week old rats, evoked glutamate signals were symmetrical in the medio-lateral axis and monotonic, correlating with simple, brief (approximate to 50 ms) local field potentials (LFPs). By contrast, in FL cortex glutamate signals were prolonged, increased in amplitude, and polyphasic, which paralleled a prolongation of the LFP. Using glutamate biosensor imaging, we found that glutamate signals propagated throughout large areas of FL cortex and were asymmetric (skewed toward the lesion). Laminar analysis demonstrated a shift in the region of maximal glutamate release toward superficial layers in FL cortex. The ability to remove exogenous glutamate was increased within the FL itself but was decreased in immediately adjacent regions. There were corresponding alterations in astrocyte density, with an increase within the lesion and a decrease in deep cortical layers surrounding the lesion. These findings demonstrate both network connectivity and glutamate metabolism are altered in this cortical malformation model and suggests that the regional ability of astrocytes to remove released glutamate may be inversely related to local excitability. (C) 2012 Elsevier Inc. All rights reserved.