OPTICAL IMAGING OF SEIZURE PROPAGATION

尽管我们关于细胞和细胞的知识取得了许多进步 癫痫的分子机制，但进展较少 这些机制涉及癫痫发作活动和周围的扩散 抑制力。更详细地了解癫痫的传播和 癫痫的环绕抑制、药物和外科治疗 可以设计得更好。利用光学成像和微电极 大鼠、灵长类动物和人类癫痫模型的记录，P.I.有 更好地了解这些机制的独特机会 与人类新皮质癫痫有关。 CIDA的这项建议侧重于癫痫发作所涉及的新皮质机制 传播和环绕抑制在不同的 癫痫模型。三种致痫刺激将应用于In 大鼠和人的体外新皮质切片--包括低剂量或局灶性切片 荷包牡丹碱(GABA-A拮抗剂)的应用； 细胞外钾浓度；或笼养的光刺激 谷氨酸。正常人新皮质区域间的相互作用 将研究的条件和新皮质层，容易 将对扣押活动的启动进行描述。那么， 用于癫痫传播的首选路径和区域特定路径将 通过微电极记录(细胞内/细胞外)和 光学成像。区域中“抑制”光信号的性质 癫痫灶周围将通过相互关联来确定 细胞内微电极记录与光学成像。光学 成像和微电极记录也将用于检查 灵长类癫痫的传播途径和周围抑制 视觉皮质和完好无损的人类新皮质。在灵长类中，功能性的 将获得视觉皮质的地图，并将诱发癫痫发作活动 局部应用或低剂量荷包牡丹碱灌流； 高钾浓度溶液的灌流；或 微刺激。在人类身上，作为常规测定的一部分 用于语言映射的癫痫阈值，微刺激将用于 引起局灶性癫痫样活动。在这些完整的准备工作中， 癫痫发作活动在更大的皮质表面积上的传播 周围抑制的程度将通过光学成像进行监测。

Despite many advances in our knowledge regarding the cellular and molecular mechanisms underlying epilepsy, less progress has been made in those mechanisms involved in the spread of seizure activity and surround inhibition. With a more detailed knowledge of seizure propagation and surround inhibition, pharmaceutical and surgical treatments for epilepsy could be better devised. By using optical imaging and microelectrode recordings of rat, primate, and human models of epilepsy, the P.I. has the unique opportunity to gain a better understanding of those mechanisms involved in human neocortical epilepsy. This CIDA proposal focuses on neocortical mechanisms involved in seizure propagation and surround inhibition that are common between different models of epilepsy. Three epileptogenic stimuli will be applied to in vitro rat and human neocortical slices- including low-dose or focal application of bicuculline (GABA-A antagonist); increases in the extracellular potassium concentration; or photostimulation with caged glutamate. The interaction between neocortical regions in normal conditions will be studied and the neocortical layers that are prone to the initiation of seizure activity will be characterized. Then, the preferred and regional-specific pathways used for seizure propagation will be studied with microelectrode recordings (intra-/extra-cellular) and optical imaging. The nature of "inhibitory" optical signals in areas surrounding the epileptic focus will be determined by correlating intracellular microelectrode recordings with optical imaging. Optical imaging and microelectrode recordings will also be used to examine pathways of seizure propagation and surround inhibition in the primate visual cortex and the intact human neocortex. In the primate, functional maps of visual cortex will be obtained and seizure activity will be evoked with focal applications or low-dose superfusion of bicuculline; superfusion of solutions with a high potassium concentrations; or microstimulation. In humans, as part of the routine determination of seizure thresholds for language mapping, microstimulation will be used to evoke focal epileptiform activity. In these intact preparations, the propagation of seizure activity over a larger surface area of cortex and the extent of surround inhibition will be monitored by optical imaging.