OPTICAL IMAGING OF SEIZURE PROPAGATION

尽管我们在细胞和神经系统方面的知识有了很大的进步， 癫痫的分子机制，但在 这些机制参与了癫痫活动的传播， 抑制作用有了更详细的癫痫传播知识， 癫痫周围抑制、药物和手术治疗 可以更好地设计。利用光学成像和微电极技术 记录大鼠，灵长类动物和人类癫痫模型，P.I.具有 更好地了解这些机制的独特机会 与人类新皮层癫痫有关 加拿大国际开发署的这一建议侧重于癫痫发作的新皮层机制 传播和周围的抑制，这是常见的不同 癫痫模型三种致癫痫刺激将被施加到 体外大鼠和人新皮质切片-包括低剂量或局灶性 应用荷包牡丹碱（GABA-A拮抗剂）; 细胞外钾浓度;或光刺激与笼 谷氨酸盐。正常人大脑皮层区域间的相互作用 条件将被研究，新皮质层，容易发生 将表征癫痫发作活动的开始。然后 用于癫痫传播的优选和区域特异性途径将 使用微电极记录（细胞内/细胞外）进行研究， 光学成像区域中"抑制性"光信号的性质 将通过将癫痫病灶周围的 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 灵长类癫痫发作传播和周围抑制的途径 视觉皮层和完整的人类新皮层。在灵长类动物中， 将获得视觉皮层的地图， 局部应用或低剂量荷包牡丹碱灌注; 灌注高钾浓度溶液;或 微刺激在人类中，作为常规测定的一部分， 语言映射的癫痫发作阈值，微刺激将用于 引起局灶性癫痫样活动。在这些完整的制剂中， 癫痫发作活动在皮层更大表面积上的传播， 通过光学成像监测周围抑制的程度。

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.