EXCITATORY AMINO ACIDS AND FOCALLY EVOKED CONVULSIONS

参与边缘运动起始和传播的网络 从深部梨状叶皮质诱发的癫痫将使用 解剖学、药理学和神经生理学方法。 特别强调的是确定谷氨酸的作用 区域台风(AT)和主要目标中的传播 前梨状皮质内的致痫部位。这些目标包括 梨状后皮质(PPC)和虹膜周围皮质(PRC)， 嗅球(OB)和梨状预叶皮质浅层 (SLP)。需要检验的假设是：1)谷氨酸传递 (特别是通过非NMDA受体介导的)在PRC和PPC中是至关重要的 调节AT诱发的惊厥发作；2)抑制谷氨酸 在中国或PPC的双边传播将防止克隆 全身注射荷包牡丹碱引起的惊厥发作， 红藻氨酸和匹罗卡品；3)AT发出直接的兴奋性投射 对PPC和PRC，其中一些是谷氨酸能的；4)阻断谷氨酸 集中在PPC、PRC和OB的受体将阻止癫痫诱发 C-fos mRNA在这些区域的增加；5)OB是 含有投射到AT和靶的兴奋性氨基酸 来自AT的兴奋性投射；以及6)来自 AT可引起阵发性去极化移位和相关的猝发 SLP神经元和EAA传递介导了SLP的这些反应。 这些假说将使用选择性的焦点应用- 体内起作用的药物，并在适用的情况下，通过应用药物或 在体外维持脑片的电刺激。行为上的， 脑电和单个单位的记录将按顺序进行 监测癫痫发作活动和体内神经相互作用，而 将进行全细胞膜片钳和场电位记录 在脑片上。这些研究有望提供重要的 对NMDA和非NMDA传递在疾病发生中作用的认识 以及前脑癫痫的传播。通过体内和体外相结合 我们希望开始弥合两国之间现有差距的方法 EAA在局部环路中传播的药理学分析 边缘系统中的长距离回路的功能与 癫痫的发生。

The network involved in the initiation and propagation of limbic motor seizures evoked from the deep prepiriform cortex will be explored using anatomical, pharmacological and neurophysiological approaches. Particular emphasis will be on defining the role of glutamate transmission in the primary targets of area tempestas (AT) an epileptogenic site within the prepiriform cortex. These targets include the posterior piriform cortex (PPC) and perirhinal cortex (PRC), the olfactory bulb (OB), and the superficial layers of prepiriform cortex (SLP). The hypotheses to be tested are that 1) glutamate transmission (particularly mediated via non-NMDA receptors) in PRC and PPC is crucial for mediating AT-evoked convulsive seizures; 2) inhibition of glutamate transmission bilaterally in PRC or PPC will protect against clonic convulsive seizures evoked by systemically administered bicuculline, kainic acid and pilocarpine; 3) AT sends direct excitatory projections to PPC and PRC, some of which are glutamatergic; 4) blockade of glutamate receptors focally in PPC, PRC and OB will prevent the seizure-evoked increases in c-fos mRNA in these regions; 5) the OB is a source of excitatory amino acid containing projections to AT as well as a target of excitatory projections from AT; and 6) excitatory input to SLP from AT can induce paroxysmal depolarization shifts and related bursting in SLP neurons and that EAA transmission mediates these responses in SLP. These hypotheses will be treated using focal applications of selectively- acting drugs in vivo and, where applicable, by application of drugs or electrical stimulation in brain slices maintained in vitro. Behavioral, electroencephalographic, and single unit recordings will be made in order to monitor seizure activity and neural interactions in vivo, whereas whole-cell patch clamp and field potential recording will be conducted in brain slices. These studies are expected to provide important insights into the role of NMDA and non-NMDA transmission in the genesis and propagation of forebrain seizures. By combining in vivo and in vitro approaches we hope to begin to bridge the existing gap between the analysis of the pharmacology of EAA transmission in local circuits and that of long distance circuits in the limbic system as related to epileptogenesis.