NEUROTRANSMITTER SEIZURE MECHANISMS

这项提议将利用神经药理学技术来 评估癫痫发作所涉及的神经递质机制 遗传癫痫易感(GEP)大鼠。GEP大鼠极易患上 热、电击、惊厥和声音诱发的癫痫发作，并可能 作为某些形式的人类癫痫的有用遗传模型。上一首 研究表明，下丘和脑干网状结构。 队形在癫痫发作的产生中起着关键作用 自然发生的癫痫模型。神经化学证据和 药理学研究表明，神经递质异常 在这些癫痫动物的大脑中。我们的初步研究和 来自其他实验室的最新数据表明，药物的有效性降低 GABA的作用可能发生在这种癫痫模型中。这可能会导致 对听觉刺激的起效-抵消反应的发生率增加 我们在初步研究中观察到的GEP大鼠。正常的 去甲肾上腺素与GABA的相互作用也可能在这一过程中改变 患有癫痫的动物。拟议的研究将调查 这些可能的神经递质在GEP大鼠的IC神经元中是异常的。 局部(插管)置入对癫痫敏感性的影响 IC、网状结构和上丘是影响 这些神经递质也将被检查，以确定 这些结构在癫痫发作途径中的重要性。兴奋的感觉 氨基酸，谷氨酸和天冬氨酸，可能是兴奋性的。 IC中的神经递质。我们的初步研究表明， 这些药物的拮抗剂将显著降低癫痫发作的严重程度 GEP老鼠。因此，我们将研究其对IC神经元的影响。 这些兴奋性药物及其拮抗剂的反应。自.以来 已有报道称GEP大鼠的耳蜗出现异常，其反应 耳蜗核和上橄榄核内听神经元的形态 将对综合体进行调查，以确定是否发生反应异常 在这些投射到IC的核团中。这些研究应该会产生 关于神经递质机制的重要新信息 全身性癫痫的自然发生、终身遗传模型 可能对增进我们对其发病机制的了解有很大的价值 癫痫的发生。

This proposal will utilize neuropharmacological techniques in order to evaluate neurotransmitter mechanisms involved in seizures in the genetically epilepsy prone (GEP) rat. The GEP rat is highly susceptible to thermal, electroshock, convulsant and sound-induced seizures and may serve as a useful genetic model of certain forms of human epilepsy. Previous studies indicate that the inferior colliculus (IC) and brain-stem reticular formation play critical roles in the production of seizures in this naturally-occurring model of epilepsy. Neurochemical evidence and pharmacological studies indicate that neurotransmitter abnormalities occur in the brains of these epileptic animals. Our preliminary studies and recent data from other laboratories suggest that a reduced effectiveness of the action of GABA may occur in this epilepsy model. This may result in the increased incidence of onset-offset responses to auditory stimuli in the GEP rat that we have observed in preliminary studies. The normal interaction of norepinephrine with GABA may also be altered in this epileptic animal. The proposed study will investigate if the action of these putative neurotransmitters is abnormal in IC neurons in the GEP rat. The effects on seizure susceptibility of local (cannula) implantation into IC, reticular formation and superior colliculus of agents which affect these neurotransmitters will also be examined in order to determine the importance of these structures in the seizure pathway. The excitatory amino acids, glutamate and aspartate, are implicated as possible excitatory neurotransmitters in the IC. Our preliminary studies suggest that an antagonist of these agents will significantly reduce seizure severity in the GEP rat. Therefore, we will examine the effects on IC neuronal responses of these excitatory agents and their antagonists. Since abnormalities have been reported in the cochlea of GEP rats, the response patterns of auditory neurons in the cochlear nucleus and superior olivary complex will be investigated to determine if response abnormalities occur in these nuclei which project to IC. These studies should yield significant new information about neurotransmitter mechanisms in a naturally-occurring, life-long genetic model of generalized epilepsy which could be of great value in increasng our understanding of mechanisms of epileptogenesis.