ON THE PHARAMACOLOGY OF CONVULSANT DRUGS

该项目是一个持续的努力，探索神经机制 使感觉刺激在动物中引发癫痫发作的能力降低 模型包括用阈下剂量的惊厥药物治疗。 这些模型使探索神经元的反应，以可控的 能够引发癫痫发作并揭示信息的刺激 关于癫痫发作时大脑不同区域的神经元的作用 入会仪式 普遍缉获的突出组织方面， 通过癫痫发作活动的同时发作和抵消来证明 很难在体外研究， 考察 我们的研究结果表明，超过90%的脑干网状细胞， 形成（RF）神经元经历感觉反应性的显著变化 从无反应到治疗后有反应， 亚惊厥剂量的10种不同的惊厥药物，而神经元在 外侧膝状体、海马体和杏仁核仅显示微小变化。 十字韧带周围皮质的神经元比RF的神经元变化小，但 在网状神经元之间， 形成和十字韧带周围皮质神经元。 畸 广泛的惊厥诱导的RF神经元放电的夹带可以 通过后放电样效应促进癫痫发作的普遍化。 由于RF与其他大脑区域的广泛连接， 过度的神经元放电可能会扩散到整个大脑，引发 全身性癫痫 这样一个过程可能反映在打击 惊厥诱导的MRF和十字周围神经元放电的相关性。 我们还将研究间脑部位放电的变化， 从RF投射到十字韧带周围。 本研究将探讨的一般性， 在其他癫痫发作模型中增强感觉反应，包括 遗传性癫痫易感（GEP）大鼠和新皮质青霉素 专心点 诱发异常反应的可能突触机制 将通过观察GEP大鼠的神经元中是否存在 假定的兴奋性神经递质和抑制性神经递质的拮抗剂 神经递质在正常神经元中可产生后放电反应 在GEP神经元中显著可见。 脑实质的神经反应 将在GEP大鼠和惊厥药物中评价黑质，以确定 这一重要结构对癫痫发作机制的贡献， 模型 这些实验的完成将产生重大的新成果。 适用于理解感觉诱发癫痫发作的信息 在人类癫痫中观察到的刺激。

The project is a continuing effort to explore neuronal mechanisms subserving the ability of sensory stimuli to initiate seizure in animal models including treatment with subthreshold doses of convulsant drugs. These models enable exploration of neuronal responses to a controllable stimulus which is capable of initiating a seizure and reveals information about the role of neurons in different brain regions in seizure initiation. The prominent organizational aspects of generalized seizures, demonstrated by the simultaneous onset and offset of seizure activity throughout the brain which are difficult to study in vitro can be examined. Our findings indicate that over 90% of brainstem reticular formation (RF) neurons undergo striking changes in sensory responsiveness from being unresponsive to being quite responsive after treatment with subconvulsant doses of 10 different convulsant drugs, while neurons in lateral geniculate, hippocampus and amygdala show only minor changes. Neurons in pericruciate cortex show smaller changes than those in RF, but a striking convulsant-induced cross-correlation of firing between reticular formation and pericruciate cortical neurons is observed. The abnormally extensive convulsant-induced entrainment of RF neuronal firing could precipitate seizure generalization through an afterdischarge-like effect. Because of widespread connections of the RF to other brain regions, this excessive neuronal discharge may spread throughout the brain, triggering a generalized seizure. Such a process may be reflected in the striking convulsant-induced correlation of firing of MRF and pericruciate neurons. We will also examine the changes in firing of diencephalic sites which project from RF to pericruciate. This study will examine the generality of enhanced sensory responsiveness in additional models of seizure including the Genetically Epilepsy Prone (GEP) rat and the neocortical penicillin focus. The possible synaptic mechanisms subserving the abnormal response observed in neurons of the GEP rat will be examined by observing if putative excitatory neurotransmitters and antagonists of inhibitory neurotransmitters can produce the afterdischarge response in normal neurons seen prominently in GEP neurons. The neuronal responses in substantia nigra will be evaluated in GEP rat and with convulsant drugs to determine the contribution of this important structure to seizure mechanisms in these models. Completion of these experiments should yield significant new information applicable to understanding seizure initiation by sensory stimuli which is observed in human epilepsy.