EPILEPTOGENESIS IN THE AGED CNS

描述：(改编自应用程序)尽管具有流行病学 研究表明癫痫的发病率和流行率有所增加。 老年人精神障碍的潜在机制尚不清楚。目标是 这个项目的目的是研究生理机制， 有助于这种癫痫的发生。将使用年长的啮齿动物作为模型 因为几项研究表明癫痫发作也有类似的增加 在衰老过程中的易感性。申请者S初步学习 证实了这些发现并证明了增加的倾向 在神经细胞组织中也可以看到产生癫痫样活动 暴露于GABA-A受体拮抗剂后的隔离。这表明 在衰老过程中中枢神经系统可能发生变化，这可能是 增加了癫痫的易感性。齿状回将被检查，因为 据信，它在某些形式的癫痫和 已经描述了老年齿状回的解剖学变化 本质上会使人癫痫。他们的主要假设是 反复的兴奋和/或抑制是癫痫发作增加的基础 老年中枢神经系统的易感性。他们还将检查是否有改动 可能与非突触机制有关。 将使用几种电生理技术来测试这两项技术 老年大鼠的假说。将进行细胞内和细胞外录音 从颗粒细胞检测新的复发性兴奋性细胞的存在 并检测突触抑制的强度。胞外 记录将在低[Ca2+]o和高[K+]o介质中进行，其中 氨基酸受体拮抗剂测定是否有增加 老年大鼠齿状回发生非突触发作的易感性。 将进行解剖学研究以评估轴突的变化。 详述。 这些实验应该开始解决突触重组 和/或改变的非突触相互作用是癫痫发作增加的基础 老年人的易感性。其中一个长期目标是 了解老年人癫痫的发病机制，使患者 可以更有效地诊断和治疗。此外，突触 重组也可能影响其他海马区的过程，如学习 和记忆。因此，通过研究老年中枢神经系统内的突触重组 它们还可以提供对癫痫的基本机制的洞察和 在总人口中的学习和记忆。

DESCRIPTION: (Adapted from the application) Although epidemiological studies have demonstrated an increased incidence and prevalence of seizure disorders in the elderly, the underlying mechanisms are not known. The goal of this project is to investigate physiological mechanisms that could contribute to this epileptogenicity. Aged rodents will be used as the model system since several studies suggest a similar increase in seizure susceptibility during aging. The applicant s preliminary studies corroborate these findings and demonstrate that an increased propensity to generate epileptiform activity can also be seen in neuronal tissue in isolation following exposure to a GABA-A receptor antagonist. This suggests that alterations may occur in the CNS during aging that could underlie an increased seizure susceptibility. The dentate gyrus will be examined since it is believed to play a critical role in some forms of epilepsy and anatomical changes have been described in the aged dentate gyrus that could be epileptogenic in nature. Their primary hypothesis is that changes in recurrent excitation and/or inhibition underlie the increased seizure susceptibility in the aged CNS. They will also examine whether alterations in nonsynaptic mechanisms may be involved. Several electrophysiological techniques will be used to test these two hypotheses in aged rats. Intra- and extracellular recordings will be made from granule cells to test for the presence of new recurrent excitatory circuits and to examine the strength of synaptic inhibition. Extracellular recordings will be made in low [Ca2+]o and elevated [K+]o media containing amino acid receptor antagonists to determine if there is an increased susceptibility to generate nonsynaptic seizures in the dentate of aged rats. Anatomical studies will be performed to evaluate changes in axonal elaboration. These experiments should begin to address whether synaptic reorganization and/or altered nonsynaptic interactions underlie the increased seizure susceptibility in the elderly. One of the long-term objectives is to understand the mechanisms of epileptogenesis in the elderly so that patients can be diagnosed and treated more effectively. Additionally, synaptic reorganization may also affect other hippocampal processes such as learning and memory. Thus, by examining synaptic reorganization within the aged CNS they may also provide insight into the basic mechanisms of epilepsy and learning and memory within the overall population.