A new experimental genetic model of epilepsy: seizures and enhanced cognition

描述（申请人提供）：大脑的认知功能来源于广泛分布在大脑中的大量神经元的协调相互作用。虽然癫痫发作活动可以由过度兴奋的振荡网络驱动，但这些神经元放电的短暂同步似乎也与记忆巩固有关。因此，一个基本但尚未解决的问题是如何实现这种活动的精细协调。我们建议采用多学科方法研究癫痫发作和认知增强共存的新实验遗传模型。这项研究将有助于确定记忆形成和大脑节律背后的分子和细胞机制。此外，它可能会导致与记忆丧失相关的疾病如衰老、阿尔茨海默病和亨廷顿病的新治疗方法的发展，这些疾病都是PKR活性异常升高和gaba能突触传递改变的疾病。

DESCRIPTION (provided by applicant): The brain's cognitive functions derive from the coordinated interactions of large numbers of neurons that are widely distributed throughout the brain. Although seizure activity can be driven by hyperexcitable oscillatory networks, these transient synchronizations of neuronal discharges appear also to be involved in memory consolidation. Thus, a fundamental, yet unresolved, question is how this finely-tuned coordination of activity is achieved. We propose to use a multidisciplinary approach to study a new experimental genetic model of epilepsy in which seizures and enhanced cognition co-exist. This study will help to define the molecular and cellular mechanisms underlying both memory formation and brain rhythmicity. In addition, it could lead to the development of new treatments for conditions associated with memory loss such as aging, Alzheimer's disease, and Huntington's disease, all conditions where PKR activity is abnormally elevated and GABAergic synaptic transmission is altered. PUBLIC HEALTH RELEVANCE: Although some seizure disorders have been associated with extraordinary mental abilities, little is known about the causes or possible genetic mutations associated with this type of epilepsy. We propose to use a multidisciplinary approach to study a new experimental genetic model of epilepsy in which seizures and enhanced cognition co-exists. This study will help to define the common mechanisms underlying memory formation and seizure disorders and may lead to treatments for some major cognitive disorders such as aging, Huntington's disease, and Alzheimer's disease, all conditions where PKR activity and inhibitory synaptic transmission are altered.