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

描述(申请人提供)：大脑的认知功能来自广泛分布在大脑各处的大量神经元的协调相互作用。虽然癫痫发作活动可以由超兴奋的振荡网络驱动，但这些神经元放电的瞬时同步似乎也参与了记忆巩固。因此，一个根本但尚未解决的问题是，如何实现这种微调的活动协调。我们建议使用多学科方法来研究癫痫发作和认知增强共存的新的实验性遗传模型。这项研究将有助于确定记忆形成和大脑节律性的分子和细胞机制。此外，它还可能导致开发新的治疗方法，用于治疗与记忆丧失相关的疾病，如衰老、阿尔茨海默病和亨廷顿病，这些疾病都会导致PKR活性异常升高和GABA能突触传递改变。

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.