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.
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.
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