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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
1R01NS076708-01A1
Application #
8304789
Study Section
Clinical Neuroplasticity and Neurotransmitters Study Section (CNNT)
Program Officer
Whittemore, Vicky R
Project Start
2012-03-15
Project End
2017-02-28
Budget Start
2012-03-15
Budget End
2013-02-28
Support Year
1
Fiscal Year
2012
Total Cost
$342,344
Indirect Cost
$123,594
Name
Baylor College of Medicine
Department
Neurosciences
Type
Schools of Medicine
DUNS #
051113330
City
Houston
State
TX
Country
United States
Zip Code
77030
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Costa-Mattioli, Mauro; Monteggia, Lisa M (2013) mTOR complexes in neurodevelopmental and neuropsychiatric disorders. Nat Neurosci 16:1537-43