The specific neuronal circuitry that provides the foundation for sleep-related electrical activities in the brain is composed of reciprocal loops between interconnected areas of thalamus and neocortex. There is emerging evidence that this circuitry can be compromised in humans with generalized absence epilepsy, with the result that normal oscillatory sleep rhythms are converted into pathological epileptic activities. Within the thalamic half of the thalamocortical loop synaptic mechanisms promote both normal and abnormal oscillatory patterns. It is our hypothesis that regulation of synaptic strength within the thalamus is a key factor in determining whether normal are transformed into those associated with absence epilepsy. As a first step in testing this hypothesis, presynaptic control mechanisms in the thalamus will be investigated. These presynaptic mechanisms are expected to reduce the efficacy of synaptic transmission and may play a key role in the prevention of the neuronal activity associated with absence seizures. Gamma-aminobutyric acid (GABA receptor agonists and antagonists are powerful regulators of experimental absence seizures. The presynaptic actions of these compounds will be examined in the two principle types of neurons in rat somatosensory thalamus, the inhibitory cells within nucleus Reticularis thalami (nRt) and the excitatory relay neurons in the ventrobasal complex (VB). A microscope fitted with differential interference optics will be used to obtain high quality whole-cell voltage-clamp recordings form neurons visualized in thalamic slices maintained in vitro. The results of these studies may lead to new approaches in the treatment of human generalized epilepsy.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS034774-04
Application #
2892030
Study Section
Neurology B Subcommittee 2 (NEUB)
Program Officer
Jacobs, Margaret
Project Start
1996-07-22
Project End
2001-05-31
Budget Start
1999-06-01
Budget End
2001-05-31
Support Year
4
Fiscal Year
1999
Total Cost
Indirect Cost
Name
Stanford University
Department
Neurology
Type
Schools of Medicine
DUNS #
800771545
City
Stanford
State
CA
Country
United States
Zip Code
94305
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