Understanding absence epilepsy will require understanding thalamic oscillations. The long term goal of this research is to use computer models to integrate known details of intrinsic neuronal properties and synaptic inputs to explain the genesis of the physiological and pathological slow rhythms of the thalamus. Intrinsic cell dynamics and synaptic connectivity interact in complex ways. Models of individual brain areas can provide a framework for integrating new physiological and pharmacological observations. A complement to animal models of epilepsy, computer models have the flexibility to extensively explore complex neuronal interactions that may suggest new pharmacological approaches. Slow oscillations in the thalamus, in both the 3 Hz range of absence epilepsy and slow-wave sleep in the 10 Hz range of sleep spindles, appear to involve low-threshold calcium spikes due to the T-type calcium channel (T channel). Ethosuximide, an anticonvulsant used for absence epilepsy, alters the kinetics of this channel. Computer modeling will be used 1) to determine the effects of passive properties and dendritic ion channels on the integrative properties of the neurons, 2) to relate neuronal firing patterns to the density and kinetics of ion channels, 3) to evaluate how physiological and pharmacological modulation of ion channels might alter the intrinsic oscillations of thalamocortical neurons, 4) to explore how repetitive intracellular stimulation or repetitive cortical synaptic input would affect oscillatory patterns, 5) to evaluate the contribution of intrinsic versus network properties in synchronizing slow oscillations in networks of simplified model neurons.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
First Independent Research Support & Transition (FIRST) Awards (R29)
Project #
5R29NS032187-03
Application #
2270191
Study Section
Cognitive Functional Neuroscience Review Committee (CFN)
Project Start
1993-05-14
Project End
1998-04-30
Budget Start
1995-05-01
Budget End
1996-04-30
Support Year
3
Fiscal Year
1995
Total Cost
Indirect Cost
Name
University of Wisconsin Madison
Department
Neurology
Type
Schools of Medicine
DUNS #
161202122
City
Madison
State
WI
Country
United States
Zip Code
53715