The long-term goal of this study is to understand the organization of cortical neuronal activity in sustained seizure events and in sensory processing. In this proposal, we will study a special form of population neuronal activity, namely, spiral waves. Spiral waves are a ubiquitous feature of excitable systems in nature, where they play a role in pattern formation and the organization of flow dynamics. Within biomedical science, spiral wave dynamics have been studied extensively in cardiac electrophysiology, and have greatly advanced our understanding of arrhythmogenic mechanisms. Surprisingly, however, only a few researchers have studied spiral dynamics in the brain. Following our recent discovery of spiral waves in rat neocortical slices, in this proposal, we will experimentally verify the existence of spiral waves in rodent neocortex in vivo during seizure-like events and during sensory evoked and spontaneous activity. Cortex in vivo has extensive long-range connections which are not present in brain slices. It is therefore necessary to experimentally examine the initiation and sustaining of spiral waves in intact cortex, given that strong long-range thalamocortical and corticocortical connections may disrupt the development of these spiral waves.
Three Specific Aims are proposed to study wave-to-wave interactions in rat sensory and motor cortices.
Aim 1 is devoted to improve voltage-sensitive dye imaging methods in order to identify phase singularities at the spiral center.
Aim 2 is to examine the incidence rate of spirals during seizure-like activity in various cortical areas.
Aim 3 is to investigate spiral dynamics during sensory-evoked activity and sleep-like waves. Studying spiral dynamics in the cortex will directly contribute to understanding of the initiation and sustaining of seizure activity. Spirals are known as a major contributor to arrhythmic activity in cardiac tissue, and extinguishing spirals in the heart has been a therapeutic strategy for preventing cardiac fibrillation. This project is highly relevant to the mission of the NINDS, and should contribute to the understanding of initiation and sustaining of epileptic activity in the cortex, which disturbs the life of about 1% of the US population.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS059034-04
Application #
8018046
Study Section
Special Emphasis Panel (ZRG1-IFCN-E (02))
Program Officer
Stewart, Randall R
Project Start
2008-02-15
Project End
2014-01-31
Budget Start
2011-02-01
Budget End
2014-01-31
Support Year
4
Fiscal Year
2011
Total Cost
$296,160
Indirect Cost
Name
Georgetown University
Department
Physiology
Type
Schools of Medicine
DUNS #
049515844
City
Washington
State
DC
Country
United States
Zip Code
20057
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