The mechanisms by which a diverse group of pharmacological agents produce anesthesia remain uncertain. A potentially important region within the central nervous system (CNS) for contributing to the anesthetized state is the thalamus; it is a critical relay site for sensory information, and two specific nuclei, the ventrobasal nucleus and the reticular nucleus, are considered to be essential structures in the generation of consciousness and sleep. Since anesthetics depress consciousness and induce """"""""sleep,"""""""" it is important to understand how anesthetics alter synaptic transmission and cell physiology in these two regions. Inhibitory synaptic transmission helps regulate thalamic function, and the GABA-A receptor is the primary receptor for mediating fast inhibitory synaptic transmission within the CNS. The focus of this proposal is to explore how two different anesthetic agents, the volatile anesthetic - isoflurane, and the intravenous anesthetic - propofol, modulate inhibitory synaptic transmission and neuronal activity in the ventrobasal nucleus and reticular nucleus.
Aim 1 - What are the effects of propofol on synaptic transmission and membrane excitability in the thalamus? The hypothesis to be tested is that propofol will potentiate synaptic inhibition and depress neuronal activity to a greater extent in VB neurons than in RTN neurons.
Aim 2 - What are the effects of isoflurane on synaptic transmission and membrane excitability in the thalamus? The hypothesis to be tested is that isoflurane will potentiate synaptic inhibition and depress neuronal activity to a greater extent in VB neurons than in RTN neurons.
Aim 3 - How do propofol and isoflurane affect the ability of the RTN to regulate action potential firing in the VB? The hypothesis to be tested is that both agents will facilitate RTN-induced inhibition of action potential firing in VB neurons. By better understanding how anesthetic agents interact with specific subunits of the GABA-A receptor in different regions of the brain, it may be possible to design more selective, and therefore safer, anesthetics.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM066840-05
Application #
7324133
Study Section
Surgery, Anesthesiology and Trauma Study Section (SAT)
Program Officer
Cole, Alison E
Project Start
2004-01-01
Project End
2008-11-30
Budget Start
2007-12-01
Budget End
2008-11-30
Support Year
5
Fiscal Year
2008
Total Cost
$262,039
Indirect Cost
Name
Weill Medical College of Cornell University
Department
Anesthesiology
Type
Schools of Medicine
DUNS #
060217502
City
New York
State
NY
Country
United States
Zip Code
10065
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