The brainstem reticular formation comprises one of the distributed mechanisms underlying the control of rapid eye movement (REM) sleep. A circumscribed region in the caudal, nucleus pontis oralis (PnOc) of the rat is distinguished as a site in the reticular formation in which small intracerebral injections of a variety of neurotransmitter-related agents induce long-lasting elevations in REM sleep. These and other data support a critical role for this region of brain in the long-term control of the expression of REM sleep. The broad objective of this proposal is to elucidate the neural mechanisms in the PnOc subserving REM sleep.
The specific aims are a continuation of our ongoing work investigating the actions of adenosine, acetylcholine, gamma-aminobutyric acid (GABA) and the intracellular second messenger, cyclic adenosine 3',5'-monophosphate (cAMP). Methods of behavioral pharmacology will be used to determine the muscarinic receptor subtypes and the nature of the possible interaction between identified adenosine receptor subtypes mediating agonist-induction of REM sleep. Inhibition of cAMP formation will be confirmed as a mechanism sufficient to result in long-lasting elevations in REM sleep, and mediation through cAMP-dependent protein kinase A will be tested. The neurotransmitter GABA will be tested as a mechanism of shorter lasting control over REM sleep. Utilizing in vivo microdialysis of the PnOc, mechanisms of GABA release will be tested for its role in natural and drug induced control of REM sleep. This project will continue the uncovering of brainstem mechanisms involved in the long-term control of REM sleep. Data forthcoming from these studies will yield a better understanding of the mechanisms mediating sleep-state control at the cellular level. Information concerning these control mechanisms are essential to understanding the physiological processes manifested during both normal and pathological sleep/wake states.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
2R01MH057434-04A2
Application #
6620304
Study Section
Special Emphasis Panel (ZRG1-IFCN-3 (01))
Program Officer
Nichols, Paul L
Project Start
1998-12-01
Project End
2008-03-31
Budget Start
2003-04-01
Budget End
2004-03-31
Support Year
4
Fiscal Year
2003
Total Cost
$315,000
Indirect Cost
Name
University of Texas Sw Medical Center Dallas
Department
Psychiatry
Type
Schools of Medicine
DUNS #
800771545
City
Dallas
State
TX
Country
United States
Zip Code
75390