Dopamine's modulation of wake/sleep state remains under-recognized and poorly defined. Impaired arousal and fragmented sleep characterize dopamine deficient conditions such as Parkinson's disease (PD); and the degree of dopamine released synoptically by blockade of the dopamine transporter (DAT) best predicts the alerting potency of drugs. In humans, non-human primate, and rodent models of PD we have observed that nigrostriatal dopamine loss disrupts thalamocortical aroused states such as wakefulness and rapid-eye-movement (REM) sleep. Our recent demonstration that the nigrostriatal system collateralizes extensively to innervate the thalamus identifies the thalamus as a novel substrate that may underlie dopamine's modulation of normal and pathological wake/sleep. The thalamus, however, is generally regarded to lack dopaminergic input and only one study has investigated dopamine's effects upon thalamic activity in vivo. Therefore, we propose in Aim #1 to map the dopaminergic innervation of the non-human primate and human thalamus.
Aim #2 proposes to define the origin, topography, and extent of collateralization of this innervation in rats and non human primates.
Aim #3 employs microdialysis with simultaneous determination of behavioral state, and extracellular unit recording in non human primates, to investigate the relevance of this innervation to wake/sleep state.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Predoctoral Individual National Research Service Award (F31)
Project #
5F31MH064312-03
Application #
6656345
Study Section
Special Emphasis Panel (ZRG1-IFCN-3 (01))
Program Officer
Desmond, Nancy L
Project Start
2002-09-01
Project End
Budget Start
2003-09-01
Budget End
2004-08-31
Support Year
3
Fiscal Year
2003
Total Cost
$24,803
Indirect Cost
Name
Emory University
Department
Neurology
Type
Schools of Medicine
DUNS #
066469933
City
Atlanta
State
GA
Country
United States
Zip Code
30322
Daley, Joseph T; Turner, Robert S; Freeman, Amanda et al. (2006) Prolonged assessment of sleep and daytime sleepiness in unrestrained Macaca mulatta. Sleep 29:221-31