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.
| 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 |
