A great amount of data have accumulated on the brainstem mechanisms of REM sleep. Emerging is an executive mechanism capable of recruiting all the components required for the confluence of many diverse processes constituting the REM sleep- state of arousal. Little understood, however, are the neural substrates subserving the temporal organization and modulation of time spent in REM sleep. One region in brain putatively exercising this function is the pontine reticular formation (PRF). Most compelling support for this role comes from the long lasting elevation in REM sleep amounts resulting from a single intracerebral microinjection of a cholinergic agonist into the medial PRF. The objective of this proposal is to elucidate the nature and mechanisms of ligand induced REM sleep increases. The PI has a new finding that adenosinergic mechanisms also operate in the pons in the control of REM sleep and will compare the action of adenosinergic and cholinergic ligands with respect to site specificity, dose, and action of antagonists. With the pontine micro-injection of different adenosine receptor ligands, the PI will determine the adenosine receptor subtype mediating effects on REM sleep. In addition, the PI hypothesizes that the long lasting effect of single, small-volume ligand injections is the result of long lasting intracellular changes in the pons mediated by signal transduction mechanisms. A behavioral pharmacological approach is proposed to determine if the local inhibition of the second messenger, cAMP, is sufficient to increase REM sleep. Preliminary data strongly indicate that cAMP has this role in the PRF. This project will begin to elucidate the mechanisms of the long-term control of REM sleep.
