BEHAVIORAL STATE CONTROL THROUGH DIFFERENTIAL SEROTONERGIC INHIBITIONIN THE MESOPONTINE CHOLINERGIC NUCLEI - A SIMULTANEOUS UNIT RECORDINGAND MICRODIALYSIS STUDY

Cholinergic neurons of the mesopontine nuclei are strongly implicated in behavioral state regulation. One population of neurons in the choli nergic zone of the laterodorsal tegmentum and the pedunculopontine nuc lei, referred to as rapid eye movement (REM)-on neurons, shows prefere ntial discharge activity during REM sleep, and extensive data indicate a key role in production of this state. Another neuronal group presen t in the same cholinergic zone of the laterodorsal tegmentum and the p edunculopontine nuclei, referred to as Wake/REM-on neurons, shows pref erential discharge activity during both wakefulness and REM sleep and is implicated in the production of electroencephalographic activation in both of these states. To test the hypothesis of differential seroto nergic inhibition as an explanation of the different state-related dis charge activity, we developed a novel methodology that enabled, in fre ely behaving animals, simultaneous unit recording and local perfusion of neuropharmacological agents using a microdialysis probe adjacent to the recording electrodes. Discharge activity of REM-on neurons was al most completely suppressed by local microdialysis perfusion of the sel ective 5-HT1A agonist 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DP AT), although this agonist had minimal or no effect on the Wake/REM-on neurons. We conclude that selective serotonergic inhibition is a basi s of differential state regulation in the mesopontine cholinergic nucl ei, and that the novel methodology combining neurophysiological and ne uropharmacological information from the freely behaving animal shows g reat promise for further insight into the neural basis of behavioral c ontrol.