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The Journal of Neuroscience, July 15, 1998, 18(14):5490-5497
Behavioral State Control through Differential Serotonergic
Inhibition in the Mesopontine Cholinergic Nuclei: A Simultaneous Unit
Recording and Microdialysis Study
Mahesh M.
Thakkar,
Robert E.
Strecker, and
Robert W.
McCarley
Department of Psychiatry, Harvard Medical School, Brockton Veterans
Administration Medical Center, Brockton, Massachusetts 02401
Cholinergic neurons of the mesopontine nuclei are strongly
implicated in behavioral state regulation. One population of neurons in
the cholinergic zone of the laterodorsal tegmentum and the pedunculopontine nuclei, referred to as rapid eye movement (REM)-on neurons, shows preferential discharge activity during REM sleep, and
extensive data indicate a key role in production of this state. Another
neuronal group present in the same cholinergic zone of the laterodorsal
tegmentum and the pedunculopontine nuclei, referred to as Wake/REM-on
neurons, shows preferential 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 serotonergic inhibition as an explanation of
the different state-related discharge activity, we developed a novel
methodology that enabled, in freely 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 almost completely suppressed by local
microdialysis perfusion of the selective 5-HT1A agonist 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT),
although this agonist had minimal or no effect on the Wake/REM-on
neurons. We conclude that selective serotonergic inhibition is a basis of differential state regulation in the mesopontine cholinergic nuclei,
and that the novel methodology combining neurophysiological and
neuropharmacological information from the freely behaving animal shows
great promise for further insight into the neural basis of behavioral
control.
Key words:
REM sleep; serotonin; laterodorsal tegmental nucleus; pedunculopontine tegmental nucleus; mesopontine cholinergic neurons; microdialysis; single-unit recording
Copyright © 1998 Society for Neuroscience 0270-6474/98/18145490-08$05.00/0
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