Excitation of the Brainstem Pedunculopontine Tegmentum Cholinergic Cells
Induces Wakefulness and REM Sleep.
Subimal Datta and Donald F. Siwek.
Department of Psychiatry, Harvard Medical School, Boston, Massachusetts
02115, Center for Behavioral Development and Mental Retardation, Department of
Psychiatry, Boston University School of Medicine, Massachusetts 02118, and
Department of Anatomy and Neurobiology, Boston University School of Medicine,
Boston, Massachusetts 02118, ENRM VAMC, Bedford, MA 01730.
APStracts 4:0063N, 1997.
ABSTRACT
Considerable evidence suggests that brainstem pedunculopontine tegmentum (PPT)
cholinergic cells are critically involved in the normal regulation of
wakefulness and rapid eye movement (REM) sleep. However, much of this evidence
comes from indirect studies. Thus, while involvement of PPT cholinergic
neurons has been suggested by numerous investigations, the excitation of PPT
cholinergic neurons causal to the behavioral state of wakefulness and REM
sleep has never been directly demonstrated. The present study examined the
effects of three different levels of activation of PPT cholinergic cells in
wakefulness and sleep behavior. The effects of glutamate on the activity of
PPT cholinergic cells was studied by microinjecting one of the three different
doses of L-glutamate (0.3 mg, 1.0 mg, and 3.0 mg) or saline (vehicle control)
into the PPT cholinergic cell compartment, while quantifying the effects on
wakefulness and sleep in free moving chronically instrumented cats. All
microinjections were made during wakefulness and were followed by 4 hours of
recording. Polygraphic records were scored for wakefulness, slow-wave sleep
(S)-1, S-2, S with PGO (SP), and REM sleep. Dependent variables quantified
following each microinjection included the percentage of recording time spent
in each state, the latency to onset of REM sleep, the number of episodes per
hour for REM sleep, and the duration of each REM sleep episode. A total of 48
microinjections were made into 12 PPT sites in six cats. Microinjection of 0.3
mg and 1.0 mg doses of L-glutamate into the cholinergic cell compartment of
the PPT increased the total amount of REM sleep in a dose dependent manner.
Both doses of L-glutamate increased REM sleep at the expense of S but not
wakefulness. Microinjection of 3.0 mg dose of L-glutamate kept animals awake
for 2 to 3 hours by eliminating S and REM sleep. The results show that the
microinjection of the excitatory amino acid, L-glutamate, into the PPT
cholinergic cell compartments can increase wakefulness and/or REM sleep
depending on the L-glutamate dosage. These findings unambiguously confirm the
hypothesis that the excitation of the PPT cholinergic cells are causal to the
generation of wakefulness and REM sleep.
Received 15 October 1996; accepted in final form 3 February 1997.
APS Manuscript Number J817-6.
Article publication pending J. Neurophysiol.
ISSN 1080-4757 Copyright 1997 The American Physiological Society.
Published in APStracts on 20 February 1997