Brain Research, 98 (1975) 501-515 501 © Elsevier ScientificPublishing Company, Amsterdam - Printed in The Netherlands SLEEP CYCLE CONTROL AND CHOLINERGIC MECHANISMS: DIFFER- ENTIAL EFFECTS OF CARBACHOL INJECTIONS AT PONTINE BRAIN STEM SITES THOMAS T. AMATRUDA, III, DEBORAH A. BLACK, THOMAS M. McKENNA, ROBERT W. McCARLEY ANDJ. ALLAN HOBSON* Laboratory of Neurophysiology, Department of Psychiatry, Harvard Medical School, Boston, Mass 02115 (U.S.A.) (Accepted May 7th, 1975) SUMMARY Muscular atonia and cortical desynchronization, two signs of desynchronized sleep, can be enhanced or suppressed by direct injection of carbachol into the pontine brain stem of cats. The positive effects are graded, being maximal in the giganto- cellular tegmental field and less marked in adjacent nuclei. These positive effects are dose-dependent. Suppressive effects of carbachol are maximal in the region of the locus coeruleus and are dose-dependent but do not exceed those of the vehicle alone. The results support the hypothesis that cholinergic mechanisms of the pontine teg- mentum are involved in desynchronized sleep generation. INTRODUCTION Lesion 15, stimulation 6, and microelectrode recording la experiments indicate that the giant cells of the gigantocellular tegmental field (FTG) play an executive role in generating some of the phasic and tonic events of desynchronized sleep. While locus coeruleus (LC) lesions also disrupt desynchronized sleep 26, recordings from single cells in its caudal pole have shown a state-related discharge pattern reciprocal to that of FTG cells 14, suggesting that the arrest of LC cell discharge at desynchronized sleep onset might disinhibit the FTG. Thus the role of the LC in desynchronized sleep generation might also be critical but permissive rather than executive. The physiological observations cited above suggest a physiological model for the periodic occurrence of desynchronized sleep that is based upon reciprocal inter- * Author to whom reprint requests should be addressed.