Interactions between cholinergic and GABAergic neurotransmitters in and around the locus coeruleus for the induction and maintenance of rapid eye movement sleep in rats

The noradrenergic "REM-off"neurons in the locus coeruleus cease firing, whe reas some cholinegic and non-cholinereic "REM-on" neurons increase firing d uring rapid eye movement sleep. A reciprocal interaction between these neur ons was proposed. However, acetylcholine did not inhibit neurons in the loc us coeruleus. Nevertheless, since GABA Levels increase during rapid eye mov ement sleep and picrotoxin injections into the locus coeruleus reduced rapi d eye movement sleep, it was hypothesized that GABA in the locus coeruleus might play an intermediary inhibitory role for rapid eye movement sleep reg ulation. Therefore, the effects of GABA or carbachol (a mixed cholinergic a gonist receptor) alone, as well as an agonist of one in presence of an anta gonist of the other, in the locus coeruleus were investigated on sleep-wake fulness and rapid eye movement sleep. The cholinergic agonist carbachol increased, while the muscarinic antagonis t receptor scopolamine decreased, the frequency of induction of rapid eye m ovement sleep per hour. In contrast, GABA and picrotoxin increased and decr eased, respectively, the duration of rapid eye movement sleep per episode. However, when carbachol was injected in the presence of picrotoxin or GABA was injected in the presence of scopolamine, the effect of GABA or picrotox in was dominant. Microinjection of both scopolamine and picrotoxin in combi nation reduced both the frequency of initiation as well as the duration per episode of rapid eye movement sleep. From these results we suggest that in the locus coeruleus cholinergic input modulates the frequency of induction of rapid eye movement sleep and this action is mediated through GABA interneurons, whereas the length of rapid e ye movement sleep per episode is maintained by the presence of an optimum l evel of GABA. A model of neural connections for initiation and maintenance of rapid eye movement sleep is proposed and discussed. (C) 2001 IBRO. Publi shed by Elsevier Science Ltd. All rights reserved.