title: Activation of inactivation process initiates rapid eye movement sleep.
abstract: Interactions among REM-ON and REM-OFF neurons form the basic scaffold for rapid eye movement sleep (REMS) regulation; however, precise mechanism of their activation and cessation, respectively, was unclear. Locus coeruleus (LC) noradrenalin (NA)-ergic neurons are REM-OFF type and receive GABA-ergic inputs among others. GABA acts postsynaptically on the NA-ergic REM-OFF neurons in the LC and presynaptically on the latter's projection terminals and modulates NA-release on the REM-ON neurons. Normally during wakefulness and non-REMS continuous release of NA from the REM-OFF neurons, which however, is reduced during the latter phase, inhibits the REM-ON neurons and prevents REMS. At this stage GABA from substantia nigra pars reticulate acting presynaptically on NA-ergic terminals on REM-ON neurons withdraws NA-release causing the REM-ON neurons to escape inhibition and being active, may be even momentarily. A working-model showing neurochemical-map explaining activation of inactivation process, showing contribution of GABA-ergic presynaptic inhibition in withdrawing NA-release and dis-inhibition induced activation of REM-ON neurons, which in turn activates other GABA-ergic neurons and shutting-off REM-OFF neurons for the initiation of REMS-generation has been explained. Our model satisfactorily explains yet unexplained puzzles (i) why normally REMS does not appear during waking, rather, appears following non-REMS; (ii) why cessation of LC-NA-ergic-REM-OFF neurons is essential for REMS-generation; (iii) factor(s) which does not allow cessation of REM-OFF neurons causes REMS-loss; (iv) the association of changes in levels of GABA and NA in the brain during REMS and its deprivation and associated symptoms; v) why often dreams are associated with REMS.
authors.affiliation: School of Life Sciences, Jawaharlal Nehru University, New Delhi 110067, India. remsbnm@yahoo.com
authors.forename: Birendra Nath
authors.initials: BN
authors.lastname: Mallick
authors.forename: Abhishek
authors.initials: A
authors.lastname: Singh
authors.forename: Mudasir Ahmad
authors.initials: MA
authors.lastname: Khanday
mesh_terms: D059331:Adrenergic Neurons / Q000502:physiology*; D000818:Animals; D004325:Dreams / Q000502:physiology; D006801:Humans; D008125:Locus Coeruleus / Q000502:physiology*; D009433:Neural Inhibition / Q000502:physiology; D009638:Norepinephrine / Q000502:physiology*; D012895:Sleep, REM / Q000502:physiology*; D014851:Wakefulness / Q000502:physiology*; D005680:gamma-Aminobutyric Acid / Q000502:physiology*
chemical_list: D005680:gamma-Aminobutyric Acid; D009638:Norepinephrine