title: The homeostatic regulation of REM sleep: A role for localized expression of brain-derived neurotrophic factor in the brainstem.
abstract: Homeostatic regulation of REM sleep plays a key role in neural plasticity and deficits in this process are implicated in the development of many neuropsychiatric disorders. Little is known, however, about the molecular mechanisms that underlie this homeostatic regulation process. This study examined the hypothesis that, during selective REM sleep deprivation (RSD), increased brain-derived neurotrophic factor (BDNF) expression in REM sleep regulating areas is critical for the development of homeostatic drive for REM sleep, as measured by an increase in the number of REM sleep transitions. Rats were assigned to RSD, non-sleep deprived (BSL), or total sleep deprivation (TSD) groups. Physiological recordings were obtained from cortical, hippocampal, and pontine EEG electrodes over a 6h period, in which sleep deprivation occurred during the first 3h. In the RSD, but not the other conditions, homeostatic drive for REM sleep increased progressively. BDNF protein expression was significantly greater in the pedunculopontine tegmentum (PPT) and subcoeruleus nucleus (SubCD) in the RSD as compared to the TSD and BSL groups, areas that regulate REM sleep, but not in the medial preoptic area, which regulates non-REM sleep. There was a significant positive correlation between RSD-induced increases in number of REM sleep episodes and increased BDNF expression in the PPT and SubCD. These increases positively correlated with levels of homeostatic drive for REM sleep. These results, for the first time, suggest that selective RSD-induced increased expression of BDNF in the PPT and SubCD are determinant factors in the development of the homeostatic drive for REM sleep.
authors.affiliation: Department of Anesthesiology, Graduate School of Medicine, The University of Tennessee, 1924 Alcoa Highway, Knoxville, TN 37920, USA; Department of Psychology, College of Arts and Sciences, The University of Tennessee, 1404 Circle Drive, Knoxville, TN 37996, USA. Electronic address: sdatta1@utk.edu.
authors.forename: Subimal
authors.initials: S
authors.lastname: Datta
authors.affiliation: Department of Psychiatry, Boston University School of Medicine, 85 East Newton Street, Boston, MA 02118, USA.
authors.forename: Clifford M
authors.initials: CM
authors.lastname: Knapp
authors.affiliation: Department of Anesthesiology, Graduate School of Medicine, The University of Tennessee, 1924 Alcoa Highway, Knoxville, TN 37920, USA.
authors.forename: Richa
authors.initials: R
authors.lastname: Koul-Tiwari
authors.affiliation: Department of Anesthesiology, Graduate School of Medicine, The University of Tennessee, 1924 Alcoa Highway, Knoxville, TN 37920, USA.
authors.forename: Abigail
authors.initials: A
authors.lastname: Barnes
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism / Q000502:physiology; D001933:Brain Stem / Q000378:metabolism / Q000502:physiology*; D058256:Brain Waves; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism*; D004569:Electroencephalography; D006706:Homeostasis; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D012892:Sleep Deprivation / Q000378:metabolism; D012895:Sleep, REM / Q000502:physiology*; D014851:Wakefulness
chemical_list: D019208:Brain-Derived Neurotrophic Factor
keywords: BDNF; Brainstem; Dorsal subcoeruleus nucleus; Homeostatic regulation; Pedunculopontine tegmentum; Selective REM sleep deprivation