title: Altered rapid eye movement sleep timing in serotonin transporter knockout mice.
abstract: The monoamine neurotransmitter serotonin has long been implicated in development and maintenance of sleep patterns, yet the role of the serotonin transporter (SERT) in these processes has not been evaluated in detail. We report that genetically engineered SERT knockout mice exhibit more REM sleep (REMS) than wild type littermates (11 vs 7% of recording time under baseline conditions) and display more frequent REMS bouts that last longer. This phenotype resembles the previously reported long-term effect of repeated treatment with SERT inhibitor compounds rather than the acute REMS suppressing effect of treatment with such compounds, and is thus likely to reflect neuroadaptations to the absence of SERT, rather than an acute effect of its absence in the adult. While electroencephalographic (EEG) spectra did not differ between SERT knockout and wild type mice during non-REM sleep (NREMS) or REMS, the dynamics of the EEG during the transition from NREMS to REMS differed between the genotypes. The surge in EEG power in both the 6-9 Hz and 10-16 Hz ranges that occurs just prior to the onset of REMS (pre-REMS power surge) is of greater magnitude in SERT knockout mice than in wild type littermate controls. This observation contrasts with the reduced magnitude pre-REMS power surge observed in rats subjected to REMS deprivation relative to yoked controls. These results indicate that the pre-REMS power surge is influenced by REMS history and by monoaminergic transmission. Genetic differences in serotonin systems and developmental exposure to SERT blockers are likely to exert effects on REMS.
authors.affiliation: Sleep and Circadian Neurobiology Laboratory, Department of Psychiatry and Behavioral Sciences, Stanford University, Palo Alto, CA 94304, USA. jwisor@stanford.edu
authors.forename: J P
authors.initials: JP
authors.lastname: Wisor
authors.forename: S W
authors.initials: SW
authors.lastname: Wurts
authors.forename: F S
authors.initials: FS
authors.lastname: Hall
authors.forename: K P
authors.initials: KP
authors.lastname: Lesch
authors.forename: D L
authors.initials: DL
authors.lastname: Murphy
authors.forename: G R
authors.initials: GR
authors.lastname: Uhl
authors.forename: D M
authors.initials: DM
authors.lastname: Edgar
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000235:genetics; D004569:Electroencephalography / Q000379:methods; D005260:Female; D008297:Male; D008562:Membrane Glycoproteins / Q000172:deficiency* / Q000235:genetics; D026901:Membrane Transport Proteins; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins; D051381:Rats; D050486:Serotonin Plasma Membrane Transport Proteins; D012895:Sleep, REM / Q000235:genetics* / Q000502:physiology
chemical_list: D002352:Carrier Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D050486:Serotonin Plasma Membrane Transport Proteins; C493231:Slc6a4 protein, mouse; C493232:Slc6a4 protein, rat