Pet-1 deficiency alters the circadian clock and its temporal organization of behavior.
The serotonin and circadian systems are two important interactive regulatory networks in the mammalian brain that regulate behavior and physiology in ways that are known to impact human mental health. Previous work on the interaction between these two systems suggests that serotonin modulates photic input to the central circadian clock (the suprachiasmatic nuclei; SCN) from the retina and serves as a signal for locomotor activity, novelty, and arousal to shift the SCN clock, but effects of disruption of serotonergic signaling from the raphe nuclei on circadian behavior and on SCN function are not fully characterized. In this study, we examined the effects on diurnal and circadian behavior, and on ex vivo molecular rhythms of the SCN, of genetic deficiency in Pet-1, an ETS transcription factor that is necessary to establish and maintain the serotonergic phenotype of raphe neurons. Pet-1⁻/⁻ mice exhibit loss of rhythmic behavioral coherence and an extended daily activity duration, as well as changes in the molecular rhythms expressed by the clock, such that ex vivo SCN from Pet-1⁻/⁻ mice exhibit period lengthening and sex-dependent changes in rhythmic amplitude. Together, our results indicate that Pet-1 regulation of raphe neuron serotonin phenotype contributes to the period, precision and light/dark partitioning of locomotor behavioral rhythms by the circadian clock through direct actions on the SCN clock itself, as well as through non-clock effects.
Silvio O. Conte Center for Neuroscience Research, Vanderbilt University, Nashville, Tennessee, United States of America; Vanderbilt Brain Institute, Vanderbilt University, Nashville, Tennessee, United States of America.
Christopher M
CM
Ciarleglio
Silvio O. Conte Center for Neuroscience Research, Vanderbilt University, Nashville, Tennessee, United States of America; Vanderbilt Brain Institute, Vanderbilt University, Nashville, Tennessee, United States of America; Department of Biological Sciences, Vanderbilt University, Nashville, Tennessee, United States of America.
Holly E S
HE
Resuehr
Department of Biological Sciences, Vanderbilt University, Nashville, Tennessee, United States of America.
John C
JC
Axley
Department of Neuroscience, Case Western Reserve University, Cleveland, Ohio, United States of America.
Evan S
ES
Deneris
Silvio O. Conte Center for Neuroscience Research, Vanderbilt University, Nashville, Tennessee, United States of America; Vanderbilt Brain Institute, Vanderbilt University, Nashville, Tennessee, United States of America; Department of Biological Sciences, Vanderbilt University, Nashville, Tennessee, United States of America.
Douglas G
DG
McMahon
D000818:Animals; D001522:Behavior, Animal; D001921:Brain / Q000378:metabolism; D002940:Circadian Rhythm; D005260:Female; D005838:Genotype; D006579:Heterozygote; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009043:Motor Activity; D010641:Phenotype; D050783:Proto-Oncogene Proteins c-ets / Q000378:metabolism; D012160:Retina / Q000502:physiology; D059326:Serotonergic Neurons / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism; D015398:Signal Transduction; D013493:Suprachiasmatic Nucleus / Q000502:physiology*; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology*
C484684:Fev protein, mouse; D050783:Proto-Oncogene Proteins c-ets; D014157:Transcription Factors; D012701:Serotonin