Pet-1 deficiency alters the circadian clock and its temporal organization of behavior.

Ciarleglio CM, Resuehr HE, Axley JC, Deneris ES, McMahon DG
PLoS One. 2014 9 (5): e97412

PMID: 24831114 · PMCID: PMC4022518 · DOI:10.1371/journal.pone.0097412

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.

MeSH Terms (20)

Animals Behavior, Animal Brain Circadian Rhythm Female Genotype Heterozygote Male Mice Mice, Inbred C57BL Mice, Transgenic Motor Activity Phenotype Proto-Oncogene Proteins c-ets Retina Serotonergic Neurons Serotonin Signal Transduction Suprachiasmatic Nucleus Transcription Factors

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