UMMS Affiliation

Department of Neurobiology; Emery Lab; Graduate School of Biomedical Sciences, Neuroscience Program

Date

2-10-2016

Document Type

Article

Disciplines

Neuroscience and Neurobiology

Abstract

Animals use circadian rhythms to anticipate daily environmental changes. Circadian clocks have a profound effect on behavior. In Drosophila, for example, brain pacemaker neurons dictate that flies are mostly active at dawn and dusk. miRNAs are small, regulatory RNAs ( approximately 22 nt) that play important roles in posttranscriptional regulation. Here, we identify miR-124 as an important regulator of Drosophila circadian locomotor rhythms. Under constant darkness, flies lacking miR-124 (miR-124(KO)) have a dramatically advanced circadian behavior phase. However, whereas a phase defect is usually caused by a change in the period of the circadian pacemaker, this is not the case in miR-124(KO) flies. Moreover, the phase of the circadian pacemaker in the clock neurons that control rhythmic locomotion is not altered either. Therefore, miR-124 modulates the output of circadian clock neurons rather than controlling their molecular pacemaker. Circadian phase is also advanced under temperature cycles, but a light/dark cycle partially corrects the defects in miR-124(KO) flies. Indeed, miR-124(KO) shows a normal evening phase under the latter conditions, but morning behavioral activity is suppressed. In summary, miR-124 controls diurnal activity and determines the phase of circadian locomotor behavior without affecting circadian pacemaker function. It thus provides a potent entry point to elucidate the mechanisms by which the phase of circadian behavior is determined.

SIGNIFICANCE STATEMENT: In animals, molecular circadian clocks control the timing of behavioral activities to optimize them with the day/night cycle. This is critical for their fitness and survival. The mechanisms by which the phase of circadian behaviors is determined downstream of the molecular pacemakers are not yet well understood. Recent studies indicate that miRNAs are important regulators of circadian outputs. We found that miR-124 shapes diurnal behavioral activity and has a striking impact on the phase of circadian locomotor behavior. Surprisingly, the period and phase of the neural circadian pacemakers driving locomotor rhythms are unaffected. Therefore, miR-124 is a critical modulator of the circadian output pathways that control circadian behavioral rhythms.

Rights and Permissions

Citation: J Neurosci. 2016 Feb 10;36(6):2007-13. doi: 10.1523/JNEUROSCI.3286-15.2016. Link to article on publisher's site

Comments

Co-authors Pallavi Lamba and Peiyi Guo are doctoral students in the Neuroscience Program in the Graduate School of Biomedical Sciences (GSBS) at UMass Medical School.

Publisher PDF posted after 12 months as allowed by the publisher's author rights policy at http://jneurosci.org/content/general-information#policies. Copyright of all material published in JNeurosci remains with the authors. The authors grant the Society for Neuroscience an exclusive license to publish their work for the first 6 months. After 6 months the work becomes available to the public to copy, distribute, or display under a Creative Commons Attribution 4.0 International (CC BY 4.0) license.

Related Resources

Link to Article in PubMed

Keywords

Drosophila, circadian behavior, circadian rhythms, miRNAs

PubMed ID

26865623

Creative Commons License

Creative Commons Attribution 4.0 License
This work is licensed under a Creative Commons Attribution 4.0 License.

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