Differentially Timed Extracellular Signals Synchronize Pacemaker Neuron Clocks

Ben Collins, Harris S. Kaplan, Matthieu Cavey, Katherine R. Lelito, Andrew H. Bahle, Zhonghua Zhu, Ann Marie Macara, Gregg Roman, Orie T. Shafer, Justin Blau

Research output: Contribution to journalArticle

Abstract

Synchronized neuronal activity is vital for complex processes like behavior. Circadian pacemaker neurons offer an unusual opportunity to study synchrony as their molecular clocks oscillate in phase over an extended timeframe (24 h). To identify where, when, and how synchronizing signals are perceived, we first studied the minimal clock neural circuit in Drosophila larvae, manipulating either the four master pacemaker neurons (LNvs) or two dorsal clock neurons (DN1s). Unexpectedly, we found that the PDF Receptor (PdfR) is required in both LNvs and DN1s to maintain synchronized LNv clocks. We also found that glutamate is a second synchronizing signal that is released from DN1s and perceived in LNvs via the metabotropic glutamate receptor (mGluRA). Because simultaneously reducing Pdfr and mGluRA expression in LNvs severely dampened Timeless clock protein oscillations, we conclude that the master pacemaker LNvs require extracellular signals to function normally. These two synchronizing signals are released at opposite times of day and drive cAMP oscillations in LNvs. Finally we found that PdfR and mGluRA also help synchronize Timeless oscillations in adult s-LNvs. We propose that differentially timed signals that drive cAMP oscillations and synchronize pacemaker neurons in circadian neural circuits will be conserved across species.

Original languageEnglish (US)
JournalPLoS Biology
Volume12
Issue number9
DOIs
StatePublished - 2014

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Pacemakers
Neurons
oscillation
Clocks
neurons
receptors
Metabotropic Glutamate Receptors
glutamates
Networks (circuits)
Drosophila
Larva
Glutamic Acid
larvae
Proteins
proteins
Drive

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)
  • Neuroscience(all)
  • Medicine(all)

Cite this

Differentially Timed Extracellular Signals Synchronize Pacemaker Neuron Clocks. / Collins, Ben; Kaplan, Harris S.; Cavey, Matthieu; Lelito, Katherine R.; Bahle, Andrew H.; Zhu, Zhonghua; Macara, Ann Marie; Roman, Gregg; Shafer, Orie T.; Blau, Justin.

In: PLoS Biology, Vol. 12, No. 9, 2014.

Research output: Contribution to journalArticle

Collins, B, Kaplan, HS, Cavey, M, Lelito, KR, Bahle, AH, Zhu, Z, Macara, AM, Roman, G, Shafer, OT & Blau, J 2014, 'Differentially Timed Extracellular Signals Synchronize Pacemaker Neuron Clocks', PLoS Biology, vol. 12, no. 9. https://doi.org/10.1371/journal.pbio.1001959
Collins, Ben ; Kaplan, Harris S. ; Cavey, Matthieu ; Lelito, Katherine R. ; Bahle, Andrew H. ; Zhu, Zhonghua ; Macara, Ann Marie ; Roman, Gregg ; Shafer, Orie T. ; Blau, Justin. / Differentially Timed Extracellular Signals Synchronize Pacemaker Neuron Clocks. In: PLoS Biology. 2014 ; Vol. 12, No. 9.
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