Differentially timed extracellular signals synchronize pacemaker neuron clocks.
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 perceive...
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2014
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oai:doaj.org-article:6146816d215240ffb0614f7fc84445f12021-11-25T05:32:56ZDifferentially timed extracellular signals synchronize pacemaker neuron clocks.1544-91731545-788510.1371/journal.pbio.1001959https://doaj.org/article/6146816d215240ffb0614f7fc84445f12014-09-01T00:00:00Zhttps://doi.org/10.1371/journal.pbio.1001959https://doaj.org/toc/1544-9173https://doaj.org/toc/1545-7885Synchronized 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.Ben CollinsHarris S KaplanMatthieu CaveyKatherine R LelitoAndrew H BahleZhonghua ZhuAnn Marie MacaraGregg RomanOrie T ShaferJustin BlauPublic Library of Science (PLoS)articleBiology (General)QH301-705.5ENPLoS Biology, Vol 12, Iss 9, p e1001959 (2014) |
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Biology (General) QH301-705.5 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 Differentially timed extracellular signals synchronize pacemaker neuron clocks. |
description |
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. |
format |
article |
author |
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 |
author_facet |
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 |
author_sort |
Ben Collins |
title |
Differentially timed extracellular signals synchronize pacemaker neuron clocks. |
title_short |
Differentially timed extracellular signals synchronize pacemaker neuron clocks. |
title_full |
Differentially timed extracellular signals synchronize pacemaker neuron clocks. |
title_fullStr |
Differentially timed extracellular signals synchronize pacemaker neuron clocks. |
title_full_unstemmed |
Differentially timed extracellular signals synchronize pacemaker neuron clocks. |
title_sort |
differentially timed extracellular signals synchronize pacemaker neuron clocks. |
publisher |
Public Library of Science (PLoS) |
publishDate |
2014 |
url |
https://doaj.org/article/6146816d215240ffb0614f7fc84445f1 |
work_keys_str_mv |
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