Slowpoke functions in circadian output cells to regulate rest:activity rhythms.

The circadian system produces ~24-hr oscillations in behavioral and physiological processes to ensure that they occur at optimal times of day and in the correct temporal order. At its core, the circadian system is composed of dedicated central clock neurons that keep time through a cell-autonomous m...

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Autores principales:	Daniela Ruiz, Saffia T Bajwa, Naisarg Vanani, Tanvir A Bajwa, Daniel J Cavanaugh
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/b583b59cdbcf47828625eaf99c8b16d6
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spelling	oai:doaj.org-article:b583b59cdbcf47828625eaf99c8b16d62021-11-25T06:19:24ZSlowpoke functions in circadian output cells to regulate rest:activity rhythms.1932-620310.1371/journal.pone.0249215https://doaj.org/article/b583b59cdbcf47828625eaf99c8b16d62021-01-01T00:00:00Zhttps://doi.org/10.1371/journal.pone.0249215https://doaj.org/toc/1932-6203The circadian system produces ~24-hr oscillations in behavioral and physiological processes to ensure that they occur at optimal times of day and in the correct temporal order. At its core, the circadian system is composed of dedicated central clock neurons that keep time through a cell-autonomous molecular clock. To produce rhythmic behaviors, time-of-day information generated by clock neurons must be transmitted across output pathways to regulate the downstream neuronal populations that control the relevant behaviors. An understanding of the manner through which the circadian system enacts behavioral rhythms therefore requires the identification of the cells and molecules that make up the output pathways. To that end, we recently characterized the Drosophila pars intercerebralis (PI) as a major circadian output center that lies downstream of central clock neurons in a circuit controlling rest:activity rhythms. We have conducted single-cell RNA sequencing (scRNAseq) to identify potential circadian output genes expressed by PI cells, and used cell-specific RNA interference (RNAi) to knock down expression of ~40 of these candidate genes selectively within subsets of PI cells. We demonstrate that knockdown of the slowpoke (slo) potassium channel in PI cells reliably decreases circadian rest:activity rhythm strength. Interestingly, slo mutants have previously been shown to have aberrant rest:activity rhythms, in part due to a necessary function of slo within central clock cells. However, rescue of slo in all clock cells does not fully reestablish behavioral rhythms, indicating that expression in non-clock neurons is also necessary. Our results demonstrate that slo exerts its effects in multiple components of the circadian circuit, including PI output cells in addition to clock neurons, and we hypothesize that it does so by contributing to the generation of daily neuronal activity rhythms that allow for the propagation of circadian information throughout output circuits.Daniela RuizSaffia T BajwaNaisarg VananiTanvir A BajwaDaniel J CavanaughPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 16, Iss 3, p e0249215 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Daniela Ruiz Saffia T Bajwa Naisarg Vanani Tanvir A Bajwa Daniel J Cavanaugh Slowpoke functions in circadian output cells to regulate rest:activity rhythms.
description	The circadian system produces ~24-hr oscillations in behavioral and physiological processes to ensure that they occur at optimal times of day and in the correct temporal order. At its core, the circadian system is composed of dedicated central clock neurons that keep time through a cell-autonomous molecular clock. To produce rhythmic behaviors, time-of-day information generated by clock neurons must be transmitted across output pathways to regulate the downstream neuronal populations that control the relevant behaviors. An understanding of the manner through which the circadian system enacts behavioral rhythms therefore requires the identification of the cells and molecules that make up the output pathways. To that end, we recently characterized the Drosophila pars intercerebralis (PI) as a major circadian output center that lies downstream of central clock neurons in a circuit controlling rest:activity rhythms. We have conducted single-cell RNA sequencing (scRNAseq) to identify potential circadian output genes expressed by PI cells, and used cell-specific RNA interference (RNAi) to knock down expression of ~40 of these candidate genes selectively within subsets of PI cells. We demonstrate that knockdown of the slowpoke (slo) potassium channel in PI cells reliably decreases circadian rest:activity rhythm strength. Interestingly, slo mutants have previously been shown to have aberrant rest:activity rhythms, in part due to a necessary function of slo within central clock cells. However, rescue of slo in all clock cells does not fully reestablish behavioral rhythms, indicating that expression in non-clock neurons is also necessary. Our results demonstrate that slo exerts its effects in multiple components of the circadian circuit, including PI output cells in addition to clock neurons, and we hypothesize that it does so by contributing to the generation of daily neuronal activity rhythms that allow for the propagation of circadian information throughout output circuits.
format	article
author	Daniela Ruiz Saffia T Bajwa Naisarg Vanani Tanvir A Bajwa Daniel J Cavanaugh
author_facet	Daniela Ruiz Saffia T Bajwa Naisarg Vanani Tanvir A Bajwa Daniel J Cavanaugh
author_sort	Daniela Ruiz
title	Slowpoke functions in circadian output cells to regulate rest:activity rhythms.
title_short	Slowpoke functions in circadian output cells to regulate rest:activity rhythms.
title_full	Slowpoke functions in circadian output cells to regulate rest:activity rhythms.
title_fullStr	Slowpoke functions in circadian output cells to regulate rest:activity rhythms.
title_full_unstemmed	Slowpoke functions in circadian output cells to regulate rest:activity rhythms.
title_sort	slowpoke functions in circadian output cells to regulate rest:activity rhythms.
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/b583b59cdbcf47828625eaf99c8b16d6
work_keys_str_mv	AT danielaruiz slowpokefunctionsincircadianoutputcellstoregulaterestactivityrhythms AT saffiatbajwa slowpokefunctionsincircadianoutputcellstoregulaterestactivityrhythms AT naisargvanani slowpokefunctionsincircadianoutputcellstoregulaterestactivityrhythms AT tanvirabajwa slowpokefunctionsincircadianoutputcellstoregulaterestactivityrhythms AT danieljcavanaugh slowpokefunctionsincircadianoutputcellstoregulaterestactivityrhythms
_version_	1718413886523179008

Slowpoke functions in circadian output cells to regulate rest:activity rhythms.

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