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Differential Phase Arrangement of Cellular Clocks along the Tonotopic Axis of the Mouse Cochlea Ex Vivo

Park, Jung-sub; Cederroth, Christopher R.; Basinou, Vasiliki; Sweetapple, Lara; Buijink, Renate; Lundkvist, Gabriella B.; Michel, Stephan; Canlon, Barbara


Jung-sub Park

Christopher R. Cederroth

Vasiliki Basinou

Lara Sweetapple

Renate Buijink

Gabriella B. Lundkvist

Stephan Michel

Barbara Canlon


Topological distributions of individual cellular clocks have not been demonstrated in peripheral organs. The cochlea displays circadian patterns of core clock gene expression [1, 2]. PER2 protein is expressed in the hair cells and spiral ganglion neurons of the cochlea in the spiral ganglion neurons [1]. To investigate the topological organization of cellular oscillators in the cochlea, we recorded circadian rhythms from mouse cochlear explants using highly sensitive real-time tracking of PER2::LUC bioluminescence. Here, we show cell-autonomous and self-sustained oscillations originating from hair cells and spiral ganglion neurons. Multi-phased cellular clocks were arranged along the length of the cochlea with oscillations initiating at the apex (low-frequency region) and traveling toward the base (high-frequency region). Phase differences of 3 hr were found between cellular oscillators in the apical and middle regions and from isolated individual cochlear regions, indicating that cellular networks organize the rhythms along the tonotopic axis. This is the first demonstration of a spatiotemporal arrangement of circadian clocks at the cellular level in a peripheral organ. Cochlear rhythms were disrupted in the presence of either voltage-gated potassium channel blocker (TEA) or extracellular calcium chelator (BAPTA), demonstrating that multiple types of ion channels contribute to the maintenance of coherent rhythms. In contrast, preventing action potentials with tetrodotoxin (TTX) or interfering with cell-to-cell communication the broad-spectrum gap junction blocker (CBX [carbenoxolone]) had no influence on cochlear rhythms. These findings highlight a dynamic regulation and longitudinal distribution of cellular clocks in the cochlea.


Park, J., Cederroth, C. R., Basinou, V., Sweetapple, L., Buijink, R., Lundkvist, G. B., …Canlon, B. (2017). Differential Phase Arrangement of Cellular Clocks along the Tonotopic Axis of the Mouse Cochlea Ex Vivo. Current Biology, 27(17), 2623-2629.

Journal Article Type Article
Acceptance Date Jul 7, 2017
Online Publication Date Aug 17, 2017
Publication Date Sep 11, 2017
Deposit Date Nov 24, 2020
Journal Current Biology
Print ISSN 0960-9822
Electronic ISSN 1879-0445
Publisher Cell Press
Peer Reviewed Peer Reviewed
Volume 27
Issue 17
Article Number e2
Pages 2623-2629
Public URL
Publisher URL