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dc.contributor.authorBasnakova, Adrianaen_US
dc.contributor.authorCheng, Ruey-Kuangen_US
dc.contributor.authorChia, Joanne Shu Mingen_US
dc.contributor.authorD'Agostino, Giuseppeen_US
dc.contributor.authorTan, Germaine Jia Huien_US
dc.contributor.authorLangley, Sarah Rayeen_US
dc.contributor.authorJesuthasan, Sureshen_US
dc.identifier.citationBasnakova, A., Cheng, R., Chia, J. S. M., D'Agostino, G., Suryadi, Tan, G. J. H., Langley, S. R. & Jesuthasan, S. (2021). The habenula clock influences response to a stressor. Neurobiology of Stress, 15, 100403-.
dc.description.abstractThe response of an animal to a sensory stimulus depends on the nature of the stimulus and on expectations, which are mediated by spontaneous activity. Here, we ask how circadian variation in the expectation of danger, and thus the response to a potential threat, is controlled. We focus on the habenula, a mediator of threat response that functions by regulating neuromodulator release, and use zebrafish as the experimental system. Single cell transcriptomics indicates that multiple clock genes are expressed throughout the habenula, while quantitative in situ hybridization confirms that the clock oscillates. Two-photon calcium imaging indicates a circadian change in spontaneous activity of habenula neurons. To assess the role of this clock, a truncated clocka gene was specifically expressed in the habenula. This partially inhibited the clock, as shown by changes in per3 expression as well as altered day-night variation in dopamine, serotonin and acetylcholine levels. Behaviourally, anxiety-like responses evoked by an alarm pheromone were reduced. Circadian effects of the pheromone were disrupted, such that responses in the day resembled those at night. Behaviours that are regulated by the pineal clock and not triggered by stressors were unaffected. We suggest that the habenula clock regulates the expectation of danger, thus providing one mechanism for circadian change in the response to a stressor.en_US
dc.description.sponsorshipAgency for Science, Technology and Research (A*STAR)en_US
dc.description.sponsorshipMinistry of Education (MOE)en_US
dc.description.sponsorshipNanyang Technological Universityen_US
dc.description.sponsorshipNational Research Foundation (NRF)en_US
dc.relation.ispartofNeurobiology of Stressen_US
dc.rights© 2021 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (
dc.titleThe habenula clock influences response to a stressoren_US
dc.typeJournal Articleen
dc.contributor.schoolLee Kong Chian School of Medicine (LKCMedicine)en_US
dc.contributor.schoolSchool of Physical and Mathematical Sciencesen_US
dc.contributor.organizationInstitute of Molecular and Cell Biology, Singaporeen_US
dc.description.versionPublished versionen_US
dc.subject.keywordsCircadian Clocken_US
dc.description.acknowledgementThis work was funded by grants from the Singapore Ministry of Education under its Academic Research Fund Tier 2 (MOE2017-T2-058) and the National Research Foundation (NRF2017-NRF-ISF002-2676) to SJ and an ARAP fellowship from A*Star to AB. SRL was supported by the Lee Kong Chian School of Medicine and Nanyang Technological University Singapore Nanyang Assistant Professor Start-Up Grant, while GDA was supported by the Lee Kong Chian School of Medicine Dean’s Postdoctoral Fellowship.en_US
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