Dr. Claire Gizowski – McGill University
Claire Gizowski & Charles W. Bourque (2020) Sodium regulates clock time and output via an excitatory GABAergic pathway. Nature, 583, 421-424 https://www.nature.com/articles/s41586-020-2471-x
Salt-sensitive neurons can affect the brain’s master clock time
Research by Drs. Claire Gizowski and Charles Bourque is the first to show that an injection of salt can activate neurons in the brain’s master clock in mice. Though light is a well know regulator of this clock, this is the first demonstration that another physiologically relevant cue can alter the timing of the body’s central clock. These results could lead to new research avenues to help travellers with jet-lag or shift workers whose internal clock is out of sync with their daily activities.
In this study, Drs. Claire Gizowski and Charles Bourque showed that mice injected with salt during the dark phase of the circadian cycle (corresponding to night) experience a reduction of core body temperature caused by deactivation of non-shivering heat production. This response was associated with an activation of clock neurons in the brain region considered to be the brain’s master clock, called the suprachiasmatic nucleus (SCN). These neurons are normally inactive during the night. A combination of anatomical and electrophysiological experiments revealed a novel brain circuit whereby salt-sensing neurons in a brain region called the OVLT relay the occurrence of a salt load to neurons in the brain’s central clock during the dark period. Remarkably, they found that a single salt injection shifted the time onset of activity observed on subsequent days in mice kept in constant darkness, and this effect could be mimicked or prevented by manipulating the new brain circuit the researcher had identified.
Recent studies have shown that shift-work, which causes a misalignment of daily activity and the natural circadian cycle, can increase the risk of many diseases including cancer, as well as cerebrovascular and neurodegenerative diseases. It is therefore of paramount importance that we increase our fundamental understanding of how the brain’s circadian clock is regulated. Indeed, this study demonstrates that something as innocuous as a salt pill could potentially be used to facilitate realignment of the circadian clock following jet-lag or shift-work and have the potential to significantly reduce disease risks. This paradigm shifting study demonstrates the clock is instructed about physiological need and can acutely alter its output to cope with dynamic changes in an organism’s internal environment. Indeed, these findings reveal that the clock is much more than a simple pacemaker, as previously thought.
Dr. Claire Gizowski
Dr. Gizowski performed all the experiments, analysis and preparation of figures reported in this paper. The study was co-designed and the manuscript co-written with Dr. Bourque (equal contributions). The study was entirely performed during Dr. Gizowski’s PhD training with Dr. Bourque at McGill University. Dr. Gizowski received her PhD in February 2020 and is now a post-doctoral fellow at the University of California in San Francisco (https://profiles.ucsf.edu/claire.gizowski).
This work was supported by a Foundation Grant from the Canadian Institutes of Health Research and a James McGill Chair to Charles Bourque., and a CIHR Banting and Best Canada Graduate Scholarship awarded to Claire Gizowski. The RIMUHC receives generous funding from the Fonds de Recherche Québec Santé.
Watch Claire Gizowski explain her work in a CAN trainee research feature