'The role of GABA signalling in the electrical timekeeping of the master circadian clock to drive circadian rhythms'

"Our daily or circadian body clock is one of the most important timing systems in our body, ensuring that our brain activity is appropriately aligned with our homeostatic, physiological, and behavioural needs across the day. This includes the timing in our sleep-wake cycle, peak cognition ability, and metabolic activity. Disruption of this daily rhythm can lead to severe health consequences, including premature ageing and mental health disorders.

In mammals, the master circadian clock is located in the hypothalamic suprachiasmatic nucleus (SCN). In the SCN, the activity of clock genes produces daily excitability rhythms in SCN neurons, causing them to spike at higher rates during the day with high intracellular calcium and less active at night with low intracellular calcium [1]. This daily rhythm in gene expression and electrical activity is vital for clock function, promoting well-being and good health.

GABA is the main neurotransmitter in the SCN and is critical for the generation of circadian rhythms [2]. Remarkably, although GABAergic signalling in the SCN is critical for our sense of daily rhythm, how GABA signals regulate SCN electrical and intracellular calcium activity remain poorly understood."