New live-imaging platform tracks how the brain keeps time

Researchers from Imperial College London have developed a new live imaging platform to study how the brain's internal clock works at the cellular level.

A project led by Dr Marco Ferrari and Dr Marco Brancaccio,  both from the Department of Brain Sciences at Imperial College London, is shedding new light on how the brain keeps time,  and how understanding this process could open new opportunities for treating neurodegenerative conditions such as Alzheimer's and Parkinson's. 

The brain's time-keeping process 

Published in Advanced Science, the study also reveals a previously unknown role for calcium in synchronising the brain's "master clock" – the suprachiasmatic nucleus (SCN), a tiny region in the hypothalamus that acts as the body's central timekeeper. 

Circadian clocks coordinate daily rhythms in gene expression, physiology and behaviour. In mammals, these rhythms depend on the SCN, which generates them through the coordinated activity of different cell types in brain tissue.  

Much of our current understanding comes from slower traditional methods or highly specialised custom-built microscopes available in only a handful of laboratories worldwide. 

As Dr Brancaccio explained, “Circadian rhythms are central to brain health but studying them in real time has been slow and technically challenging, which has limited this research to a handful of specialised laboratories worldwide.” 

Live tracking of the disease  

To overcome this, the researchers developed ClockCyte, a large-scale live imaging platform enabling continuous monitoring of circadian rhythms in up to 144 brain tissue samples simultaneously, across multiple fluorescent channels and over several weeks.

"From the outset, the goal was not just to solve our own challenges, but to open up this space to others and accelerate collaborative discovery," adds Dr Brancaccio. 

Using mouse SCN tissue, the team investigated a previously uncharacterised signal: calcium ions travelling along axons connecting neurons. They discovered that axonal calcium signals follow a 24-hour rhythm but behave very differently from calcium inside the cell body.

While internal calcium moves through tissue slowly in waves lasting several hours, axonal calcium travels in coordinated pulses that sweep instantly through the tissue, suggesting that axons may play a key role in synchronising the brain's daily rhythms.

The researchers also investigated the role of Bmal1 – the essential "clock gene" governing circadian processes in mammals, by removing it from SCN neurons. They found that its absence gradually disrupted the network organisation of axonal calcium signals: the tissue lost its structured connectivity, individual nerve fibres fell out of sync with one another, and the overall daily rhythm collapsed. 

The impact 

By adapting a commercially available imaging system and creating freely available analysis tools, the team has built a setup that is accessible, scalable and compatible with standardised laboratory workflows, producing more consistent, reproducible data than custom-built equipment. 

ClockCyte could also be adapted to study other neural circuits and tissues beyond the brain, opening the door to future research into how circadian rhythms contribute to health and disease across the body, with particular potential in dementia research, where disruption of sleep-wake cycles is a hallmark of Alzheimer's and other neurodegenerative conditions. 

More: 

• Link to the source (UKDRI).  
• Reference: M.Ferrari, N.Ness, J.Acosta, and M.Brancaccio, “A High-Throughput Live Imaging Platform to Investigate Circuit-Dependent Regulation of Circadian Rhythms in Brain Tissue.” Advanced Science (2026): e75427. https://doi.org/10.1002/advs.75427