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The Synaptic Homeostasis Hypothesis suggests that when we are awake, the brain’s synapses (structures enabling communication between neurons) become overloaded through learning and experience. Sleep is thought to act as a reset button, shutting down synaptic activity to maintain balance and ensure the brain functions optimally.
Led by Sha Liu, assistant professor at VIB-KU Leuven’s Center for Brain & Disease Research, SleepSynapses employed advanced genetic models and cutting-edge technologies to explore how sleep influences these synaptic connections.
The SleepSynapses project was funded by the European Research Council.
Flies: the ideal subjects
Unlike traditional tests with mice, SleepSynapses focused on the genetic simplicity of fruit flies (Drosophila melanogaster). These organisms offer a unique advantage for scientific study, as researchers can analyse the same synapse across multiple conditions, something that is nearly impossible in the mammalian cortex. Using this approach, the team was able to precisely study synaptic changes induced by sleep and sleep deprivation.
This led to significant breakthroughs. Researchers employed single-cell transcriptomics to study how sleep and wakefulness influence the genetic activity of various brain cell types. The findings, published in ‘Nature Neuroscience’, found that glial cells – non-neuronal cells long considered support players – are vital in maintaining sleep homeostasis.
“Glial cells regulate sleep homeostasis in ways we hadn’t previously understood,” says Liu. “Their importance in the brain’s sleep-wake cycle highlights how much more we need to uncover about this overlooked aspect of neuroscience.”
Surprising discoveries
Synaptic plasticity is how we learn new things, form memories and adapt to experiences. The team found a new way that the brain keeps its synapses balanced. Instead of adjusting all synapses slowly, this newly discovered process works faster and focuses on specific connections, mainly on the sending side of neurons. This process happens while we’re awake, and seems to play a role in how brain activity, rest and learning are connected.
These findings contribute to a long-standing scientific debate by offering new perspectives on how sleep impacts neural function at the cellular level.
“It’s not just about downscaling everything during sleep,” Liu notes. “We see a more dynamic system where certain synapses are maintained or even strengthened, enabling memory and learning consolidation while still achieving overall balance.”
The project’s success was remarkable given the challenges it faced. Liu launched his FlySleepLab during the COVID-19 pandemic, where hiring delays, equipment shortages and disrupted supply chains added extra layers of complexity. Still, the team persevered, producing groundbreaking results and training up a new generation of early-stage researchers – all of whom have gone on to take up positions in academia.
Redefining sleep
Aside from redefining synaptic homeostasis, SleepSynapses has laid the groundwork for deeper research into the cellular mechanisms of sleep. “What does it mean for a cell to sleep? Or wake?” Liu asks. These questions, once relegated to the abstract, are now tangible objectives for future research.
Additionally, the project highlighted the importance of fundamental science. Current trends favour mammal-focused research, but Liu champions simpler testing models such as fruit flies. “Understanding basic mechanisms provides the foundation for everything else,” he remarks. “If we neglect this, we risk overlooking fundamental principles that drive more complex systems.”
Piecing together the puzzle
The findings from SleepSynapses are set to impact neuroscience broadly. Revealing how sleep balances brain activity and supports memory, the project’s work offers fresh perspectives on sleep disorders and cognitive health. As Liu puts it, “We’re closer than ever to understanding what sleep means, not just to us as individuals but to the cells that make up who we are.”
The mystery of why we sleep may not be solved just yet, but thanks to SleepSynapses, pieces of the puzzle are beginning to fall into place.