A recent study has provided new insights into the complex role of sleep in brain function. Conducted on zebrafish, the research revealed that during the first half of a night’s sleep, the brain weakens the new connections between neurons formed while awake. However, this process does not continue into the second half of the night, leaving open questions about the latter stage’s purpose. Published in the journal Nature, the study supports the Synaptic Homeostasis Hypothesis, which suggests sleep serves as a reset for the brain.
The exact function of sleep has long puzzled scientists. While it is known that sleep is crucial for cognitive performance, its precise role at the neuronal level remains unclear. One prevailing theory is the Synaptic Homeostasis Hypothesis, which posits that sleep helps balance the strengthening and weakening of synapses (connections between neurons) that occur during waking hours. This balance is essential because continuous strengthening of synapses would be energetically unsustainable and could impede the formation of new connections needed for learning. The researchers aimed to test this hypothesis by observing the synaptic changes that occur during sleep in zebrafish.
To explore these changes, researchers used optically translucent zebrafish with genetically modified brains that allowed easy imaging of synapses. They monitored the fish over several sleep-wake cycles to observe how synaptic connections evolved. Specifically, they tracked the changes in synapse numbers and strengths across different phases of the day and night.
The zebrafish were chosen for their transparency, which enabled detailed imaging of brain structures. The researchers used a synapse labelling system that highlights synaptic proteins, allowing them to visualize the connections between neurons in real-time. They then subjected the fish to varying sleep conditions, including sleep deprivation, to see how these conditions affected synapse dynamics.
The study found that during waking hours, brain cells gained more connections, which were then pruned during sleep. This pruning was more pronounced during the first half of the night. This pattern aligns with the period of slow-wave sleep, which is known to be more intense at the beginning of the night. When the fish were deprived of sleep, their synaptic connections continued to grow until they were finally allowed to rest, after which pruning resumed.
“Our findings add weight to the theory that sleep serves to dampen connections within the brain, preparing for more learning and new connections again the next day,” explained first author Anya Suppermpool, a postdoctoral researcher in the Andres lab at UCL Ear Institute. “But our study doesn’t tell us anything about what happens in the second half of the night. There are other theories around sleep being a time for clearance of waste in the brain, or repair for damaged cells – perhaps other functions kick in for the second half of the night.”
Interestingly, the study noted that this synaptic pruning was less effective during shorter, mid-day naps, likely due to lower sleep pressure (the body’s need for sleep). This suggests that the benefits of sleep on synapse pruning are more significant during longer, nightly sleep periods when sleep pressure is higher.
The researchers also found variability in synaptic changes among different types of neurons. Some neurons showed a consistent pattern of synapse gain during the day and loss at night, while others displayed the opposite pattern. This variability suggests that different neuron types might have distinct roles or regulatory mechanisms during sleep.
University College London professor Jason Rihel said: “When we are awake, the connections between brain cells get stronger and more complex. If this activity were to continue unabated, it would be energetically unsustainable. Too many active connections between brain cells could prevent new connections from being made the following day.
“While the function of sleep remains mysterious, it may be serving as an ‘off-line’ period when those connections can be weakened across the brain, in preparation for us to learn new things the following day.”
While these findings provide valuable insights, it is not certain that they directly apply to humans. Human sleep is more complex, and the functions of different sleep stages may vary.
Additionally, the study focused primarily on the early stages of sleep and did not provide conclusive insights into what happens during the latter half of the night. The researchers suggest that other functions, such as clearing waste from the brain or repairing damaged cells, might be more active during this period. Further research is needed to explore these possibilities.
Future studies should also investigate the molecular mechanisms that drive synaptic pruning during sleep. Understanding these mechanisms could provide deeper insights into how sleep contributes to learning and memory. Moreover, examining how different types of neurons and brain regions are affected by sleep could help elucidate the broader role of sleep in brain function.
“If the patterns we observed hold true in humans, our findings suggest that this remodelling of synapses might be less effective during a mid-day nap, when sleep pressure is still low, rather than at night, when we really need the sleep,” Rihel said.
The study, “Sleep pressure modulates single-neuron synapse number in zebrafish,” was authored by Anya Suppermpool, Declan G. Lyons, Elizabeth Broom, and Jason Rihel.
