Sleep resets brain connections for a few hours, but then what happens?

In a study involving zebrafish, a team of scientists led by the University College London (UCL) has explored how the brain manages synaptic connections during sleep. 

The experts found that the brain weakens new neural connections that were forged during waking hours, but this process only accounts for the first few hours of sleep. 

Function of sleep is still unclear 

“Although sleep is conserved across the animal kingdom, the precise functions of sleep remain unclear. As sleep deprivation leads to acute impairment of cognitive performance, many theories posit that synaptic plasticity associated with learning and memory preferentially occurs during sleep,” wrote the study authors. 

“For example, the synaptic homeostasis hypothesis (SHY) proposes that synaptic potentiation during wakefulness results in an ultimately unsustainable increase in synaptic strength and number that must be renormalized during sleep through synaptic weakening and pruning. Such sleep-dependent renormalization has been postulated to broadly affect most excitatory synapses throughout the brain.”

The synaptic homeostasis hypothesis

The findings support the synaptic homeostasis hypothesis, positing that sleep functions as a crucial reset mechanism for the brain, ensuring energy sustainability and readiness for new learning.

“Some studies examining either large neuronal populations or small patches of dendrites have found evidence consistent with the synaptic homeostasis hypothesis, but whether sleep merely functions as a permissive state or actively promotes synaptic downregulation at the scale of whole neurons is unclear,” wrote the researchers.

The brain goes offline

“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,” said senior author Jason Rihel, a professor in the UCL Cell & Developmental Biology department. 

“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 ‘offline’ period when those connections can be weakened across the brain, in preparation for us to learn new things the following day.”

Synaptic connections in the brain during sleep

The researchers used optically translucent zebrafish with genes that allow for easy imaging of synapses – the structures enabling communication between brain cells. 

“To examine the scope and selectivity of sleep-linked synaptic plasticity, it is vital to comprehensively track the synaptic changes of individual neurons through sleep-wake states,” wrote the study authors. 

“To that end, we used in vivo synaptic labeling tools in larval zebrafish to image the same neurons and their synapses repeatedly over long timescales, enabling us to map single-neuron synapse changes across sleep and wake states.”

Significant changes in the first half of the night

By observing these fish over multiple sleep-wake cycles, they discovered that synaptic connections increase during wakefulness and decrease during sleep, particularly when sleep was postponed, indicating that sleep pressure intensifies this reduction.

The study revealed that the significant synaptic changes primarily occur during the first half of the night, coinciding with the peak period of slow-wave activity, a critical phase of the sleep cycle.

Sleep dampens connections in the brain

“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,” said lead author Anya Suppermpool from UCL Cell & Developmental Biology and 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.”

This research not only deepens our understanding of sleep’s role in synaptic management but also poses new questions about the functions of its later stages, paving the way for future investigations into the full spectrum of sleep’s impact on brain health.

The study is published in the journal Nature.

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