Jason Rihel, Professor of Behavioural Genetics at the Research Department for Cell and Developmental Biology, has been awarded a €3.5M ERC Advanced Grant to study one of neuroscience’s most fundamental challenges: how sleep alters synapses, the connections between brain cells. The research programme, entitled “Synapse Dynamics Across Sleep–Wake States,” will investigate how the brain reorganises itself during sleep and why this process is crucial for healthy brain function.
Sleep is essential to life, yet scientists still don’t fully understand its core purpose. One leading idea, the synaptic homeostasis hypothesis, proposes that sleep serves to normalise the strength and number of synapses that accumulate during wakefulness. The newly funded programme aims to uncover the mechanisms behind this process, using cutting-edge imaging and genetic tools in zebrafish.
The research team has already discovered that high levels of sleep pressure, the physiological drive to sleep that builds up the longer one stays awake, lead to more rapid elimination of synapses during sleep. In other words, when the need for sleep is greatest, such as at the start of the night or after sleep deprivation, the brain undergoes the most intense pruning of its synaptic connections.
“We found that only sleep periods with high sleep pressure, or with artificially elevated adenosine levels, support significant synaptic removal,” Prof Rihel explained. “Now we want to understand how that happens at the level of single neurons.”
The programme’s three main aims are to link synaptic changes to neuronal activity, explore how sleep pressure signals affect single neurons, and determine how these microscopic shifts in synapses influence sleep–wake behaviour. By integrating advanced imaging, genetics, and neurophysiology, the programme hopes to provide unprecedented insight into how the sleeping brain maintains balance and function following an energetically demanding period of wakefulness.
“Understanding how sleep pressure and neuronal activity interact to shape synaptic networks will bring us closer to explaining why sleep is indispensable,” says Prof Rihel. “Our zebrafish model gives us a unique window into these dynamics because we can observe single synapses in live animals.”
Beyond its fundamental scientific importance, this work could inform new approaches to treating sleep disorders and cognitive dysfunction.
Links
Key research article: Sleep pressure modulates single-neuron synapse number in zebrafish | Nature
Research briefing about Nature article: Built-up sleep pressure drives the loss of neuronal connections during slumber