The role of sleep in synaptic plasticity

Project Information

SleepSynapses

Grant agreement ID: 758580

DOI

10.3030/758580

Project closed

EC signature date 18 September 2017

Start date 1 February 2018

End date 31 January 2024

Funded under

• EXCELLENT SCIENCE - European Research Council (ERC)

Total cost

€ 1 706 250,00

EU contribution

€ 1 706 250,00

Coordinated by

VIB VZW
Belgium

Periodic Reporting for period 4 - SleepSynapses (The role of sleep in synaptic plasticity)

Reporting period: 2022-08-01 to 2024-01-31

Summary of the context and overall objectives of the project

Sleep is a fundamental and evolutionarily conserved behavior, and it remains the only primary behavior whose function is not fully understood. Despite its critical importance, sleep is relatively understudied within neuroscience. Understanding the function of sleep is also crucial for society due to its profound impact on health and well-being. Insights into the mechanisms of sleep can inform strategies to address sleep disorders, enhance cognitive function, and improve overall mental health and many neurological diseases.

This research project's primary objective is to determine sleep's function at the synaptic and cellular levels, as all brain processes and functions are rooted in the activities and dynamic properties of individual cells and synapses. My team and I utilized a novel genetic model for sleep-dependent plasticity that I established in the adult Drosophila brain to achieve this. Our goal was to elucidate the precise roles of sleep in synaptic plasticity, a topic currently under debate.

Our findings suggest that sleep supports critical processes of both homeostatic and Hebbian plasticity, thereby contributing to the maintenance and optimization of synaptic function. However, sleep-dependent homeostatic plasticity is not always the same form as the synaptic homeostasis hypothesis (SHY) proposed, down-scaling, but it is a novel, undescribable form of synaptic homeostasis.

Work performed from the beginning of the project to the end of the period covered by the report and main results achieved so far

This ERC Starting Grant has enabled me to establish a successful research group in a foreign country, attracting several highly motivated individuals worldwide. I have set up multiple state-of-the-art techniques at the host institute, enhancing our research capabilities.
We demonstrated that sleep promotes both homeostatic and Hebbian plasticity using electrophysiology approaches. Interestingly, the sleep-dependent homeostatic plasticity does not always conform to the form proposed by the synaptic homeostasis hypothesis (SHY). This novel form of sleep-dependent plasticity involves protein translation, specifically at synapses during sleep. We are currently working on publishing these novel findings.

By employing single-cell RNA sequencing, we also established the first single-cell transcriptome database of the adult fly brain across the sleep-wake cycle (Dopp et al., Nature Neuroscience, 2024). This comprehensive database, which provides valuable insights into the molecular mechanisms of sleep, is publicly available at https://www.flysleeplab.com/scsleepbrain

Additionally, we successfully developed the G-CLAMP system proposed in the project, with a significant design modification. We successfully labeled the local astrocytes near given synapses and funded the Ca2+ activities in these local astrocytes are important for sleep-dependent synaptic plasticity.

Our findings have significant implications for understanding the molecular and cellular mechanisms underlying sleep and its impact on synaptic plasticity. The establishment of a novel form of sleep-dependent homeostatic plasticity opens new avenues for research, challenging existing hypotheses and providing a fresh perspective on sleep's function.

Progress beyond the state of the art and expected potential impact (including the socio-economic impact and the wider societal implications of the project so far)

Our research has significantly advanced the field of sleep neuroscience by identifying a novel form of sleep-dependent homeostatic plasticity that challenges existing models, utilizing state-of-the-art electrophysiological techniques to elucidate the roles of sleep in synaptic plasticity, and establishing the first single-cell transcriptome database of the adult fly brain across the sleep-wake cycle. Additionally, we developed the G-CLAMP system to investigate the crucial role of Ca2+ activities in astrocytes for sleep-dependent synaptic plasticity. We have published some of these results, such as Dopp et al. in Nature Neuroscience (2024) and Blum et al. in Current Biology (2021). We are finalizing the other findings and plan to submit them to high-impact journals, thereby providing a comprehensive understanding of how sleep influences synapses and synaptic plasticity.

a sleeping fly