Decoding neural circuits controlling sleep drive and sedation

Projektinformationen

DNCSS

ID Finanzhilfevereinbarung: 753548

DOI

10.3030/753548

Projekt abgeschlossen

EK-Unterschriftsdatum 6 März 2017

Startdatum 1 September 2018

Enddatum 31 August 2020

Finanziert unter

• EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions

Gesamtkosten

€ 183 454,80

EU-Beitrag

€ 183 454,80

Koordiniert durch

IMPERIAL COLLEGE OF SCIENCE TECHNOLOGY AND MEDICINE
United Kingdom

Periodic Reporting for period 1 - DNCSS (Decoding neural circuits controlling sleep drive and sedation)

Berichtszeitraum: 2018-09-01 bis 2020-08-31

Zusammenfassung vom Kontext und den Gesamtzielen des Projekts

Sleep is a universal behaviour across the animal kingdom and humans spend on average one-third of their lives asleep. Surprisingly, the full picture of how sleep is regulated and why we need sleep is still yet to be completed. In mammals, sleep consists of two phases: rapid eye movement (REM) sleep and non-rapid eye movement (NREM) sleep. Both REM and NREM sleep are chronologically and homeostatically regulated by several brain regions. Previous studies have established the association between sleep disturbances and almost all the neurological disorders, including autism, Alzheimer’s disease and Parkinson’s disease. In addition, sleep has also been compared to sedation, a state sharing significant behavioural similarities with sleep, such as reduced movements, enhanced slow-wave activity and lowered body temperature. Whether sedatives work through a common mechanism of hijacking the sleep-regulating circuits still remains elusive.

This project aimed to identify novel neuronal circuits controlling sleep and sedation. Discoveries of this project would significantly advance our understanding of the fundamental mechanisms of sleep/sedation and provide novel insights into how sleep is linked with various neurological disorders. It would also offer potential therapeutic strategies and contribute to designing more efficient and safer medications.

The main scientific goal was broken down into the following three objectives:
- To evaluate alterations of excitatory/inhibitory input onto defined LPO neurons during prolonged wakefulness and sedation.
- To identify the origin of inputs onto the defined LPO neurons
- To determine the effects of altered connectivity involving active LPO neurons on sleep and sedation status in vivo.

Arbeit, die ab Beginn des Projekts bis zum Ende des durch den Bericht erfassten Berichtszeitraums geleistet wurde, und die wichtigsten bis dahin erzielten Ergebnisse

Input and output brain regions of the LPO have been successfully mapped and several potential targets in the LPO circuits involved in sleep regulation have been identified. Two critical and novel regions were selected for further investigations during the course of the project. First, we have identified a novel REM-specific circuit wired from subcortical areas to the midbrain in the mammalian brain. The emotional stability was significantly compromised as a consequence of lacking REM sleep, providing novel evidence of why sleep is essential. Second, we captured sleep-pressure-responding neuronal ensembles located in the brainstem in vivo and further delineated their regulatory roles in NREM sleep and recovery sleep after sleep deprivation. In addition, our results revealed that sleep regulating neurons located in the midbrain contribute to mania-like behaviour. The findings of this project have been discussed in various scientific conferences/symposiums, departmental seminars, as well as college-organised events for engaging with the public.

Fortschritte, die über den aktuellen Stand der Technik hinausgehen und voraussichtliche potenzielle Auswirkungen (einschließlich der bis dato erzielten sozioökonomischen Auswirkungen und weiter gefassten gesellschaftlichen Auswirkungen des Projekts)

The findings of this project will offer novel insights into the mechanisms of sleep/sedation at the circuitry level. We are expecting to conduct further studies on other novel connecting areas of LPO identified in this project and hoping to obtain a more complete picture of how sleep is regulated. By designing and managing the project, the fellow has achieved a degree of professional maturation. After publishing all the data acquired in this project, the fellow will further build a competitive scientific profile for the next career stage. The results obtained during the funded period will also set important and new research directions for the fellow. Apart from the scientific impact, we were actively involved in College-organised events to engage with the public. Our research has attracted lots of attentions from the public, especially from the students in the British schools. We hope that by presenting our work and showing them around the lab, we would inspire younger generations to pursue science and make bigger impact for the society.

Schematic summary of the project