Roles of astroglial cells in sleep
We spend one third of our lives sleeping, yet we know surprisingly little about the reason why we sleep. It is believed that sleep is crucial for cognition, but also for housekeeping functions like repair and waste clearance. Decades of research have focused on neuronal activity during sleep. This research has shed light on primarily some of the cognitive functions supported by sleep. Yet, the roles of astroglial cells in these vital functions are mainly overlooked. We recently reported how astrocytes communicate during sleep, and that they are crucial for proper slow wave sleep (Bojarskaite et al. Nature Communications 2020, FOTS 11938). The purpose of this project is to further explore how astrocytes support the main functions of sleep, both cognitive, such as memory consolidation, and housekeeping, such as brain waste clearance.
The mice will be subjected to surgery for implantation of cranial windows, cisterna magna cannula and electrodes for registering brain waves and muscle activity, before being subjected to in vivo microscopy and sleep monitoring. The burden on the mice in relation to surgery is considered moderately severe, whereas the experiments cause little if any distress. The mice will fall asleep naturally while being head fixed, and hence have to be very comfortable with the experimental conditions.
Mechanisms uncovered by this project could have a profound impact on our knowledge on how sleep is regulated and what functions are supported by sleep. This knowledge will potentially enable us to treat sleep disorders in a more precise way in the future, but even more importantly shed knowledge on phsyiological mechanisms that are crucial for preventing brain disorders like Alzheimer's disease and Parkinson's disease.
The project involves altogether 1444 mice over 4 years, from altogether 18 substrains. The mice are bred in house (a separate in vitro locally approved FOTS application involves the breeding of these mice and with collaborator Reidun Torp and Evandro Fang). Two mouse lines ("floxed ReaChR-mCitrine X PDGFRβ-Cre" and "B6-Rosa-Flox-GCaMP6f") have not been imported form collaborative labs yet and will be included in in vitro locally approved FOTS application after import. Scientific works documenting that GA lines do not have a harmful phenotype were included in the local in vitro project.
This project will try to uncover completely unknown aspects of sleep and glial cell physiology in sleep. Hence, this knowledge cannot be attained by using in silico models or cell cultures or similar. The mice have cronic surgical implants, and data will be collected for several days from the same mouse. This will reduce the total number of mice needed. Our lab has extensive experience in in vivo two photon microscopy from the last 15 years and is the leading laboratory of its kind in Norway. We have extensive experience with the surgical procedures involved and all involved experimentalist undergo rigorous training to ensure surgeries of only top quality being performed.
The mice will be subjected to surgery for implantation of cranial windows, cisterna magna cannula and electrodes for registering brain waves and muscle activity, before being subjected to in vivo microscopy and sleep monitoring. The burden on the mice in relation to surgery is considered moderately severe, whereas the experiments cause little if any distress. The mice will fall asleep naturally while being head fixed, and hence have to be very comfortable with the experimental conditions.
Mechanisms uncovered by this project could have a profound impact on our knowledge on how sleep is regulated and what functions are supported by sleep. This knowledge will potentially enable us to treat sleep disorders in a more precise way in the future, but even more importantly shed knowledge on phsyiological mechanisms that are crucial for preventing brain disorders like Alzheimer's disease and Parkinson's disease.
The project involves altogether 1444 mice over 4 years, from altogether 18 substrains. The mice are bred in house (a separate in vitro locally approved FOTS application involves the breeding of these mice and with collaborator Reidun Torp and Evandro Fang). Two mouse lines ("floxed ReaChR-mCitrine X PDGFRβ-Cre" and "B6-Rosa-Flox-GCaMP6f") have not been imported form collaborative labs yet and will be included in in vitro locally approved FOTS application after import. Scientific works documenting that GA lines do not have a harmful phenotype were included in the local in vitro project.
This project will try to uncover completely unknown aspects of sleep and glial cell physiology in sleep. Hence, this knowledge cannot be attained by using in silico models or cell cultures or similar. The mice have cronic surgical implants, and data will be collected for several days from the same mouse. This will reduce the total number of mice needed. Our lab has extensive experience in in vivo two photon microscopy from the last 15 years and is the leading laboratory of its kind in Norway. We have extensive experience with the surgical procedures involved and all involved experimentalist undergo rigorous training to ensure surgeries of only top quality being performed.