The brain vascular activity has been recorded for the first time across the whole brain in rats during different sleep phases, using functional ultrasound imaging, a technique recently invented by the team Inserm U979 Wave Physics for Medicine. The study, conducted by the team of Mickael Tanter (Inserm U979 – Institut Langevin/CNRS/ESPCI Paris) in collaboration with the team of Ivan Cohen (Inserm UMR 8246 – Institut de Biologie Paris Seine/Université Pierre et Marie Curie), has resulted in unprecedented observations as reported this month in Nature Communications.
Functional ultrasound imaging is becoming the tool of choice to observe the cerebral activity and better understand the complex mechanisms involved in the brain. It enables to image the blood flows and their variations with an exquisite sensitivity and a very fine spatio-temporal resolution, while providing a field-of-view covering the entire brain (unlike other existing imaging modalities in fundamental neurosciences). Another major advantage over other neuroimaging methods resides in images being collected through a small probe placed on the rodent’s head without disturbing its activity, oppositely to MRI which requires the animal to stand still during the acquisition.
Brain activity of rats has been recorded during two wake states (quiet and active) and two sleep phases (rapid-eye-movement or REM, and non-REM). Analysis of the data reveals that while vascular activity is similar in non-REM sleep as in quiet wake, the activity is much higher in REM sleep than in active wake, and this across all regions of the brain. Mickael Tanter and Antoine Bergel have further discovered that the high activity in REM sleep consists of intense waves, coined “vascular surges”, propagating from the deep sub-cortical regions to the hippocampus before reaching the cortex; this pattern recurring several times within a 5 to 10-second period. Even more surprisingly, they have isolated a characteristic electric signal in the hippocampus (a key area in memory processes), preceding the vascular surges and enabling to predict their intensity. The latter information is crucial as it allows to identify the neuron type involved in the generation of these intense vascular phenomena, opening prospects for their regulation.
Functional ultrasound images (fUS) and electroencephalograms (EEG) recorded in a rat brain during wake, slow-wave sleep and rapid-eye-movement sleep. Unlike EEG signals which remain unchanged, fUS images show major differences of cerebral activity between wake and sleep states
These results are not only a great advance for understanding the link between the electrical and the vascular activity, it also reopens investigations on the role REM sleep which still remains unknown. The precursor electric signal suggests a strong link with memory, but the extent of vascular surges across the entire brain seems to play a more global regulation role, with a potential link with brain glymphatic clearance. These unprecedented functional ultrasound findings will soon be assessed in human neonates, and they already pave the way for understanding the regulation mechanisms involved in sleep and therefore developing therapeutic approaches for sleep disorders.