Patrick Drew (right), professor of engineering science and mechanics, of biomedical engineering, of neurosurgery and of biology Credit: Kelby Hochreither/Penn State
Q&A: The neurology of slumbering whiskers
July 27, 2023
By Tim Schley
UNIVERSITY PARK, Pa. — Penn State researchers published a paper in Communications Biology finding that sleep-related changes to blood flow in the brains of neonatal mice far outweigh any caused by sensory stirrings. The results could help scientists better study and interpret signals from the brain, potentially leading to treatments for aging and disease.
The team is led by Patrick Drew, professor of engineering science and mechanics, of biomedical engineering, of neurosurgery and of biology; and Nanyin Zhang, Dorothy Foehr Huck and J. Lloyd Huck Chair in Brain Imaging. Co-authors include Qingguang Zhan, research assistant professor in engineering science and mechanics; graduate students Kevin L. Turner and Hayredding S. Ünsal from the College of Engineering; and graduate students Kyle W. Gheres and Xu Han from the Huck Institutes of the Life Sciences.
The paper is discussed in a Q&A with Drew below.
Q. Previously, you found that the “eye is the window” to know when a mouse is sleeping. In this study, you examined neurovascular coupling in neonatal mice and how it differed based on arousal state. What is neurovascular coupling, and why is it important to study?
Drew: When we are presented with a sensory stimulus — a touch or a sound, for example — neurons in the part of the brain that deals with that stimulus become more active, and the neurons send signals that cause nearby blood vessels to dilate, which is known as neurovascular coupling. These vascular changes are what are detectable using functional magnetic resonance imaging (fMRI), so understanding what they tell us about neural activity is important for interpreting fMRI signals. Normal neurovascular coupling is important for keeping the brain healthy, but we still don’t know why it exists.
Q. What would typically happen in a mouse’s brain when a pulse of air is blown on their whiskers? Would this change if they are sleeping? Did this differ in your study of neonatal mice?
Drew: Normally, when we stimulate the whiskers of a mouse, done by gently blowing a pulse of air toward the whiskers, we see an activation of neurons and a dilation of blood vessels in the somatosensory part of the brain, which helps perceive things like touch and body position.
Previous studies had suggested that neurovascular coupling was inverted in neonatal mice, but these studies did not track if the animals were awake or asleep. What we found in both neonates and in adults is that if the animal is asleep, the stimulation wakes them up, but because blood vessels are very dilated during sleep relative to the awake state, the net effect of stimulation in sleeping mice is constriction, rather than dilation. Neurovascular coupling was relatively normal in neonates compared to adults, but because they spent most of their time asleep, the average vascular response to whisker stimulation was basically the same as the average vascular response to awakening, which is constriction.
Q. What was your key takeaway?
Drew: Our arousal state — whether we are asleep or awake — is most important to determining how dilated the blood vessels are in the brain. Brain blood vessels are most dilated when we are asleep. The dilation of blood vessels will help increase blood flow and is thought to also help pump cerebrospinal fluid.
Our work shows it is very important to monitor arousal state in these types of studies. Much of the variability in animal response is due to arousal state fluctuations, and differences in behavior or neural responsiveness between groups might be caused by different their propensities to sleep. Luckily, there are many techniques to monitor and quantify behavioral state, including some developed by our lab.
Q. Where does the research go from here?
Drew: We are trying to understand which neurons and neuromodulators are causing blood vessels to dilate during sleep. Since the dilation and constriction of blood vessels is important for pumping waste out of the brain, understanding what brain components might be controlling this pumping is important for developing treatments for aging and neurodegenerative disease.
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