New in Neuroscience: Pericytes are Novel Players in Fueling the Brain
/The arteries and veins of the brain, via Wikimedia Commons.
The brain is a gas-guzzler. Weighing in at only 2% of the mass of your body, the brain consumes over 20% of the body’s energy. To get the energy needed for its constant computations, the brain thus requires an intricate and well-regulated blood supply that 1) provides the whole brain with constant food and oxygen and 2) ensures that any region of the brain that is in high demand gets the additional blood it needs. This regulation of blood supply by high-activity, high-demand neurons in your brain is termed “neurovascular coupling.” It is necessary for proper brain functioning and is the principle behind human neuroimaging techniques like PET and MRI.
Despite this, little is known about how neurons ask for more blood when they need it. Previous research suggested that cells known as astrocytes may be the primary mediators of neurovascular coupling. Astrocytes constantly sample the activity of neurons and are in direct contact with blood vessels, making them excellent candidates for the job. It was thought that astrocytes would sense neural activity and release factors onto the muscle cells that surround vessels to tell them to either dilate or contract. However, studies attempting to elucidate the role of astrocytes in regional blood supply found generally conflicting results, leading some scientists to suggest that a little-known cell type in the brain called a “pericyte” (distinct from parasite) may actually be at the root of neurovascular coupling. Initially, researchers found that pericytes could control the diameter of capillaries in the brain, wrapping thin processes around the blood vessels and cinching them tight like a drawstring bag to limit blood flow. But studies in live animals suggested that these diameter changes were dispensable for neurovascular coupling. Nevertheless, the lab of David Attwell at University College London recently published a paper in the academic journal Nature that puts the spotlight back on pericytes.
First, Attwell’s team confirmed that pericytes could indeed cause both dilation and constriction of capillaries in cultured brain slices. However, the researchers went further and showed that pericytes and capillaries contract in the functioning brains of living mice by tickling the mice’s whiskers and watching capillary and pericyte diameter changes in the corresponding area of the cortex. This showed that pericytes and capillaries were indeed changing in diameter in response to real-world brain activity, but to make Attwell’s pericytes-driven model of neurovascular coupling feasible, they had to make sure that the order of events checked out. Some researchers had suggested that big blood vessels in the brain actually regulate the blood flow to different areas and that the tiny capillaries just open or close due to changing pressure upstream, like a stream changing in width when the raging river that feeds it swells or shrinks. This would suggest that the diameter changes seen in pericytes on capillaries just happened passively due to some other mechanism that changes blood flow in larger vessels. However, Attwell’s lab showed that the capillaries changed in diameter before the larger upstream blood vessels, further suggesting that the capillary pericytes are the true mediators of neurovascular coupling.
Though this paper changes the focus and direction of the neurovascular coupling field, many questions remain. Most notably, though Attwell re-established pericytes as possible players in neurovascular coupling, he failed to establish true causality between pericytes constriction/dilation and blood vessel diameter changes in living brains. Future experiments will need to carefully piece apart the role of astrocytes vs pericytes in controlling blood flow as well as characterize how these processes change in disease. Only then will we understand how the gas-guzzling brain keeps its engine so finely tuned.
