New Research Shows How Blood Gets to Where the Brain Needs It Most

When neurons in the brain are firing, they need energy—and they need it fast. But how the brain communicates with blood vessels to provide that energy has not been clear. Now, new researchexternal link, opens in a new tab led by HHMI Investigator Chenghua Gu shows direct signaling from neurons to the vasculature isn’t behind this infusion of fuel, as scientists previously thought. Instead, cells lining the brain’s blood vessels act as a signaling highway to control the rapid and coordinated flow of blood to active brain regions. The new work pinpoints how molecules and cells in these vessels work together to enable neurovascular coupling—a precisely regulated process crucial for the brain’s daily functioning and the foundation for functional brain imaging, an essential tool in medicine and science. During neurovascular coupling, neuronal activity triggers blood vessels in the brain to rapidly expand, increasing blood flow only to active regions without overtaxing the brain’s limited energy budget. However, studying neurovascular coupling in real-time has been challenging for researchers, hindering a deeper understanding about how it works on a cellular and molecular level. Using new methods to observe neurovascular coupling in active mice, Gu and her team at Harvard Medical Schoolexternal link, opens in a new tab discovered that brain endothelial cells, which line the inside of blood vessels, are connected by gap junctions—channels that facilitate fast cellular communication. They showed that signals traveling through these connections control how quickly and broadly blood vessels expand in response to neural activity. “This finding runs counter to the traditional view that neurons and astrocytes are major players in neurovascular coupling, illustrating that brain vasculature serves as a signaling highway to enable rapid and regional regulation of blood flow,” Gu says. The new findings could have immediate implications for functional Magnetic Resonance Imaging (fMRI), which relies on changes in blood flow in the brain to diagnose brain conditions, assist in brain surgeries, and advance research on brain function. A deeper understanding of how the brain regulates blood flow could enhance the interpretation and processing of fMRI data, according to the researchers. Additionally, the research could provide insights into the relationship between impaired neurovascular coupling and neurodegenerative diseases, shedding light on disease progression and potentially aiding in the development of new therapies. The innovative tools and methods developed by the team for studying the relationship between neuronal activity and vascular dynamics could also help other researchers study these connections in real time and space. They also could enable additional studies of gap junctions, which are found in nearly every cell in the body and orchestrate a wide range of physiological functions. “This new research not only allowed us to discover a new mechanism for neurovascular coupling,” says Gu, “but it will also set a new standard for the field to revisit old dogmas and open new lines of inquiry that were not previously possible.”