The blood flow in the brain constantly changes every time a person thinks or moves their body. These changes in blood flow serve as signals that indirectly show the activity state of the brain and are utilized in high-resolution brain imaging technology and neuroscience research. However, how these signals are generated and regulated at the level of individual cells has not yet been clearly established.
The Institute for Basic Science (IBS) announced on the 21st that a research team led by Director General Kim Seong-ki from Sungkyunkwan University, in collaboration with Senior Researcher Jeong Won-beom from the Korea Brain Research Institute, has discovered that inhibitory neurons play a key role in regulating brain blood flow.
The interaction between neural activity in the brain and blood flow responses is a fundamental basis for all brain functions that enable thoughts, sensations, and motor functions. The currently widely used functional magnetic resonance imaging (fMRI) technology is also based on this interaction principle.
Previously, it was known that excitatory neurons regulate blood flow, but the role of inhibitory neurons, which make up about 15% of all brain neurons, was not well understood. Among these, the function of somatostatin (SST) neurons, which constitute about 30%, remained largely unexplored. Somatostatin is an inhibitory neurotransmitter produced in the brain and body that regulates the activity of other neurons and suppresses neural signals.
The research team confirmed that SST neurons regulate brain blood flow through a two-step mechanism of vasodilation. First, they rapidly dilate blood vessels through the secretion of nitric oxide, followed by the activation of astrocytes, brain cells that support neurons, inducing a slower but sustained expansion of blood vessels.
The researchers observed the responses of neurons, blood flow, and astrocytes when they optogenetically and sensory stimulated the SST neurons in experimental mice. As a result, they revealed that stimulating the SST neurons rapidly secretes nitric oxide, causing blood vessels to dilate, and subsequently activates astrocytes, promoting slower but sustained blood vessel expansion through a "neuron-glial-vascular coupling pathway."
Recently, in the field of brain imaging, ultra-high-resolution layer fMRI technology has gained attention for its ability to precisely analyze functional differences by cortical depth. It is considered an innovative tool for visualizing subtle differences that were difficult to detect with existing imaging methods; however, it remains unclear what cells or vascular actions the observed signals are based on, leading to limitations in interpretation.
In this experiment, when the function of SST neurons was blocked, a significant reduction in the specificity of layer fMRI signals was observed. This indicates that the pathway in which SST neurons and astrocytes work together plays a crucial role in forming the spatial precision of brain vascular responses.
Thus, the research team revealed for the first time that SST neurons directly participate in the regulation of brain blood flow, and that delayed vascular expansion mediated by astrocytes forms a major cellular mechanism for layer fMRI signal specificity.
This discovery is expected to contribute to enhancing the interpretive power of high-resolution brain imaging technology by providing the physiological basis for layer fMRI signals. It has also opened up possibilities for improving the precision of brain disease imaging analysis and early diagnosis.
Director General Kim Seong-ki noted, "This study demonstrates the sophisticated interaction between inhibitory neurons and astrocytes as a key mechanism in regulating brain blood flow," expressing hope that it will contribute meaningfully to human cognitive function research, brain disease diagnosis strategies, and high-precision brain imaging technology development. The results of this study were published online in the international journal 'Nature Communications' on the 18th.
References
Nature Communications (2025), DOI: https://doi.org/10.1038/s41467-025-61771-5