New Insights into Brain Blood Flow Regulation by Inhibitory Neurons and Astrocytes

Researchers at the Center for Neuroscience Imaging Research within the Institute for Basic Science (IBS) have uncovered a novel two-step mechanism that explains how the brain precisely controls blood flow during neural activity. This discovery provides significant implications for interpreting functional magnetic resonance imaging (fMRI) results and advancing our understanding of neurovascular coupling.

Central to this process are somatostatin-expressing interneurons (SST neurons), a specialized group of inhibitory neurons that constitute about 15% of brain neurons. Previous research mainly focused on excitatory neurons, leaving the role of inhibitory neurons in regulating cerebral blood volume largely unexplored. The new study, published in Nature Communications, reveals how SST neurons interact with astrocytes—a type of support cell—to regulate blood vessel dilation and blood flow in specific brain regions.

Using innovative mouse models, such as SST-ChR2 and SST-hM4Di, the research team selectively activated or inhibited SST neurons. They employed advanced techniques including optogenetics, chemogenetics, calcium imaging, electrophysiology, and high-resolution imaging methods like intrinsic optical imaging and ultra-high-field fMRI. These methods allowed them to observe cellular activity, neural signals, and blood volume changes with remarkable precision.

The experiments demonstrated a two-phase vasodilation mechanism: initially, SST neurons release nitric oxide (NO), causing rapid dilation of nearby blood vessels, which explains the quick blood flow response during neural activation. Subsequently, astrocytes become activated, leading to a slower and localized vasodilation that sustains blood flow during prolonged neural activity.

A key finding was that silencing SST neurons abolished the spatial specificity of blood flow signals in fMRI, directly linking cellular activity to high-resolution imaging data. This illuminates how inhibitory neurons contribute to the fine spatial resolution observed in cortical layers during brain imaging.

The researchers also addressed technical challenges by combining multiple imaging techniques and conducting extensive repeat experiments to establish a causal relationship between SST activity and vascular responses. This work significantly advances the fundamental understanding of how neural activity influences blood flow and emphasizes the important role of inhibitory neurons and astrocytes.

Beyond basic science, these insights have clinical relevance. Disruptions in SST neuron functioning are implicated in neuropsychiatric and neurodegenerative conditions such as Alzheimer’s disease, depression, and autism. Future research aims to explore how these pathways are affected in disease models, paving the way for improved diagnostic and therapeutic strategies.

In conclusion, this study offers crucial new perspectives on the cellular mechanisms underlying neurovascular coupling, with potential impacts on brain imaging techniques, neuroscience research, and clinical applications.