Somatostatin-expressing interneurons induce early NO-driven and late specific astrocyte-mediated vasodilation

Abstract Somatostatin-expressing (SST) interneurons modulate hemodynamic responses both directly and indirectly, but their precise role remains unclear. Here, we investigated the influence of SST interneurons on hemodynamic control in response to optogenetic stimulation of SST neurons and somatosens...

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Main Authors: Thanh Tan Vo, Won Beom Jung, Tong Jin, Geun Ho Im, Soohyun Lee, Seong-Gi Kim
Format: Article
Language:English
Published: Nature Portfolio 2025-07-01
Series:Nature Communications
Online Access:https://doi.org/10.1038/s41467-025-61771-5
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author Thanh Tan Vo
Won Beom Jung
Tong Jin
Geun Ho Im
Soohyun Lee
Seong-Gi Kim
author_facet Thanh Tan Vo
Won Beom Jung
Tong Jin
Geun Ho Im
Soohyun Lee
Seong-Gi Kim
author_sort Thanh Tan Vo
collection DOAJ
description Abstract Somatostatin-expressing (SST) interneurons modulate hemodynamic responses both directly and indirectly, but their precise role remains unclear. Here, we investigated the influence of SST interneurons on hemodynamic control in response to optogenetic stimulation of SST neurons and somatosensory stimulation in both awake and anesthetized mice. Prolonged optogenetic stimulation of SST neurons induces fast vasodilation through nitric oxide synthase-expressing neurons that co-express SST, and slow vasodilation mediated by astrocytes. Similar neurovascular coupling mechanisms are observed during prolonged sensory stimulation, which also induces both fast and delayed vasodilation. The delayed vasodilation, mediated by the SST neuron-astrocyte pathway, enhances the specificity of cerebral blood volume (CBV)-weighted fMRI signals to cortical layer 4, as confirmed by chemogenetic inhibition of SST neurons. Our findings indicate that the SST neuron-astrocyte-vascular pathway shapes hemodynamic responses to prolonged stimulation and is critical for achieving high-specificity, laminar-resolution fMRI, which is increasingly pursued in human cognitive studies.
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spelling doaj-art-2e5b5105177d4686ab52599ca4cfbe0f2025-08-20T03:05:10ZengNature PortfolioNature Communications2041-17232025-07-0116112210.1038/s41467-025-61771-5Somatostatin-expressing interneurons induce early NO-driven and late specific astrocyte-mediated vasodilationThanh Tan Vo0Won Beom Jung1Tong Jin2Geun Ho Im3Soohyun Lee4Seong-Gi Kim5Center for Neuroscience Imaging Research (CNIR), Institute for Basic Science (IBS)Emotion, Cognition & Behavior Research Group, Korean Brain Research Institute (KBRI)Center for Neuroscience Imaging Research (CNIR), Institute for Basic Science (IBS)Center for Neuroscience Imaging Research (CNIR), Institute for Basic Science (IBS)Unit on Functional Neural Circuits, Systems Neurodevelopment Laboratory, National Institutes of HealthCenter for Neuroscience Imaging Research (CNIR), Institute for Basic Science (IBS)Abstract Somatostatin-expressing (SST) interneurons modulate hemodynamic responses both directly and indirectly, but their precise role remains unclear. Here, we investigated the influence of SST interneurons on hemodynamic control in response to optogenetic stimulation of SST neurons and somatosensory stimulation in both awake and anesthetized mice. Prolonged optogenetic stimulation of SST neurons induces fast vasodilation through nitric oxide synthase-expressing neurons that co-express SST, and slow vasodilation mediated by astrocytes. Similar neurovascular coupling mechanisms are observed during prolonged sensory stimulation, which also induces both fast and delayed vasodilation. The delayed vasodilation, mediated by the SST neuron-astrocyte pathway, enhances the specificity of cerebral blood volume (CBV)-weighted fMRI signals to cortical layer 4, as confirmed by chemogenetic inhibition of SST neurons. Our findings indicate that the SST neuron-astrocyte-vascular pathway shapes hemodynamic responses to prolonged stimulation and is critical for achieving high-specificity, laminar-resolution fMRI, which is increasingly pursued in human cognitive studies.https://doi.org/10.1038/s41467-025-61771-5
spellingShingle Thanh Tan Vo
Won Beom Jung
Tong Jin
Geun Ho Im
Soohyun Lee
Seong-Gi Kim
Somatostatin-expressing interneurons induce early NO-driven and late specific astrocyte-mediated vasodilation
Nature Communications
title Somatostatin-expressing interneurons induce early NO-driven and late specific astrocyte-mediated vasodilation
title_full Somatostatin-expressing interneurons induce early NO-driven and late specific astrocyte-mediated vasodilation
title_fullStr Somatostatin-expressing interneurons induce early NO-driven and late specific astrocyte-mediated vasodilation
title_full_unstemmed Somatostatin-expressing interneurons induce early NO-driven and late specific astrocyte-mediated vasodilation
title_short Somatostatin-expressing interneurons induce early NO-driven and late specific astrocyte-mediated vasodilation
title_sort somatostatin expressing interneurons induce early no driven and late specific astrocyte mediated vasodilation
url https://doi.org/10.1038/s41467-025-61771-5
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