Astrocytes regulate ultra-slow arteriole oscillations via stretch-mediated TRPV4-COX-1 feedback.

Jordan N Haidey,Minh Dang Nguyen,Milène Vandal,Kelsea A Gorzo,Wilten Nicola,Govind Peringod,Adam Institoris,Kenichi Ito,Frank Visser,Cameron Fielding,Grant R Gordon,Shiying Liu

doi:10.1016/j.celrep.2021.109405

Abstract

Very-low-frequency oscillations in microvascular diameter cause fluctuations in oxygen delivery that are important for fueling the brain and for functional imaging. However, little is known about how the brain regulates ongoing oscillations in cerebral blood flow. In mouse and rat cortical brain slice arterioles, we find that selectively enhancing tone is sufficient to recruit a TRPV4-mediated Ca2+ elevation in adjacent astrocyte endfeet. This endfoot Ca2+ signal triggers COX-1-mediated "feedback vasodilators" that limit the extent of evoked vasoconstriction, as well as constrain fictive vasomotion in slices. Astrocyte-Ptgs1 knockdown invivo increases the power of arteriole oscillations across a broad range of very low frequencies (0.01-0.3Hz), including ultra-slow vasomotion (∼0.1Hz). Conversely, clamping astrocyte Ca2+invivo reduces the power of vasomotion. These data demonstrate bidirectional communication between arterioles and astrocyte endfeet to regulate oscillatory microvasculature activity.

Highlights

Brain microvasculature constricts and dilates to control cerebral blood flow (CBF) at very low frequencies (0.01–0.3 Hz) in response to neural activity as well as systemic influences
Given the near constant nature of restingstate neural network rhythms, ultra-slow oscillations in CBF here may be responsible for supplying the brain with the majority of its energy requirements (Raichle, 2010) and are the physiological basis of computing functional connectivity via blood-oxygenlevel-dependent (BOLD) magnetic resonance imaging (He et al, 2018)
These processes are likely distinct from functional hyperemia, whereby CBF changes intermittently when neuronal activity increases above resting state, such as during sensation or performing a task

Summary

Introduction

Brain microvasculature constricts and dilates to control cerebral blood flow (CBF) at very low frequencies (0.01–0.3 Hz) in response to neural activity as well as systemic influences. Given the near constant nature of restingstate neural network rhythms, ultra-slow oscillations in CBF here may be responsible for supplying the brain with the majority of its energy requirements (Raichle, 2010) and are the physiological basis of computing functional connectivity via blood-oxygenlevel-dependent (BOLD) magnetic resonance imaging (He et al, 2018). These processes are likely distinct from functional hyperemia, whereby CBF changes intermittently when neuronal activity increases above resting state, such as during sensation or performing a task. This is important at parenchymal arterioles that display robust rhythmic diameter changes

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Conclusion