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Cholinergic basal forebrain neurons regulate vascular dynamics and cerebrospinal fluid flux

Author

Listed:
  • Kai-Hsiang Chuang

    (The University of Queensland)

  • Xiaoqing Alice Zhou

    (The University of Queensland)

  • Ying Xia

    (CSIRO Health and Biosecurity)

  • Zengmin Li

    (The University of Queensland)

  • Lei Qian

    (The University of Queensland)

  • Eamonn Eeles

    (The University of Queensland)

  • Grace Ngiam

    (The University of Queensland)

  • Jurgen Fripp

    (CSIRO Health and Biosecurity)

  • Elizabeth J. Coulson

    (The University of Queensland
    The University of Queensland)

Abstract

Brain waste is cleared via a cerebrospinal fluid (CSF) pathway, the glymphatic system, whose dysfunction may underlie many brain conditions. Previous studies show coherent vascular oscillation, measured by blood oxygenation level-dependent (BOLD) fMRI, couples with CSF inflow to drive fluid flux. Yet, how this coupling is regulated, whether it mediates waste clearance, and why it is impaired remain unclear. Here we demonstrate that cholinergic neurons modulate BOLD-CSF coupling and glymphatic function. We find BOLD-CSF coupling correlates cortical cholinergic activity in aged humans. Lesioning basal forebrain cholinergic neurons in female mice impairs glymphatic efflux and associated changes in BOLD-CSF coupling, arterial pulsation and glymphatic influx. An acetylcholinesterase inhibitor alters these dynamics, primarily through peripheral mechanisms. Our results suggest cholinergic loss impairs glymphatic function by a neurovascular mechanism, potentially contributing to pathological waste accumulation. This may provide a basis for developing diagnostics and treatments for glymphatic dysfunction.

Suggested Citation

  • Kai-Hsiang Chuang & Xiaoqing Alice Zhou & Ying Xia & Zengmin Li & Lei Qian & Eamonn Eeles & Grace Ngiam & Jurgen Fripp & Elizabeth J. Coulson, 2025. "Cholinergic basal forebrain neurons regulate vascular dynamics and cerebrospinal fluid flux," Nature Communications, Nature, vol. 16(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-60812-3
    DOI: 10.1038/s41467-025-60812-3
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