Journal
NEURON
Volume 108, Issue 3, Pages 436-+Publisher
CELL PRESS
DOI: 10.1016/j.neuron.2020.07.015
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Funding
- China Postdoctoral Science Foundation [KLF101846]
- Development Project of Shanghai Peak Disciplines-Integrated Medicine [20150407]
- China Scholarship Council (CSC) [201609110039]
- Boston Children's Hospital IDDRC [1U54HD090255]
- NIH [R01AT010629]
- Harvard/MIT Joint Research Program in Basic Neuroscience
- Wellcome Trust [200183/Z/15/Z]
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The neuroanatomical basis behind acupuncture practice is still poorly understood. Here, we used intersectional genetic strategy to ablate NPY+ noradrenergic neurons and/or adrenal chromaffin cells. Using endotoxin-induced systemic inflammation as a model, we found that electroacupuncture stimulation (ES) drives sympathetic pathways in somatotopy- and intensity-dependent manners. Low-intensity ES at hindlimb regions drives the vagal-adrenal axis, producing anti-inflammatory effects that depend on NPY+ adrenal chromaffin cells. High-intensity ES at the abdomen activates NPY+ splenic noradrenergic neurons via the spinal-sympathetic axis; these neurons engage incoherent feedforward regulatory loops via activation of distinct adrenergic receptors (ARs), and their ES-evoked activation produces either anti- or pro-inflammatory effects due to disease-state-dependent changes in AR profiles. The revelation of somatotopic organization and intensity dependency in driving distinct autonomic pathways could form a road map for optimizing stimulation parameters to improve both efficacy and safety in using acupuncture as a therapeutic modality.
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