Somatotopic organization of autonomic reflexes by acupuncture.

Acupuncture has been practiced for more than 2000 years in China and now all over the world. One core idea behind this medical practice is that stimulation at specific body regions (acupoints) can distantly modulate organ physiology, but the underlying scientific basis has been long debated. Here, I summarize evidence supporting that long-distant acupuncture effects operate partly through somato-autonomic reflexes, leading to activation of sympathetic and/or parasympathetic pathways. I then discuss how the patterning of the somatosensory system along the rostro-caudal axis and the cutaneous-deep tissue axis might explain acupoint specificity and selectivity in driving specific autonomic pathways, particularly those modulating gastrointestinal motility and systemic inflammation.

A neuroanatomical basis for electroacupuncture to drive the vagal-adrenal axis.

Somatosensory autonomic reflexes allow electroacupuncture stimulation (ES) to modulate body physiology at distant sites1-6 (for example, suppressing severe systemic inflammation6-9). Since the 1970s, an emerging organizational rule about these reflexes has been the presence of body-region specificity1-6. For example, ES at the hindlimb ST36 acupoint but not the abdominal ST25 acupoint can drive the vagal-adrenal anti-inflammatory axis in mice10,11. The neuroanatomical basis of this somatotopic organization is, however, unknown. Here we show that PROKR2Cre-marked sensory neurons, which innervate the deep hindlimb fascia (for example, the periosteum) but not abdominal fascia (for example, the peritoneum), are crucial for driving the vagal-adrenal axis. Low-intensity ES at the ST36 site in mice with ablated PROKR2Cre-marked sensory neurons failed to activate hindbrain vagal efferent neurons or to drive catecholamine release from adrenal glands. As a result, ES no longer suppressed systemic inflammation induced by bacterial endotoxins. By contrast, spinal sympathetic reflexes evoked by high-intensity ES at both ST25 and ST36 sites were unaffected. We also show that optogenetic stimulation of PROKR2Cre-marked nerve terminals through the ST36 site is sufficient to drive the vagal-adrenal axis but not sympathetic reflexes. Furthermore, the distribution patterns of PROKR2Cre nerve fibres can retrospectively predict body regions at which low-intensity ES will or will not effectively produce anti-inflammatory effects. Our studies provide a neuroanatomical basis for the selectivity and specificity of acupoints in driving specific autonomic pathways.

Somato-Autonomic Reflexes of Acupuncture.

Objective: Acupuncture, as an important part of Traditional Chinese Medicine, has been practiced for thousands of years in China and now all over the world, but the underlying neuroanatomical basis is still poorly understood. This article explores how acupuncture drives autonomic reflexes and why the widely used Streitberger sham-needling control should be revisited. Method: This article summarizes modern studies, suggesting that functional connections between somatic tissues and internal organs may be explained via somato-autonomic reflexes. Results: Modern studies have revealed a few organizational rules regarding how acupuncture drives distinct somatosensory autonomic pathways, including acupoint selectivity and intensity dependence. Activation of these autonomic pathways modulates various body physiologic functions, such as gastrointestinal motility and systemic inflammation. Meanwhile, extensive anatomical and functional characterization of the somatosensory system raises a question about the widely used Streitberger sham-needling control. Specifically, the skin epidermis and hair follicles contain mechanically sensitive afferents, whose activation by this sham stimulation could modulate pain and the autonomic nervous system. Conclusions: A deeper understanding of the underlying neuroanatomical basis of acupuncture is crucial for optimizing stimulation parameters and designing proper sham-controls to demonstrate and improve the efficacy and the safety of using this modality to treat human conditions.

Somatotopic Organization and Intensity Dependence in Driving Distinct NPY-Expressing Sympathetic Pathways by Electroacupuncture.

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.

Mouse brain organization revealed through direct genome-scale TF expression analysis.

In the developing brain, transcription factors (TFs) direct the formation of a diverse array of neurons and glia. We identifed 1445 putative TFs in the mouse genome. We used in situ hybridization to map the expression of over 1000 of these TFs and TF-coregulator genes in the brains of developing mice. We found that 349 of these genes showed restricted expression patterns that were adequate to describe the anatomical organization of the brain. We provide a comprehensive inventory of murine TFs and their expression patterns in a searchable brain atlas database.