An atlas of brain-bone sympathetic neural circuits in mice
- Icahn School of Medicine at Mount Sinai, United States
Abstract
There is clear evidence that the sympathetic nervous system (SNS) mediates bone metabolism. Histological studies show abundant SNS innervation of the periosteum and bone marrow-these nerves consist of noradrenergic fibers that immunostain for tyrosine hydroxylase, dopamine beta hydroxylase, or neuropeptide Y. Nonetheless, the brain sites that send efferent SNS outflow to bone have not yet been characterized. Using pseudorabies (PRV) viral transneuronal tracing, we report, for the first time, the identification of central SNS outflow sites that innervate bone. We find that the central SNS outflow to bone originates from 87 brain nuclei, sub-nuclei and regions of six brain divisions, namely the midbrain and pons, hypothalamus, hindbrain medulla, forebrain, cerebral cortex, and thalamus. We also find that certain sites, such as the raphe magnus (RMg) of the medulla and periaqueductal gray (PAG) of the midbrain, display greater degrees of PRV152 infection, suggesting that there is considerable site-specific variation in the levels of central SNS outflow to bone. This comprehensive compendium illustrating the central coding and control of SNS efferent signals to bone should allow for a greater understanding of the neural regulation of bone metabolism, and importantly and of clinical relevance, mechanisms for central bone pain.
Data availability
Figure 2-source data 1 contains the numerical data used to generate the figures.
Article and author information
Author details
Funding
National Institute on Aging (R01 AG071870)
- Se-Min Kim
- Tony Yuen
- Mone Zaidi
National Institute on Aging (U01 AG073148)
- Tony Yuen
- Mone Zaidi
National Institute on Aging (R01 AG074092)
- Tony Yuen
- Mone Zaidi
National Institute on Aging (U19 AG060917)
- Mone Zaidi
National Institute of Diabetes and Digestive and Kidney Diseases (R01 DK107670)
- Tony Yuen
- Mone Zaidi
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: All procedures were approved by the Mount Sinai Institutional Animal Care and Use Committee and were performed in accordance with Public Health Service and United States Department of Agriculture guidelines (IBC: SPROTO202200000224; IACUC: PROTO202100074).
Copyright
© 2024, Ryu et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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An atlas of brain-bone sympathetic neural circuits in mice
eLife 13:e95727.
https://doi.org/10.7554/eLife.95727
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