In:
The Journal of Immunology, The American Association of Immunologists, Vol. 200, No. 1_Supplement ( 2018-05-01), p. 170.11-170.11
Abstract:
The autonomic nervous system regulates organ homeostasis via neural reflex circuits. The inflammatory reflex is the prototypical neural circuit composed of afferent and efferent fibers that travel via the vagus nerve to regulate TNF production. Previous studies have demonstrated that stimulation of the cervical vagus nerve attenuates serum TNF levels and cytokine production in the spleen, but efferent vagus nerve neurons originate both in the dorsal motor nucleus of the vagus (DMV) and in the nucleus ambiguus (NA) in the brainstem. The origin of the specific fibers that regulate splenic TNF production was previously unknown. Here, we selectively stimulated cholinergic neurons in the DMV and measured TNF in endotoxemic mice. A fiber-optic cannula was inserted under stereotactic guidance into the DMV in transgenic mice expressing channelrhodopsin under the choline acetyltransferase promoter. Animals were subjected to either optogenetic stimulation (n=15) or no light (sham control, n=15) for five minutes (473nm laser, 20Hz, 25% duty cycle). After 24 hours, animals were challenged with intraperitoneal lipopolysaccharide (0.25mg/kg), and serum collected after 90 min. Optogenetic stimulation but not sham stimulation of the cholinergic neurons in the DMV significantly attenuated endotoxin-induced serum TNF levels. Additionally, direct neural recording of splenic nerve activity during optogenetic stimulation of the DMV revealed that signals originating in the brainstem travel via the vagus nerve to the spleen. Together these studies provide new insights into the identity and central origin of the efferent vagus nerve fibers regulating TNF production during endotoxemia.
Type of Medium:
Online Resource
ISSN:
0022-1767
,
1550-6606
DOI:
10.4049/jimmunol.200.Supp.170.11
Language:
English
Publisher:
The American Association of Immunologists
Publication Date:
2018
detail.hit.zdb_id:
1475085-5
Permalink
