Multiple NTS neuron populations cumulatively suppress food intake
- University of Michigan-Ann Arbor, United States
- University of Colorado Anschutz Medical Campus, United States
Abstract
Several discrete groups of feeding-regulated neurons in the nucleus of the solitary tract (nucleus tractus solitarius; NTS) suppress food intake, including avoidance-promoting neurons that express Cck (NTSCck cells) and distinct Lepr- and Calcr-expressing neurons (NTSLepr and NTSCalcr cells, respectively) that suppress food intake without promoting avoidance. To test potential synergies among these cell groups we manipulated multiple NTS cell populations simultaneously. We found that activating multiple sets of NTS neurons (e.g., NTSLepr plus NTSCalcr (NTSLC), or NTSLC plus NTSCck (NTSLCK)) suppressed feeding more robustly than activating single populations. While activating groups of cells that include NTSCck neurons promoted conditioned taste avoidance (CTA), NTSLC activation produced no CTA despite abrogating feeding. Thus, the ability to promote CTA formation represents a dominant effect but activating multiple non-aversive populations augments the suppression of food intake without provoking avoidance. Furthermore, silencing multiple NTS neuron groups augmented food intake and body weight to a greater extent than silencing single populations, consistent with the notion that each of these NTS neuron populations plays crucial and cumulative roles in the control of energy balance. We found that silencing NTSLCK neurons failed to blunt the weight-loss response to vertical sleeve gastrectomy (VSG) and that feeding activated many non-NTSLCK neurons, however, suggesting that as-yet undefined NTS cell types must make additional contributions to the restraint of feeding.
Data availability
All data generated are included in the manuscript and supplemental figures
Article and author information
Author details
Funding
National Institute of Diabetes and Digestive and Kidney Diseases (P01 DK117821)
- Martin G Myers Jr
National Institute of Diabetes and Digestive and Kidney Diseases (P30 DK020572)
- Martin G Myers Jr
National Institute of Diabetes and Digestive and Kidney Diseases (P01 DK117821)
- Darleen Sandoval
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: Mice were bred in our colony in the Unit for Laboratory Animal Medicine at the University of Michigan; these mice and the procedures performed were approved by the University of Michigan Committee on the Use and Care of Animals (Protocol#00011066) and in accordance with Association for the Assessment and Approval of Laboratory Animal Care and National Institutes of Health guidelines. Mice were provided with food and water ad libitum (except as noted below) in temperature-controlled rooms on a 12-hour light-dark cycle. For all studies, animals were processed in the order of their ear tag number, which was randomly assigned at the time of tailing (before genotyping). ARRIVE guidelines were followed; animals were group-housed except for feeding and CTA studies. All surgery was performed under isoflurane anesthesia and every effort was made to minimize suffering.
Copyright
© 2023, Qui 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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Multiple NTS neuron populations cumulatively suppress food intake
eLife 12:e85640.
https://doi.org/10.7554/eLife.85640
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