Multiple NTS neuron populations cumulatively suppress food intake
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, Qiu 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.
Metrics
-
- 1,564
- views
-
- 270
- downloads
-
- 15
- citations
Views, downloads and citations are aggregated across all versions of this paper published by eLife.
Download links
Downloads (link to download the article as PDF)
Open citations (links to open the citations from this article in various online reference manager services)
Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)
Further reading
-
- Neuroscience
Synaptic inhibition is the mechanistic backbone of a suite of cortical functions, not the least of which are maintaining network stability and modulating neuronal gain. In cortical models with a single inhibitory neuron class, network stabilization and gain control work in opposition to one another – meaning high gain coincides with low stability and vice versa. It is now clear that cortical inhibition is diverse, with molecularly distinguished cell classes having distinct positions within the cortical circuit. We analyze circuit models with pyramidal neurons (E) as well as parvalbumin (PV) and somatostatin (SOM) expressing interneurons. We show how, in E – PV – SOM recurrently connected networks, SOM-mediated modulation can lead to simultaneous increases in neuronal gain and network stability. Our work exposes how the impact of a modulation mediated by SOM neurons depends critically on circuit connectivity and the network state.
-
- Neuroscience
The hippocampus is believed to encode episodic memory by binding information about the content of experience within a spatiotemporal framework encoding the location and temporal context of that experience. Previous work implies a distinction between positional inputs to the hippocampus from upstream brain regions that provide information about an animal’s location and nonpositional inputs which provide information about the content of experience, both sensory and navigational. Here, we leverage the phenomenon of ‘place field repetition’ to better understand the functional dissociation between positional and nonpositional information encoded in CA1. Rats navigated freely on a novel maze consisting of linear segments arranged in a rectilinear, city-block configuration, which combined elements of open-field foraging and linear-track tasks. Unlike typical results in open-field foraging, place fields were directionally tuned on the maze, even though the animal’s behavior was not constrained to extended, one-dimensional (1D) trajectories. Repeating fields from the same cell tended to have the same directional preference when the fields were aligned along a linear corridor of the maze, but they showed uncorrelated directional preferences when they were unaligned across different corridors. Lastly, individual fields displayed complex time dynamics which resulted in the population activity changing gradually over the course of minutes. These temporal dynamics were evident across repeating fields of the same cell. These results demonstrate that the positional inputs that drive a cell to fire in similar locations across the maze can be behaviorally and temporally dissociated from the nonpositional inputs that alter the firing rates of the cell within its place fields, offering a potential mechanism to increase the flexibility of the system to encode episodic variables within a spatiotemporal framework provided by place cells.