1. Neuroscience

Multiple NTS neuron populations cumulatively suppress food intake

  1. Weiwei Qui
  2. Chelsea R Hutch
  3. Yi Wang
  4. Jennifer Wloszek
  5. Rachel A Rucker
  6. Martin G Myers Jr  Is a corresponding author
  7. Darleen Sandoval  Is a corresponding author
  1. University of Michigan-Ann Arbor, United States
  2. University of Colorado Anschutz Medical Campus, United States
https://doi.org/10.7554/eLife.85640
Share this article
Cite this article
  1. Weiwei Qui
  2. Chelsea R Hutch
  3. Yi Wang
  4. Jennifer Wloszek
  5. Rachel A Rucker
  6. Martin G Myers Jr
  7. Darleen Sandoval
(2023)
Multiple NTS neuron populations cumulatively suppress food intake
eLife 12:e85640.
https://doi.org/10.7554/eLife.85640
  2. Download BibTeX
  3. Download .RIS

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

  1. Weiwei Qui

    Department of Internal Medicine, University of Michigan-Ann Arbor, Ann Arbor, United States
    Competing interests
    No competing interests declared.

  2. Chelsea R Hutch

    Department of Surgery, University of Michigan-Ann Arbor, Ann Arbor, United States
    Competing interests
    No competing interests declared.

  3. Yi Wang

    Department of Internal Medicine, University of Michigan-Ann Arbor, Ann Arbor, United States
    Competing interests
    No competing interests declared.

  4. Jennifer Wloszek

    Department of Molecular and Integrative Physiology, University of Michigan-Ann Arbor, Ann Arbor, United States
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-4914-8877

  5. Rachel A Rucker

    Neuroscience Graduate Program, University of Michigan-Ann Arbor, Ann Arbor, United States
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-1434-9401

  6. Martin G Myers Jr

    Department of Internal Medicine, University of Michigan-Ann Arbor, Ann Arbor, United States
    For correspondence
    mgmyers@umich.edu
    Competing interests
    Martin G Myers, receives research support from AstraZeneca and Novo Nordisk..
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-9468-2046

  7. Darleen Sandoval

    Department of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora, United States
    For correspondence
    darleen.sandoval@cuanschutz.edu
    Competing interests
    Darleen Sandoval, is a consultant for Metis Therapeutics. The author declares that they have no other conflicts of interest.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-3669-3278

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.

Reviewing Editor

  1. Yunlei Yang, Albert Einstein College of Medicine, United States

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.

Version history

  1. Received: December 16, 2022
  2. Preprint posted: December 23, 2022 (view preprint)
  3. Accepted: December 5, 2023
  4. Accepted Manuscript published: December 7, 2023 (version 1)
  5. Accepted Manuscript updated: December 18, 2023 (version 2)
  6. Version of Record published: January 10, 2024 (version 3)

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.

Metrics

  • 801
    views
  • 180
    downloads
  • 1
    citations

Views, downloads and citations are aggregated across all versions of this paper published by eLife.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

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)

  1. Weiwei Qui
  2. Chelsea R Hutch
  3. Yi Wang
  4. Jennifer Wloszek
  5. Rachel A Rucker
  6. Martin G Myers Jr
  7. Darleen Sandoval
(2023)
Multiple NTS neuron populations cumulatively suppress food intake
eLife 12:e85640.
https://doi.org/10.7554/eLife.85640

Share this article

https://doi.org/10.7554/eLife.85640

Categories and tags

Research organism

Further reading

    1. Neuroscience

    Emergence of brain-like mirror-symmetric viewpoint tuning in convolutional neural networks

    Amirhossein Farzmahdi, Wilbert Zarco ... Tal Golan
    Research Article Updated

    Primates can recognize objects despite 3D geometric variations such as in-depth rotations. The computational mechanisms that give rise to such invariances are yet to be fully understood. A curious case of partial invariance occurs in the macaque face-patch AL and in fully connected layers of deep convolutional networks in which neurons respond similarly to mirror-symmetric views (e.g. left and right profiles). Why does this tuning develop? Here, we propose a simple learning-driven explanation for mirror-symmetric viewpoint tuning. We show that mirror-symmetric viewpoint tuning for faces emerges in the fully connected layers of convolutional deep neural networks trained on object recognition tasks, even when the training dataset does not include faces. First, using 3D objects rendered from multiple views as test stimuli, we demonstrate that mirror-symmetric viewpoint tuning in convolutional neural network models is not unique to faces: it emerges for multiple object categories with bilateral symmetry. Second, we show why this invariance emerges in the models. Learning to discriminate among bilaterally symmetric object categories induces reflection-equivariant intermediate representations. AL-like mirror-symmetric tuning is achieved when such equivariant responses are spatially pooled by downstream units with sufficiently large receptive fields. These results explain how mirror-symmetric viewpoint tuning can emerge in neural networks, providing a theory of how they might emerge in the primate brain. Our theory predicts that mirror-symmetric viewpoint tuning can emerge as a consequence of exposure to bilaterally symmetric objects beyond the category of faces, and that it can generalize beyond previously experienced object categories.

    1. Neuroscience

    Genetically defined nucleus incertus neurons differ in connectivity and function

    Emma D Spikol, Ji Cheng ... Marnie E Halpern
    Research Article

    The nucleus incertus (NI), a conserved hindbrain structure implicated in the stress response, arousal, and memory, is a major site for production of the neuropeptide relaxin-3. On the basis of goosecoid homeobox 2 (gsc2) expression, we identified a neuronal cluster that lies adjacent to relaxin 3a (rln3a) neurons in the zebrafish analogue of the NI. To delineate the characteristics of the gsc2 and rln3a NI neurons, we used CRISPR/Cas9 targeted integration to drive gene expression specifically in each neuronal group, and found that they differ in their efferent and afferent connectivity, spontaneous activity, and functional properties. gsc2 and rln3a NI neurons have widely divergent projection patterns and innervate distinct subregions of the midbrain interpeduncular nucleus (IPN). Whereas gsc2 neurons are activated more robustly by electric shock, rln3a neurons exhibit spontaneous fluctuations in calcium signaling and regulate locomotor activity. Our findings define heterogeneous neurons in the NI and provide new tools to probe its diverse functions.

    1. Neuroscience

    Visual working memories are abstractions of percepts

    Ziyi Duan, Clayton E Curtis
    Research Article

    During perception, decoding the orientation of gratings depends on complex interactions between the orientation of the grating, aperture edges, and topographic structure of the visual map. Here, we aimed to test how aperture biases described during perception affect working memory (WM) decoding. For memoranda, we used gratings multiplied by radial and angular modulators to generate orthogonal aperture biases for identical orientations. Therefore, if WM representations are simply maintained sensory representations, they would have similar aperture biases. If they are abstractions of sensory features, they would be unbiased and the modulator would have no effect on orientation decoding. Neural patterns of delay period activity while maintaining the orientation of gratings with one modulator (e.g. radial) were interchangeable with patterns while maintaining gratings with the other modulator (e.g. angular) in visual and parietal cortex, suggesting that WM representations are insensitive to aperture biases during perception. Then, we visualized memory abstractions of stimuli using models of visual field map properties. Regardless of aperture biases, WM representations of both modulated gratings were recoded into a single oriented line. These results provide strong evidence that visual WM representations are abstractions of percepts, immune to perceptual aperture biases, and compel revisions of WM theory.