Specialized neurons in the right habenula mediate response to aversive olfactory cues

  1. Jung-Hwa Choi
  2. Erik R Duboue
  3. Michelle Macurak
  4. Jean-Michel Chanchu
  5. Marnie E Halpern  Is a corresponding author
  1. Dartmouth College, United States
  2. Florida Atlantic University, United States
  3. Carnegie Institution for Science, United States

Abstract

Hemispheric specializations are well studied at the functional level but less is known about the underlying neural mechanisms. We identified a small cluster of cholinergic neurons in the dorsal habenula (dHb) of zebrafish, defined by their expression of the lecithin retinol acyltransferase domain containing 2a (lratd2a) gene and their efferent connections with a subregion of the ventral interpeduncular nucleus (vIPN). The lratd2a-expressing neurons in the right dHb are innervated by a subset of mitral cells from both the left and right olfactory bulb and are activated upon exposure to the odorant cadaverine that is repellent to adult zebrafish. Using an intersectional strategy to drive expression of the botulinum neurotoxin specifically in these neurons, we find that adults no longer show aversion to cadaverine. Mutants with left-isomerized dHb that lack these neurons are also less repelled by cadaverine and their behavioral response to alarm substance, a potent aversive cue, is diminished. However, mutants in which both dHb have right identity appear more reactive to alarm substance. The results implicate an asymmetric dHb-vIPN neural circuit in the processing of repulsive olfactory cues and in modulating the resultant behavioral response.

Data availability

All data generated or analyzed during this study are included in the manuscript and supporting file; Source Data files have been provided for Figures 1-5.Behavioral analyses were performed using custom written scripts in MATLAB and uploaded as Source Code Files.

Article and author information

Author details

  1. Jung-Hwa Choi

    Geisel School of Medicine at Dartmouth, Department of Molecular and Systems Biology, Dartmouth College, Hanover, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Erik R Duboue

    Harriet Wilkes Honors College, Florida Atlantic University, Jupiter, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-3303-5149
  3. Michelle Macurak

    Department of Embryology, Carnegie Institution for Science, Baltimore, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Jean-Michel Chanchu

    Department of Embryology, Carnegie Institution for Science, Baltimore, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Marnie E Halpern

    Geisel School of Medicine at Dartmouth, Department of Molecular and Systems Biology, Dartmouth College, Hanover, United States
    For correspondence
    Marnie.E.Halpern@Dartmouth.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-3634-9058

Funding

National Institutes of Health (R01HD078220)

  • Marnie E Halpern

National Institutes of Health (R37HD091280)

  • Marnie E Halpern

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Claire Wyart, Institut du Cerveau et la Moelle épinière, Hôpital Pitié-Salpêtrière, Sorbonne Universités, UPMC Univ Paris 06, Inserm, CNRS, France

Ethics

Animal experimentation: All zebrafish protocols were approved by the Institutional Animal Care and Use Committee (IACUC) of the Carnegie Institution for Science [Protocol #122] or Dartmouth College [Protocol #00002253(m3a)].

Version history

  1. Preprint posted: July 20, 2021 (view preprint)
  2. Received: July 20, 2021
  3. Accepted: December 7, 2021
  4. Accepted Manuscript published: December 8, 2021 (version 1)
  5. Version of Record published: December 21, 2021 (version 2)

Copyright

© 2021, Choi 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

  • 1,725
    views
  • 237
    downloads
  • 22
    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. Jung-Hwa Choi
  2. Erik R Duboue
  3. Michelle Macurak
  4. Jean-Michel Chanchu
  5. Marnie E Halpern
(2021)
Specialized neurons in the right habenula mediate response to aversive olfactory cues
eLife 10:e72345.
https://doi.org/10.7554/eLife.72345

Share this article

https://doi.org/10.7554/eLife.72345

Further reading

    1. Neuroscience
    Harshvardhan Gazula, Henry FJ Tregidgo ... Juan E Iglesias
    Tools and Resources

    We present open-source tools for three-dimensional (3D) analysis of photographs of dissected slices of human brains, which are routinely acquired in brain banks but seldom used for quantitative analysis. Our tools can: (1) 3D reconstruct a volume from the photographs and, optionally, a surface scan; and (2) produce a high-resolution 3D segmentation into 11 brain regions per hemisphere (22 in total), independently of the slice thickness. Our tools can be used as a substitute for ex vivo magnetic resonance imaging (MRI), which requires access to an MRI scanner, ex vivo scanning expertise, and considerable financial resources. We tested our tools on synthetic and real data from two NIH Alzheimer’s Disease Research Centers. The results show that our methodology yields accurate 3D reconstructions, segmentations, and volumetric measurements that are highly correlated to those from MRI. Our method also detects expected differences between post mortem confirmed Alzheimer’s disease cases and controls. The tools are available in our widespread neuroimaging suite ‘FreeSurfer’ (https://surfer.nmr.mgh.harvard.edu/fswiki/PhotoTools).

    1. Neuroscience
    John J Maurer, Alexandra Lin ... Shinjae Chung
    Research Article

    Rapid eye movement sleep (REMs) is characterized by activated electroencephalogram (EEG) and muscle atonia, accompanied by vivid dreams. REMs is homeostatically regulated, ensuring that any loss of REMs is compensated by a subsequent increase in its amount. However, the neural mechanisms underlying the homeostatic control of REMs are largely unknown. Here, we show that GABAergic neurons in the preoptic area of the hypothalamus projecting to the tuberomammillary nucleus (POAGAD2→TMN neurons) are crucial for the homeostatic regulation of REMs in mice. POAGAD2→TMN neurons are most active during REMs, and inhibiting them specifically decreases REMs. REMs restriction leads to an increased number and amplitude of calcium transients in POAGAD2→TMN neurons, reflecting the accumulation of REMs pressure. Inhibiting POAGAD2→TMN neurons during REMs restriction blocked the subsequent rebound of REMs. Our findings reveal a hypothalamic circuit whose activity mirrors the buildup of homeostatic REMs pressure during restriction and that is required for the ensuing rebound in REMs.