Molecular and spatial profiling of the paraventricular nucleus of the thalamus

  1. Claire Gao  Is a corresponding author
  2. Chiraag A Gohel
  3. Yan Leng
  4. Jun Ma
  5. David Goldman
  6. Ariel J Levine
  7. Mario A Penzo  Is a corresponding author
  1. National Institute of Mental Health, United States
  2. National Institute on Alcohol Abuse and Alcoholism, United States
  3. National Institute of Child Health and Human Development, United States

Abstract

The paraventricular nucleus of the thalamus (PVT) is known to regulate various cognitive and behavioral processes. However, while functional diversity among PVT circuits has often been linked to cellular differences, the molecular identity and spatial distribution of PVT cell types remains unclear. To address this gap, here we used single nucleus RNA sequencing (snRNA-seq) and identified five molecularly distinct PVT neuronal subtypes in the mouse brain. Additionally, multiplex fluorescent in situ hybridization of top marker genes revealed that PVT subtypes are organized by a combination of previously unidentified molecular gradients. Lastly, comparing our dataset with a recently published single-cell sequencing atlas of thalamus yielded novel insight into the PVT's connectivity with cortex, including unexpected innervation of auditory and visual areas. This comparison also revealed that our data contains a largely non-overlapping transcriptomic map of multiple midline thalamic nuclei. Collectively, our findings uncover previously unknown features of the molecular diversity and anatomical organization of the PVT and provide a valuable resource for future investigations.

Data availability

All RNA-seq data generated in our study have been deposited into the Gene Expression Omnibus repository (GSE208707). Raw images of RNAscope experiments are publicly available at: https://figshare.com/s/e2918829cabfdd0392fb.

The following data sets were generated
The following previously published data sets were used

Article and author information

Author details

  1. Claire Gao

    National Institute of Mental Health, Bethesda, United States
    For correspondence
    claire.gao@nih.gov
    Competing interests
    The authors declare that no competing interests exist.
  2. Chiraag A Gohel

    National Institute on Alcohol Abuse and Alcoholism, Bethesda, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Yan Leng

    National Institute of Mental Health, Bethesda, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Jun Ma

    National Institute of Mental Health, Bethesda, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. David Goldman

    National Institute on Alcohol Abuse and Alcoholism, Bethesda, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Ariel J Levine

    National Institute of Child Health and Human Development, Bethesda, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-0335-0730
  7. Mario A Penzo

    National Institute of Mental Health, Bethesda, United States
    For correspondence
    mario.penzo@nih.gov
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-5368-1802

Funding

National Institute of Mental Health (1ZIAMH002950)

  • Mario A Penzo

National Institute of Neurological Disorders and Stroke (ZIANS003153)

  • Ariel J Levine

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

Ethics

Animal experimentation: All procedures were performed in accordance with the Guide for the Care and Use of Laboratory Animals and were approved by the National Institute of Mental Health Animal Care and Use Committee. (See Methods - Mice)

Copyright

This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.

Metrics

  • 3,996
    views
  • 594
    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. Claire Gao
  2. Chiraag A Gohel
  3. Yan Leng
  4. Jun Ma
  5. David Goldman
  6. Ariel J Levine
  7. Mario A Penzo
(2023)
Molecular and spatial profiling of the paraventricular nucleus of the thalamus
eLife 12:e81818.
https://doi.org/10.7554/eLife.81818

Share this article

https://doi.org/10.7554/eLife.81818

Further reading

    1. Neuroscience
    William T Redman, Santiago Acosta-Mendoza ... Michael J Goard
    Research Article

    Although grid cells are one of the most well-studied functional classes of neurons in the mammalian brain, whether there is a single orientation and spacing value per grid module has not been carefully tested. We analyze a recent large-scale recording of medial entorhinal cortex to characterize the presence and degree of heterogeneity of grid properties within individual modules. We find evidence for small, but robust, variability and hypothesize that this property of the grid code could enhance the encoding of local spatial information. Performing analysis on synthetic populations of grid cells, where we have complete control over the amount heterogeneity in grid properties, we demonstrate that grid property variability of a similar magnitude to the analyzed data leads to significantly decreased decoding error. This holds even when restricted to activity from a single module. Our results highlight how the heterogeneity of the neural response properties may benefit coding and opens new directions for theoretical and experimental analysis of grid cells.

    1. Neuroscience
    Maren Klingelhöfer-Jens, Katharina Hutterer ... Tina B Lonsdorf
    Research Article

    Childhood adversity is a strong predictor of developing psychopathological conditions. Multiple theories on the mechanisms underlying this association have been suggested which, however, differ in the operationalization of ‘exposure.’ Altered (threat) learning mechanisms represent central mechanisms by which environmental inputs shape emotional and cognitive processes and ultimately behavior. 1402 healthy participants underwent a fear conditioning paradigm (acquisition training, generalization), while acquiring skin conductance responses (SCRs) and ratings (arousal, valence, and contingency). Childhood adversity was operationalized as (1) dichotomization, and following (2) the specificity model, (3) the cumulative risk model, and (4) the dimensional model. Individuals exposed to childhood adversity showed blunted physiological reactivity in SCRs, but not ratings, and reduced CS+/CS- discrimination during both phases, mainly driven by attenuated CS+ responding. The latter was evident across different operationalizations of ‘exposure’ following the different theories. None of the theories tested showed clear explanatory superiority. Notably, a remarkably different pattern of increased responding to the CS- is reported in the literature for anxiety patients, suggesting that individuals exposed to childhood adversity may represent a specific sub-sample. We highlight that theories linking childhood adversity to (vulnerability to) psychopathology need refinement.