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Peer-reviewedCC BY-NC-NDThe Journal of Comparative Neurology

Mu Opioid Receptor mRNA and Protein Localization Across the Rat and Mouse Habenula

  • Alpa Popat1,2
  • Rhiana C. Simon3,1,4
  • Beatriz B. Aoyama1,5
  • Ahana Wokhlu1,4
  • Aliza T. Ehrlich6,7
  • Corey C. Harwell8,3,1,4
  • Elyssa B. Margolis8,1,4
8 affiliations
  1. 1UCSF Weill Institute for Neurosciences Department of Neurology University of California San Francisco California USA
  2. 2UCSF Weill Institute or Neurosciences, Department of Neurology, University of California, San Francisco, CA, USA
  3. 3The Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research San Francisco California USA
  4. 4UCSF Weill Institute for Neurosciences, Department of Neurology, University of California, San Francisco, CA, USA
  5. 5UCSF Weill Institute of Neurosciences, Department of Neurology, University of California, San Francisco, CA, USA
  6. 6UCSF Department of Psychiatry and Behavioral Sciences University of California San Francisco California USA
  7. 7UCSF Department of Psychiatry and Behavioral Sciences, University of California, San Francisco, CA, USA
  8. 8Neuroscience Graduate Program University of California San Francisco California USA
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Abstract

The habenula (Hb) has high‐intensity mu opioid binding and receptor (MOR) expression. It contains medial and lateral subdivisions (MHb and LHb, respectively), yet the details of MOR localization across these regions remain debated. MHb and LHb participate in largely non‐overlapping neural circuits; therefore, accurately resolving MOR expression across them is critical for understanding how MOR ligands impact behaviors. Here we utilized in situ hybridization (ISH) and immunocytochemistry (ICC) to systematically map Oprm1 mRNA and MOR protein throughout the habenular complex. We studied rat and mouse tissue to evaluate expression across two common research species. We also performed parallel mapping in Oprm1‐ Venus/Venus mice. Importantly, we found mRNA and protein in both MHb and LHb in both species. In rat, 39 ± 3% and 21 ± 4% of cells expressed Oprm1 in MHb and LHb, respectively. These proportions were greater in mouse: 57 ± 1% (MHb) and 32 ± 4% (LHb). Oprm1 puncta per positive cell were greater in MHb compared to LHb for both rat and mouse ( p < 0.0001). The highest intensity labeling was localized along the lateral edge of the MHb for all methods. ICC showed MOR localized to fibers and somata in both regions. In LHb, MOR labeling was most dense in intermediate sections along the anterior‐posterior (AP) axis. In rats we also observed greater labeling in dorsal LHb at intermediate AP levels and medial LHb more posteriorly. These results indicate that both MHb and LHb can contribute to MOR‐mediated actions through their respective circuits.

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Cite

BibTeXRIS
BibTeX
@article{popat2026opioid,
  title = {{Mu Opioid Receptor mRNA and Protein Localization Across the Rat and Mouse Habenula}},
  author = {Alpa Popat and Rhiana C. Simon and Beatriz B. Aoyama and Ahana Wokhlu and Aliza T. Ehrlich and Corey C. Harwell and Elyssa B. Margolis},
  journal = {The Journal of Comparative Neurology},
  year = {2026},
  month = jun,
  doi = {10.1002/cne.70175},
  url = {https://doi.org/10.1002/cne.70175},
  note = {CC BY-NC-ND},
}
RIS
TY  - JOUR
TI  - Mu Opioid Receptor mRNA and Protein Localization Across the Rat and Mouse Habenula
AU  - Alpa Popat
AU  - Rhiana C. Simon
AU  - Beatriz B. Aoyama
AU  - Ahana Wokhlu
AU  - Aliza T. Ehrlich
AU  - Corey C. Harwell
AU  - Elyssa B. Margolis
PY  - 2026
DA  - 2026/06/01
JO  - The Journal of Comparative Neurology
DO  - 10.1002/cne.70175
UR  - https://doi.org/10.1002/cne.70175
AB  - The habenula (Hb) has high‐intensity mu opioid binding and receptor (MOR) expression. It contains medial and lateral subdivisions (MHb and LHb, respectively), yet the details of MOR localization across these regions remain debated. MHb and LHb participate in largely non‐overlapping neural circuits; therefore, accurately resolving MOR expression across them is critical for understanding how MOR ligands impact behaviors. Here we utilized in situ hybridization (ISH) and immunocytochemistry (ICC) to systematically map Oprm1 mRNA and MOR protein throughout the habenular complex. We studied rat and mouse tissue to evaluate expression across two common research species. We also performed parallel mapping in Oprm1‐ Venus/Venus mice. Importantly, we found mRNA and protein in both MHb and LHb in both species. In rat, 39 ± 3% and 21 ± 4% of cells expressed Oprm1 in MHb and LHb, respectively. These proportions were greater in mouse: 57 ± 1% (MHb) and 32 ± 4% (LHb). Oprm1 puncta per positive cell were greater in MHb compared to LHb for both rat and mouse ( p < 0.0001). The highest intensity labeling was localized along the lateral edge of the MHb for all methods. ICC showed MOR localized to fibers and somata in both regions. In LHb, MOR labeling was most dense in intermediate sections along the anterior‐posterior (AP) axis. In rats we also observed greater labeling in dorsal LHb at intermediate AP levels and medial LHb more posteriorly. These results indicate that both MHb and LHb can contribute to MOR‐mediated actions through their respective circuits.
SN  - 0021-9967
SN  - 0092-7317
SN  - 1096-9861
SN  - 1550-7130
ER  -