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PreprintCC BY-NC-NDbioRxiv

Anatomical mapping of dopamine D1 and muscarinic M4 receptor

  1. 1Northeastern University

Abstract

Dopamine D1 receptors (D1R) and muscarinic M4 receptors (M4R) regulate overlapping functions in the cortex and the striatum, but the cellular relationship between D1R- and M4R-associated populations across brain regions remains incompletely defined. Using D1R-tdTomato/M4R-EGFP double-reporter mice, we quantified tdTomato-only, EGFP-only, and coexpressing cellular populations across the dorsal striatum, nucleus accumbens, and medial prefrontal cortex in 18 animals. Reporter composition differed strongly by anatomical region. Coexpression was prominent throughout the dorsal striatum and greatest in the dorsomedial striatum, whereas the nucleus accumbens shifted toward greater tdTomato-only and reduced EGFP-only representation, particularly in the core. In contrast, the medial prefrontal cortex was dominated by EGFP-only cells. These regional patterns were broadly retained across sex and age. HCR-FISH further supported spatial correspondence between endogenous Drd1 and Chrm4 transcript signal and the respective fluorescent reporters. Together, these findings demonstrate region-dependent organization of D1R- and M4R-associated cellular populations across the cortex and striatum and define distinct anatomical contexts in which M4R-directed signaling may influence D1R-associated neurons.

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BibTeX
@misc{garland2026anatomical,
  title = {{Anatomical mapping of dopamine D1 and muscarinic M4 receptor}},
  author = {R. Garland and M. Dickson and A. Lee and A. Noorouzi and H. Umaoka and A. Semeano and J. R. Monaghan and H. Yano},
  howpublished = {bioRxiv},
  year = {2026},
  month = sep,
  doi = {10.64898/2026.09.27.754786},
  url = {https://www.biorxiv.org/content/10.64898/2026.09.27.754786v1},
  note = {CC BY-NC-ND},
}
RIS
TY  - UNPB
TI  - Anatomical mapping of dopamine D1 and muscarinic M4 receptor
AU  - R. Garland
AU  - M. Dickson
AU  - A. Lee
AU  - A. Noorouzi
AU  - H. Umaoka
AU  - A. Semeano
AU  - J. R. Monaghan
AU  - H. Yano
PY  - 2026
DA  - 2026/09/27
PB  - bioRxiv
DO  - 10.64898/2026.09.27.754786
UR  - https://www.biorxiv.org/content/10.64898/2026.09.27.754786v1
AB  - Dopamine D1 receptors (D1R) and muscarinic M4 receptors (M4R) regulate overlapping functions in the cortex and the striatum, but the cellular relationship between D1R- and M4R-associated populations across brain regions remains incompletely defined. Using D1R-tdTomato/M4R-EGFP double-reporter mice, we quantified tdTomato-only, EGFP-only, and coexpressing cellular populations across the dorsal striatum, nucleus accumbens, and medial prefrontal cortex in 18 animals. Reporter composition differed strongly by anatomical region. Coexpression was prominent throughout the dorsal striatum and greatest in the dorsomedial striatum, whereas the nucleus accumbens shifted toward greater tdTomato-only and reduced EGFP-only representation, particularly in the core. In contrast, the medial prefrontal cortex was dominated by EGFP-only cells. These regional patterns were broadly retained across sex and age. HCR-FISH further supported spatial correspondence between endogenous Drd1 and Chrm4 transcript signal and the respective fluorescent reporters. Together, these findings demonstrate region-dependent organization of D1R- and M4R-associated cellular populations across the cortex and striatum and define distinct anatomical contexts in which M4R-directed signaling may influence D1R-associated neurons.
ER  -