The nucleus accumbens shell regulates hedonic feeding via a rostral hotspot.
Overview
- Department of Health Sciences and Technology, ETH Zurich, Zurich, Switzerland
- Functional Genomics Center Zurich, University of Zurich/ETH Zurich, Zurich, Switzerland
- Institute of Veterinary Physiology, University of Zurich – Vetsuisse, Zurich, Switzerland
- ETH Phenomics Center, ETH Zurich, Zurich, Switzerland
- Neuroscience Center Zurich, University and ETH Zurich, Zurich, Switzerland
Abstract
The medial nucleus accumbens shell (medNAcSh) is a key regulator of hedonic feeding, controlling reward consumption through its projections to downstream structures. Recent studies showed that the primary cellular mediators of these effects are dopamine 1 receptor-positive striatal projection neurons (D1-SPNs). Specifically, D1-SPN activity gets inhibited during reward consumption, and such inhibition is necessary and sufficient to authorize consumption, independent of metabolic need. Anatomically, the medNAcSh spans 1–1.5 mm along the rostro-caudal axis in mice, and previous studies have reported functional gradients along this axis. For instance, pharmacological studies have suggested that rostral rather than caudal medNAcSh regulates appetitive behavior. However, the mechanisms underlying this topographical gradient remain unknown. Here, we hypothesized that D1-SPNs contribute to this gradient by regulating hedonic feeding via a specific hotspot in the rostral medNAcSh. Using calcium monitoring with fiber photometry in mice, we show that rostral medNAcSh D1-SPNs demonstrate inhibitory responses during reward consumption, while caudal D1-SPNs do not. Consistently, optogenetic stimulation of rostral D1-SPNs inhibits consumption, while stimulation of caudal D1-SPNs had minimal effects, confirming the existence of a functional rostro-caudal gradient. Importantly, we observed no differences between rostral and caudal D1-SPNs in their responses to aversive stimuli, suggesting that the D1-SPN gradient is specific to appetitive contexts. To investigate potential molecular correlates of this functional gradient, we leveraged open-source anatomy datasets and performed fluorescent in situ hybridization, identifying Stard5 and Peg10 as markers enriched in the rostral and caudal medNAcSh, respectively. Finally, we developed a novel Stard5-Flp driver line to selectively target the rostral hotspot and demonstrated that Stard5+ neurons recapitulate rostral D1-SPN activity patterns. Together, these findings establish a spatially confined rostral medNAcSh subregion as a critical regulator of reward consumption and introduce Stard5 as a molecular tool for its manipulation, offering new opportunities for intervention in dysregulated eating.
Reproduced under the paper's license (CC BY), from the paper cited above.
Code
The paper links to its data, not to its authors' code: see the Data section.
Code availability
Original Python code to drive Pynapse is provided in Supplementary file 2. Please cite this paper upon usage of the code. No new MATLAB code was developed but the original code can be found in Labouesse et al., 2024; Labouesse et al., 2023.
Reproduced under the paper's license (CC BY), from the paper cited above.
Tracing map
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Data
Datasets cited
- geo:GSE118020, at NCBI GEO; found in the text, “Molecular rostro-caudal gradients across the…”
- zenodo:3925917, at Zenodo; found in the acknowledgements
- zenodo:5496332, at Zenodo; found in the acknowledgements
- zenodo:8319097, at Zenodo; found in the acknowledgements
Other data links
- ncbi.nlm.nih.gov/
bioproject , NCBI; found in the references
Data availability
Source data is provided as Source data 1.
Reproduced under the paper's license (CC BY), from the paper cited above.
Versions
The history of this record: each version stored by the harvester or made by a correction of its authors or of the maintainers of its code, and what changed in its facts. The texts of the paper (its abstract, its availability statements) are not part of it; versions that changed only those are not listed.
Version 1, 28 September 2026: the first record
Recorded: type, language, journal, volume, pages, dates, 8 authors, 1 keyword, 9 MeSH terms, 4 funders, 81 references, 4 RRIDs.
Cite
This paper
Marinescu, A.-M., Kamal, E., Leary, P., Navarro I Batista, K., Klug, M., Savić, N., Le Foll, C., & Labouesse, M. A. (2026). The nucleus accumbens shell regulates hedonic feeding via a rostral hotspot. eLife, 14, RP108639. https://
BibTeX
@article{marinescu2026nu
author = {Marinescu, Alina-Măriuca and Kamal, Eshita and Leary, Peter and Navarro I Batista, Keila and Klug, Manuel and Savić, Nataša and Le Foll, Christelle and Labouesse, Marie A},
title = {{The nucleus accumbens shell regulates hedonic feeding via a rostral hotspot}},
journal = {eLife},
year = {2026},
month = may,
volume = {14},
pages = {RP108639},
publisher = {eLife Sciences Publications, Ltd},
issn = {2050-084X},
doi = {10.7554/
url = {https://
pmid = {42165314},
pmcid = {PMC13193714}
}
RIS
TY - JOUR
AU - Marinescu, Alina-Măriuca
AU - Kamal, Eshita
AU - Leary, Peter
AU - Navarro I Batista, Keila
AU - Klug, Manuel
AU - Savić, Nataša
AU - Le Foll, Christelle
AU - Labouesse, Marie A
TI - The nucleus accumbens shell regulates hedonic feeding via a rostral hotspot
T2 - eLife
J2 - eLife
PY - 2026
DA - 2026/
VL - 14
SP - RP108639
SN - 2050-084X
PB - eLife Sciences Publications, Ltd
DO - 10.7554/
UR - https://
LA - en
ER -
CSL-JSON
{
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"container-title": "eLife",
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"family": "Marinescu",
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