# Integrated single cell and spatial mapping of habenula circuitry to identify projection-specific molecular pathways associated with opioid exposure.

> **NIH NIH R21** · LIEBER INSTITUTE, INC. · 2024 · $284,040

## Abstract

PROJECT SUMMARY
The national opioid epidemic is a significant public health crisis requiring accelerated efforts to translate
mechanistic studies into therapeutic developments. Substance use disorders (SUDs) feature dysregulation of
brain reward circuits, especially dopaminergic systems governing motivated behavior. The habenula (Hb) is a
key reward circuitry hub that sends direct projections to the ventral tegmental area (VTA), as well as other
aminergic centers, to modulate reward seeking. Hb circuit dysfunction is associated with addiction, but the
molecular mechanisms mediating this dysfunction, especially in the context of opioid use disorder (OUD) are
unknown. Here we propose to use integrated single cell and spatial transcriptomic approaches to map
molecular changes associated with chronic opioid self-administration in specific cell populations across the
rodent Hb (Aim 1). Using retrograde labeling and nuclear tagging, we will also generate transcriptomic
signatures for Hb neurons projecting to the VTA (Hb-VTA projections) and evaluate their susceptibility to
molecular changes associated with chronic opioid exposure (Aim 2). Finally, we will integrate these
complimentary rodent datasets with molecular data we are generating in the post-mortem human Hb in the
context of OUD as part of an ongoing NIDA-funded award (1R01DA55823) to identify specific Hb cell
populations and projection neurons enriched in genes associated with opioid addiction in the human brain (Aim
3). The proposed study will generate the first spatially-resolved atlas of opioid-induced gene expression
changes in the rodent Hb at cellular and circuit resolution. Integration of this molecular map with clinical gene
sets in the context of OUD will help translate insights from rodent models into cell type- and circuit-based
therapeutic approaches for the treatment of addiction.

## Key facts

- **NIH application ID:** 10877593
- **Project number:** 1R21DA060407-01
- **Recipient organization:** LIEBER INSTITUTE, INC.
- **Principal Investigator:** Kristen Rose Maynard
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $284,040
- **Award type:** 1
- **Project period:** 2024-09-01 → 2026-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10877593

## Citation

> US National Institutes of Health, RePORTER application 10877593, Integrated single cell and spatial mapping of habenula circuitry to identify projection-specific molecular pathways associated with opioid exposure. (1R21DA060407-01). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10877593. Licensed CC0.

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