Brain-wide mapping reveals temporal and sexually dimorphic opioid actions
Iaroslavna Vasylieva1,2, Reese Smith1,2, Eshan Aravind1,3
1Center for Biologic Imaging, University of Pittsburgh, Pittsburgh, PA, USA.
Communications Biology
|February 20, 2026
Summary
Researchers developed a scalable computational workflow to map neuronal activity in whole brains, revealing distinct sex-based responses to morphine and supporting the multi-wave model of opioid brain activation.
Area of Science:
- Neuroscience
- Computational Biology
- Neuroimaging
Background:
- Spatial mapping of neuronal activity in whole cleared brains is revolutionizing neuroscience.
- Efficient computational workflows are crucial for analyzing large-scale, multi-condition experiments.
Purpose of the Study:
- To develop a scalable computational workflow for anatomical mapping of c-Fos positive cells in whole brains.
- To investigate the spatiotemporal patterns of brain activation induced by morphine, considering sex differences.
Main Methods:
- Developed a scalable computational approach for whole-brain c-Fos cell mapping.
- Applied the workflow to analyze brain activation patterns following acute morphine administration in mice.
- Quantified c-Fos expression to identify regions with altered neuronal activity.
Main Results:
- Identified distinct patterns of morphine-induced regional brain activation that vary across time and sex.
- Observed significantly higher c-Fos expression in males compared to females in key reward and emotional processing regions.
- Results support the multi-wave model of opioid-induced brain activation.
Conclusions:
- The developed workflow enables scalable, whole-brain analysis of neuronal activity.
- Morphine elicits complex, sex-specific spatiotemporal brain activation patterns.
- This approach is broadly applicable for studying drugs of abuse and general neuronal mapping.
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