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The mouse brain after foot shock in four dimensions: Temporal dynamics at a single-cell resolution
Valeria Bonapersona1, Heike Schuler2,3, Ruth Damsteegt2
1Department of Translational Neuroscience, University Medical Center Utrecht Brain Center, Utrecht University, Utrecht 3584 CG, The Netherlands; v.bonapersona-2@umcutrecht.nl.
Acute stress rapidly activates most brain areas, with hypothalamic regions showing the earliest and most significant cellular activity changes. This study maps immediate early gene expression across the whole brain at single-cell resolution over time.
Area of Science:
- Neuroscience
- Systems Neuroscience
- Cellular Neuroscience
Background:
- Acute stress triggers sequential activation of functional brain networks.
- Identifying specific cells and their activity changes across the brain after stress is crucial.
Purpose of the Study:
- To develop a pipeline for charting whole-brain immediate early gene (IEG) expression as a proxy for cellular activity.
- To analyze IEG expression in four dimensions: functional networks, 3D space, single-cell resolution, and time.
- To map cellular activity changes across all brain areas following acute stress.
Main Methods:
- Developed a preprocessing and analytical pipeline for whole-brain IEG expression analysis.
- Utilized c-fos expression as a marker for cellular activity after a single foot shock.
- Analyzed data in four dimensions: functional networks, 3D, single-cell resolution, and time.
Main Results:
- 96% of brain areas showed increased c-fos+ cells post-stress.
- Hypothalamic areas exhibited the most active and prompt activation, followed by amygdala, prefrontal cortex, hippocampus, and thalamus.
- Cellular activity patterns (c-fos density and intensity) shifted over time and varied across brain areas, with some areas showing engram-like changes.
Conclusions:
- The developed pipeline enables comprehensive, high-resolution mapping of brain activity responses to acute stress.
- Stress-induced cellular activity is widespread but shows distinct temporal and spatial patterns across brain networks.
- The dynamic nature of cellular activity and potential engram formation highlight the brain's complex response to stress.
