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A SMARTTR workflow for multi-ensemble atlas mapping and brain-wide network analysis.

Michelle Jin1,2, Simon O Ogundare1,3, Marcos Lanio1,4

  • 1Medical Scientist Training Program (MSTP), Columbia University Irving Medical Center (CUIMC), New York, United States.

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|July 25, 2025
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Summary
This summary is machine-generated.

We developed a new workflow and R package (SMARTTR) for brain-wide mapping of multiple gene activity patterns. This tool reveals how inescapable shock alters brain networks in learned helplessness, impacting spatial and affective processing.

Keywords:
activity mappingcomputational biologyengramimmediate early genelearned helplessnessmousenetworkneurosciencesystems biology

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Area of Science:

  • Neuroscience
  • Computational Biology
  • Systems Neuroscience

Background:

  • Activity-dependent strategies have advanced understanding of memory.
  • Limited tools exist for brain-wide mapping of multiple neural ensembles and their overlaps.
  • Downstream network analysis capabilities are lacking in current methods.

Purpose of the Study:

  • To introduce a scalable workflow for analyzing multi-ensemble datasets from activity-dependent tagging systems.
  • To present SMARTTR, an R package for atlas registration, statistical analysis, and network visualization.
  • To demonstrate the workflow's utility in mapping neural ensembles related to learned helplessness.

Main Methods:

  • Developed a scalable workflow for analyzing coronally sectioned datasets.
  • Created the SMARTTR R package integrating mapping, statistical analysis, and network visualization.
  • Applied the workflow to map neural ensembles in a learned helplessness mouse model.

Main Results:

  • Inescapable shock (IS) decreased centrality of spatial/contextual regions and increased somatosensory/affective regions.
  • The substantia nigra became influential during learned helplessness expression, potentially regulating motor activity.
  • IS suppressed ensemble reactivation in cortical, hippocampal, and amygdalar regions, suggesting a neurobiological signature of learned helplessness.

Conclusions:

  • The SMARTTR workflow enables novel insights into multi-ensemble brain activity.
  • Network analysis reveals significant alterations in brain regions associated with learned helplessness.
  • Suppressed ensemble reactivation may be a key neurobiological feature of learned helplessness.