Resiliency to stress is crucial to the health of individuals and of society. While the detrimental effects of
prolonged stress are well-documented, there remains a critical knowledge gap regarding the mechanisms
underlying individual resilience to adverse outcomes. The circuits underlying stress resiliency, and how
resilient individuals tap into these circuits to maintain normal behavioral function, are not fully understood.
Furthermore, resiliency occurs over both long and short timescales and likely emerges from interactions
across neural subsystems that span molecules to whole-brain connectivity. To unravel these complex
mechanisms, we will use a multidisciplinary approach that combines time course experiments, machine
learning, signal processing, and statistical inference to integrate multidimensional data from the
transcriptome to the whole-brain connectome to characterize how circuit activity gives rise to resiliency.
We will collect behavioral, neuroimaging, electrophysiological, gene expression, and biomarker data from
well-validated mouse models of resilience. We will also develop new computational tools to characterize
the multiscale network dynamics of genes, molecules, and circuits that underlie the neurobiological
substrates of resilience. We will validate these relationships in another mouse strain to determine the
specificity of our model. This will be the first study to provide a comprehensive understanding of
interactions between neural circuits and their molecular, genomic, and neuroanatomical contexts in animal
models of resilience. If successful, our findings could yield insights into unifying principles of how neural
mechanisms interact to generate behavioral phenotypes.