# Multiscale connectomic principles of resilience and susceptibility in mouse

> **NIH NIH R01** · COLUMBIA UNIVERSITY HEALTH SCIENCES · 2021 · $323,500

## Abstract

ABSTRACT
Like humans, mice subjected to stress can be divided into two phenotypes. Susceptible animals succumb to
maladaptive symptoms such as anhedonia and social avoidance, while resilient animals continue to behave
indistinguishably from controls. The mechanisms that drive this divergent stress-response remain elusive.
Understanding the functional relationship between individual variability in functional and structural connectivity
and stress-response is a critical first step in early identification of at-risk individuals and preventative
approaches that actively enhance resilience. We will address this relationship at multiple scales of resolution:
the whole-brain functional connectivity level using cFos co-activation mapping, the mesoscale structural
connectome level using viral-mediated trans-synaptic tracing, the synaptic level using single-cell 3D
reconstruction of dendritic spines, and the circuit level using viral-mediated identification and chemogenetic
control of a corticolimbic pathway. Multiscale circuits will be studied using a “time-course” approach, which will
provide mechanistic insight into how the functional and structural wiring diagram prior to a stressor contributes
to the development of divergent stress-responses. Our behavioral toolbox includes acute and chronic social
defeat stress resulting in subpopulations of resilient and susceptible mice, and novel non-stressful predictors of
each phenotype. In our preliminary studies, the basolateral amygdala (BLA) and its input from the prelimbic
cortex (PL), two regions involved in emotional regulation, have emerged as key players mediating divergent
stress-responses. In Aim 1, we will define the contribution of individual variability in BLA connectivity prior to
stress-exposure to BLA functional and structural reorganization during acute stress. In Aim 2, we will assess if
individual variability in functional and structural BLA connectivity becomes exacerbated following chronic
stress. In Aim 3, we will test the hypothesis that circuit rewiring prior to stress-exposure can alter future stress-
responses.

## Key facts

- **NIH application ID:** 10233812
- **Project number:** 5R01MH111918-06
- **Recipient organization:** COLUMBIA UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** DANI DUMITRIU
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $323,500
- **Award type:** 5
- **Project period:** 2018-12-05 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10233812

## Citation

> US National Institutes of Health, RePORTER application 10233812, Multiscale connectomic principles of resilience and susceptibility in mouse (5R01MH111918-06). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10233812. Licensed CC0.

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