# Individual Differences in Epigenetic Regulation of Emotional Learning

> **NIH NIH R01** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2020 · $462,379

## Abstract

PROJECT SUMMARY/ABSTRACT
This research project focuses on identifying common neurobiological substrates that confer vulnerability both
to addiction and to frequently co-occurring disorders such as post-traumatic stress disorder (PTSD). Pavlovian
conditioning procedures will be used to distinguish “sign-tracking” rats that tend to attribute high levels of
motivational significance to discrete predictive cues while largely ignoring context, from “goal-tracking” rats that
make more use of context to appropriately modify their emotional responses. Sign-tracking individuals are
more prone to both addiction- and PTSD-like behaviors than goal-trackers. The neurobiological basis of these
behavioral traits will be explored by testing for differences between sign- and goal-trackers in dynamic
epigenetic histone acetylation, brain-derived neurotrophic factor (BDNF) expression, and functional
connectivity within key limbic circuits known to mediate motivated behavior, namely the pathway from ventral
hippocampus to medial prefrontal cortex to basolateral amygdala and nucleus accumbens. Epigenetic changes
and growth factor expression will also be manipulated using viral vectors to test for a causal influence on
conditioned motivational responses to appetitive and aversive cues and contexts, as well as
electrophysiological measures of connectivity and synaptic efficiency within the limbic pathway of interest.
These experiments will test the hypothesis that decreased histone acetylation in goal-trackers relative to sign-
trackers after behavioral conditioning leads to increased transcription of BDNF, which in turn is transported
axonally and released onto medial prefrontal cortical targets. The BDNF then causes an increase in synaptic
connectivity between the medial prefrontal cortex and its downstream targets, the basolateral amygdala and
nucleus accumbens. Thus, goal-trackers are hypothesized to have an increased capacity to use contextual
information, derived from hippocampal inputs and relayed through the medial prefrontal cortex, to appropriately
modify subcortical responses to cues associated with emotionally salient events. This proposed R01 project is
well-aligned with the missions of the NIH and NIDA, as it will help clarify neurobiological pathways to addiction
and frequently co-occurring disorders, which is a significant public health priority.

## Key facts

- **NIH application ID:** 9981714
- **Project number:** 5R01DA044960-03
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **Principal Investigator:** Jonathan David Morrow
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $462,379
- **Award type:** 5
- **Project period:** 2018-09-30 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9981714

## Citation

> US National Institutes of Health, RePORTER application 9981714, Individual Differences in Epigenetic Regulation of Emotional Learning (5R01DA044960-03). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/9981714. Licensed CC0.

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