# Role of basolateral amygdala projections in mediating individual differences in motivation and flexibility

> **NIH NIH R01** · UNIVERSITY OF MARYLAND BALTIMORE · 2022 · $386,250

## Abstract

PROJECT SUMMARY
While many individuals try drugs of abuse, only a subset transition to addiction. Studying individual differences
in addiction vulnerability is a critical step towards understanding the neurobiological underpinnings of
motivation for drugs and their impact on the brain and behavior. Nine of eleven of the DSMV criteria for
diagnosing individuals with substance use disorder relate to heightened motivation for drugs or behavioral
inflexibility, characterized by persistence to seek and take drugs despite negative consequences. The dual
nature of this psychological profile inspires this research program, which considers both motivation and
flexibility prior to drug experience in order to understand addiction vulnerability. Phenotypic behavioral
differences, termed sign-tracking and goal-tracking, differentially predict vulnerability to drug seeking. Sign-
and goal-tracking traits are observed in rodents and humans, and are a promising trait distinction for
characterizing addiction vulnerability across species. Sign-trackers show heightened motivation for food- and
drug-associated discrete cues compared to goal-trackers. Recent work from our laboratory shows that sign-
tracking rats are inflexible, continuing to respond to previously rewarded cues, even when the value of the
reward has been degraded. Taken together, the “tracking trait” distinction is an ideal model to explore
individual differences in both motivation and flexibility prior to drug experience. But what are the brain
mechanisms underlying these trait differences? The basolateral amygdala is a critical brain site for initial
encoding of cue value that is key for supporting both appetitive motivation and flexibility through its interactions
with downstream targets, the nucleus accumbens and insular cortex. We propose that individual differences in
appetitive motivation and behavioral flexibility of sign- and goal-trackers are mediated by distinct basolateral
amygdala projections to the nucleus accumbens and insular cortex. Here we use coordinated neurobiological
approaches to test specific predictions of our hypothesis. Frist, we examine whether neuronal activity in distinct
basolateral amygdala pathways supports appetitive motivation in sign- and goal-trackers. Next, we determine
whether these circuits are differentially engaged and critical for driving variations in flexible behavior of sign-
and goal-trackers when outcome value gets worse. Then, we determine the impact of disrupting basolateral
amygdala input on encoding in downstream nucleus accumbens and insular cortex during appetitive motivation
and modification of outcome value. Finally, we determine whether the basolateral amygdala pathway activated
during initial learning biases the individual towards an appetitive motivated or flexible behavioral strategy. We
make use of novel tools to be the first to investigate the role of specific basolateral amygdala pathways in
driving the distinct behavior of sign- and goal...

## Key facts

- **NIH application ID:** 10454867
- **Project number:** 5R01DA043533-06
- **Recipient organization:** UNIVERSITY OF MARYLAND BALTIMORE
- **Principal Investigator:** Donna Calu Gogerdchi
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $386,250
- **Award type:** 5
- **Project period:** 2017-09-01 → 2025-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10454867

## Citation

> US National Institutes of Health, RePORTER application 10454867, Role of basolateral amygdala projections in mediating individual differences in motivation and flexibility (5R01DA043533-06). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10454867. Licensed CC0.

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