# Probing the role of a hypothalamic-thalamic-striatal circuit in cue-driven behaviors

> **NIH NIH R01** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2024 · $41,055

## Abstract

PROJECT SUMMARY/ABSTRACT
Stimuli (cues) in the environment associated with reward can motivate normal behavior, bringing one in close
proximity to valuable resources (e.g. food); but they can also gain inordinate control over behavior, as is the
case with addiction. The ability of reward cues to motivate behavior occurs through Pavlovian learning
processes. When a discrete cue is repeatedly paired with presentation of a reward, it can acquire the ability to
act as a predictor, but can also acquire incentive motivational properties. In individuals with addiction, cues that
have been previously associated with the drug-taking experience acquire the ability to maintain drug-seeking
behavior and instigate relapse, even when there is a strong desire to stop use. The neurobiological processes
by which reward cues gain inordinate control over behavior have proven difficult to discern because cues can
simultaneously acquire “predictive” and “incentive” properties, and in most studies these two psychological
processes are confounded. In the proposed studies we will exploit natural variation in cue-reward learning to
identify the neural circuitry specifically responsible for the attribution of incentive motivational value (incentive
salience) to reward cues. When rats are exposed to a Pavlovian conditioned approach paradigm, some,
termed “goal-trackers”, attribute predictive value to a discrete food-associated cue; whereas others, termed
“sign-trackers” attribute incentive salience to the cue. Relative to goal-trackers, sign-trackers are more
susceptible to behavioral control by discrete food- and drug-paired cues and have a greater propensity for cue-
induced reinstatement or relapse. Using this animal model, we have found that the paraventricular nucleus of
the thalamus (PVT) plays a critical role in incentive learning processes and in regulating individual differences
in relapse propensity. The PVT appears to act as a node that integrates “top-down” and “bottom-up” input to
regulate cue-driven behaviors, but the subcortical circuitry subserving incentive salience attribution remains to
be determined. The research goal of this administrative supplement is to identify the neurochemical signature
of the PVT under baseline conditions and that which emerges as a consequence of cue-reward learning. In
addition, we will determine whether manipulations of a subcortical pathway, that from the lateral hypothalamus
(LH) to the PVT, alter the neurochemical profile of the PVT in conjunction with changes in behavior. This work
is a natural extension of that proposed in the parent award and in line with the overarching goal: to identify
critical components of the neural circuitry that contribute to addiction liability.

## Key facts

- **NIH application ID:** 11012003
- **Project number:** 3R01DA054094-03S1
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **Principal Investigator:** Shelly Beth Flagel
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $41,055
- **Award type:** 3
- **Project period:** 2021-09-30 → 2026-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11012003

## Citation

> US National Institutes of Health, RePORTER application 11012003, Probing the role of a hypothalamic-thalamic-striatal circuit in cue-driven behaviors (3R01DA054094-03S1). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/11012003. Licensed CC0.

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