# Characterizing the Activity Dynamics and Function of Thalamostriatal Circuits During Opioid Seeking

> **NIH NIH F31** · MEDICAL UNIVERSITY OF SOUTH CAROLINA · 2021 · $43,491

## Abstract

PROJECT SUMMARY
Opioid use disorder (OUD) is a major epidemic within the United States, and this issue is exacerbated by the
highly addictive nature of opioids. When presented with drug-associated environmental cues, patients suffering
from OUD are more likely relapse to compulsive opioid seeking and taking, even with the risk of significant
negative consequences. Despite knowing this, how opioid-associated cues engage brain reward circuits for the
control of opioid-seeking behaviors is unclear. Having a better understanding of how cues affect brain reward
circuits to provoke drug seeking could provide better insight into novel therapeutics for the treatment of OUD.
 One particular brain region known to be engaged by reward-associated cues is the paraventricular
nucleus of the thalamus (PVT). The PVT is architecturally organized between areas that are associated with
conditioned reward-seeking behaviors, and has been demonstrated to play roles in appetitive motivation,
feeding, memory, and natural reward or drug-seeking behaviors. In addition to these inputs, the PVT itself has
dense opioid receptor (OR) expression, which is known to modulate PVT activity. Furthermore, my data reveals
that opioid receptors are specifically expressed on PVT neurons that project to the nucleus accumbens
(PVTàNAc), a pathway that provides a critical “brake” for reward seeking. Despite this knowledge, the influence
of opioid use and the presentation of opioid-associated cues on PVTàNAc activity is unknown. Furthermore,
the function of this pathway for opioid seeking is unknown. Here I propose the central hypothesis that
pPVTàNAc neurons are inhibited during opioid use and by the presentation of opioid-associated cues, and that
this inhibition is required for opioid seeking. These data are supported by my extensive preliminary datasets,
wherein I show that PVTàNAc neurons are inhibited during the presentation of heroin predictive cues, whereas
optogenetically mimicking this inhibition in extinction conditions drives immediate and voracious goal-directed
heroin seeking. Using innovative techniques developed in our laboratory, I will test my hypothesis with two
experiments. In Aim 1, I will use a novel head-restrained heroin self-administration protocol that allows
simultaneous in vivo two-photon calcium imaging to determine the precise activity dynamics of pPVTàNAc
neurons during acquisition, extinction, and reinstatement phases of self-administration. In Aim 2, I will use
behavioral optogenetics to determine the function of pPVTàNAc neurons for cue-induced reinstatement of
heroin seeking.
 Together, these experiments will identify the activity dynamics and function of precisely-defined PVT
output neurons for heroin seeking. This information will provide an overall better understanding of OUD for the
development of novel therapeutics.

## Key facts

- **NIH application ID:** 10234487
- **Project number:** 1F31DA052186-01A1
- **Recipient organization:** MEDICAL UNIVERSITY OF SOUTH CAROLINA
- **Principal Investigator:** Kelsey Vollmer
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $43,491
- **Award type:** 1
- **Project period:** 2021-04-01 → 2024-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10234487

## Citation

> US National Institutes of Health, RePORTER application 10234487, Characterizing the Activity Dynamics and Function of Thalamostriatal Circuits During Opioid Seeking (1F31DA052186-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10234487. Licensed CC0.

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