# Investigating Ensemble Activity Dynamics of a Thalamo-Striatal Circuit Regulating Alcohol Seeking

> **NIH NIH F31** · MEDICAL UNIVERSITY OF SOUTH CAROLINA · 2024 · $46,609

## Abstract

PROJECT SUMMARY
Alcohol use disorder (AUD) is a devastating condition that affects 29.5 million people aged 12 and older. AUD is
classically characterized by a loss of behavioral control, particularly in the face of negative consequences,
resulting in a loss of inhibitory control, or disinhibition, that may normally suppress alcohol seeking. Considering
this, it is critical to investigate mechanisms associated with disinhibition. One major barrier to investigating AUD
progression is understanding specific cell populations that may normally serve to suppress alcohol seeking but
become disinhibited following dependence. While our knowledge of neuronal ensembles in alcohol dependence
remains limited, studies on the paraventricular thalamus (PVT) projection to the nucleus accumbens (NAc) in
regulating sucrose seeking have revealed distinct neuronal ensembles that emerge across the course of
learning. These studies indicate that PVTàNAc encodes ensembles of inhibited neurons that function as a
“brake” on reward-seeking. Extending these findings to examine how alcohol influences thalamo-striatal neuronal
ensembles is imperative for targeting inhibitory ensembles that may attenuate alcohol-seeking behaviors. My
preliminary data suggest that broad optogenetic activation of PVTàNAc neurons reduces alcohol-seeking,
evidenced by decreased active lever presses and alcohol deliveries during an operant head-fixed task in
nondependent mice. Conversely, optogenetic inhibition of PVTàNAc neurons releases this “brake” and
promotes active lever pressing, even in the face of behavioral suppressors. Importantly, after inducing alcohol
dependence via chronic intermittent ethanol (CIE) exposure, presentation of behavioral suppressors, including
direct activation of PVTàNAc neurons, no longer reduces alcohol seeking, indicative of a functional uncoupling
of this circuit leading to behavioral disinhibition. These current data suggest that PVTàNAc neurons may serve
as an exciting new target for studying how chronic alcohol induces disinhibition at the level of neuronal ensemble
activity. To date, no work has explored single-cell manipulation or two-photon calcium imaging of PVTàNAc
neuronal ensembles in regulating alcohol seeking before and after alcohol dependence. The focus of this
proposal therefore, is to identify and manipulate specific PVTàNAc neuronal ensembles that may be altered
after dependence. My overarching hypothesis is that inhibitory neuronal ensemble activity in PVTàNAc will best
decode alcohol-seeking behaviors and become persistently inactivated following ethanol dependence reducing
feedforward inhibition onto PV-INs. Aim 1 will measure calcium dynamics of PVTàNAc neurons in vivo to identify
unique neuronal ensembles that emerge during alcohol seeking. I will then manipulate specific PVTàNAc
neurons that may be altered before and after alcohol dependence. Aim 2 will assess how inputs from PVT onto
parvalbumin neurons in the nucleus accumbens may be alte...

## Key facts

- **NIH application ID:** 11071094
- **Project number:** 1F31AA032197-01
- **Recipient organization:** MEDICAL UNIVERSITY OF SOUTH CAROLINA
- **Principal Investigator:** Amy L Ward
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $46,609
- **Award type:** 1
- **Project period:** 2024-09-01 → 2027-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11071094

## Citation

> US National Institutes of Health, RePORTER application 11071094, Investigating Ensemble Activity Dynamics of a Thalamo-Striatal Circuit Regulating Alcohol Seeking (1F31AA032197-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/11071094. Licensed CC0.

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