# Sub-thalamic modulation of learning-related dimensions of PTSD.

> **NIH NIH R01** · CHILDREN'S HOSPITAL OF LOS ANGELES · 2022 · $15,898

## Abstract

PROJECT SUMMARY
 Approximately 24 million Americans suffer from Post-Traumatic Stress Disorder (PTSD). Exacerbating the
devastating nature of PTSD is its co-morbidity with depression. Defined by a lack of motivation to engage in
pleasurable activities, anhedonia is a highly prevalent and debilitating dimension of depression. While
sertraline and paroxetine, the two FDA-approved medications for PTSD, are in fact antidepressant treatments,
they are effective in approximately 50% of treated cases, emphasizing that there is room to more effectively
rescue deficits in motivation. One way to achieve this objective is to first understand how motivation is
facilitated by neuromodulators within specific neural circuitry. Among the many neuromodulators that exist,
dopamine has a rich background in the context of driving motivated behavior. However, our understanding of
dopamine’s contributions to motivational behavior comes from studies of the A10 dopaminergic cells in the
VTA and their projections. In contrast, the contributions of other distinct clusters of dopaminergic cells that are
evolutionarily conserved in the mammalian brain to motivational drive is unknown. Filling this gap will not only
significantly advance our knowledge of dopaminergic influences on motivation, but also once these
contributions are established, we can analyze across dopaminergic cell clusters, molecular perturbations that
may cause deficits in motivation and potentially identify new pharmacotherapy to rescue these deficits. Recent
work published by colleagues reported a novel role for the zona incerta (ZI), a sub-thalamic brain region, in
motivation. Given the presence of A13 dopaminergic cells in the ZI, we will combine behavioral neuroscience
techniques that assay motivational drive in mice with chemogenetic methodology and Next-Gen Sequencing to
test the hypothesis that A13 cells in the ZI influence motivation. Our work will illuminate basic neurobiology
underlying a clinically important dimension of depression (anhedonia). Positive results will shed light on how an
understudied circuit modulates normative motivational drive while being able to rescue anhedonia. This work
will position us to compare and contrast stress-induced changes across dopaminergic cell clusters in the brain
to identify unique and shared molecular pathways that could be targeted to reduce deficits in motivation.

## Key facts

- **NIH application ID:** 10488905
- **Project number:** 3R01MH120133-04S1
- **Recipient organization:** CHILDREN'S HOSPITAL OF LOS ANGELES
- **Principal Investigator:** Brian George DIAS
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $15,898
- **Award type:** 3
- **Project period:** 2020-09-04 → 2024-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10488905

## Citation

> US National Institutes of Health, RePORTER application 10488905, Sub-thalamic modulation of learning-related dimensions of PTSD. (3R01MH120133-04S1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10488905. Licensed CC0.

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