Tuning prefrontal brain circuits to help motivation and pleasure

Neuromodulatory control of prefrontal circuit function and reward-seeking

NIH-funded research Weill Medical Coll of Cornell Univ · NIH-11247461

Testing whether targeting specific brain cells in the prefrontal cortex can quickly improve motivation and pleasure for people with depression.

Quick facts

Grant typeR01 grant
Study typeNIH-funded research
Funding institutionWeill Medical Coll of Cornell Univ NIH-funded
Lab location1 site (New York, United States)
Project IDNIH-11247461 on NIH RePORTER

What this research studies

This research looks inside the prefrontal cortex — the brain area that helps decide if a reward is worth the effort — to understand why people with depression lose motivation and pleasure. The team uses advanced tools that can switch signaling in specific nerve cells (including somatostatin-expressing interneurons) on and off to see how those changes affect effort-based reward-seeking and mood-related behavior. They pair these rapid signaling experiments with studies of synapse formation to learn how short-term circuit changes might lead to longer-lasting antidepressant effects. Most work is done in lab models at Weill Cornell, with the goal of informing future treatments for patients.

Who could benefit from this research

Good fit: People with major depressive disorder who struggle with low motivation or loss of pleasure could be candidates for future clinical work based on these findings.

Not a fit: Patients whose symptoms are not driven by effort-related motivation or whose depression responds to other mechanisms may be less likely to benefit from this specific approach.

Why it matters

Potential benefit: If successful, this work could point to faster-acting therapies that restore motivation and reduce anhedonia in people with depression.

How similar studies have performed: Prior preclinical studies, including work on rapid-acting antidepressants and synapse growth, have shown promise in changing motivation and mood in animals, but translation to human benefit remains unproven.

Where this research is happening

New York, United States

Researchers

About this research

  1. This is an active NIH-funded research project — typically early-stage science, not a clinical trial accepting patient enrollment.
  2. Some NIH-funded labs run parallel clinical studies or seek volunteers for related work. To check, contact the principal investigator or institution listed above.
  3. For full project details, budget, and progress reports, visit the official NIH RePORTER page below.
Last reviewed 2026-06-13 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.