# Prefrontal somatostatin interneurons in action valuation processing and motivational anhedonia

> **NIH NIH F30** · WEILL MEDICAL COLL OF CORNELL UNIV · 2020 · $50,520

## Abstract

PROJECT SUMMARY
 Major depressive disorder (MDD) is a highly prevalent and debilitating mood disorder that is diagnosed
based on a mixture of symptoms, but anhedonia—decreased interest in rewarding activities—is a core feature.
Anhedonia can be caused by an inability to experience pleasure or by a lack of motivation to work towards
obtaining a reward. Every decision to exert effort to obtain a reward involves action valuation computations—
essentially a cost-benefit analysis of whether the positive value of the expected outcome of an action
outweighs the negative value of the expected effort associated with that action. The anterior cingulate cortex
(ACC), a stress-sensitive region of prefrontal cortex (PFC), has been consistently implicated in action valuation
computations across species. Whether and how dysfunctional action valuation computations drive anhedonic
symptoms in stress-related psychiatric disease is unclear. While extensive, groundbreaking work has
characterized the effects of stress on PFC glutamatergic circuitry, less is known about the role of local
inhibitory circuitry in stress-induced depressive-like behaviors, despite substantial evidence for changes in the
inhibitory system in MDD patients. This work will investigate the role of one cellular subtype, somatostatin
(SST)-expressing interneurons, in driving both healthy reward-seeking and chronic stress-induced anhedonic
behavior. Our hypothesis is that SST interneurons facilitate action valuation computations by dynamically
regulating synaptic inputs to the ACC and that hyperactivity in SST cells disrupts this process in chronic stress
states. To test this, we will record the activity of the ACC SST interneuron population through a chronically
implanted optical fiber (fiber photometry) in awake, freely behaving mice performing an effortful reward-seeking
task under normal and chronically stressed conditions. We will then optogenetically manipulate the activity of
these cells to identify specific causal roles for SST interneurons in driving healthy and pathological reward
processing. This investigation will fill a substantial gap in our understanding of stress-induced anhedonic
behavior by focusing on a sparse but essential cell population that is understudied in the context of stress and
depression.
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## Key facts

- **NIH application ID:** 9998737
- **Project number:** 5F30MH115622-04
- **Recipient organization:** WEILL MEDICAL COLL OF CORNELL UNIV
- **Principal Investigator:** Robert N Fetcho
- **Activity code:** F30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $50,520
- **Award type:** 5
- **Project period:** 2017-09-15 → 2021-09-14

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9998737

## Citation

> US National Institutes of Health, RePORTER application 9998737, Prefrontal somatostatin interneurons in action valuation processing and motivational anhedonia (5F30MH115622-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9998737. Licensed CC0.

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