# Investigating the Role of GABAergic Interneurons in the Dorsomedial Striatum in Goal-Directed Behavior

> **NIH NIH F30** · UNIVERSITY OF PENNSYLVANIA · 2024 · $53,974

## Abstract

Project Summary:
Goal-directed behaviors aim to maximize rewards in changing environments. Abnormalities in goal-directed
behavior are a feature of a range of neuropsychiatric diseases and are functionally impairing. The dorsomedial
striatum (DMS) is critical for the execution of goal-directed behavior. Within the DMS, the role of sparse
GABAergic interneurons in behavior is of increasing interest. Parvalbumin-positive (PV+) fast-spiking
interneurons (FSIs) exhibit sensory-guided choice- and action initiation-related activity, while somatostatin-
positive (SST+) low-threshold spiking interneurons (LTSIs) exhibit novel reward-related activity that decays
throughout operant learning. However, the role of FSIs and LTSIs in value-based goal-directed behavior is not
known. Both subtypes receive cortical inputs that guide value-based choice and signal unexpected outcomes.
FSIs are soma-targeting, allowing them to directly control principal neuron spiking and optimize ensemble
recruitment, while LTSIs are dendritic-targeting, allowing them to modulate excitability of principal neurons in
response to cortical inputs. Using this framework as a starting point would suggest striatal FSIs mediate updating
of actions by silencing previously active SPN ensembles, while LTSIs may facilitate reward-history integration
by decreasing SPN excitability and attenuating sensitivity to incoming cortical information biasing choice. LTSIs
additionally exert inhibition onto midbrain dopaminergic afferents to the DMS, which play a role in the modulation
of motor vigor. My preliminary data demonstrate that LTSIs exhibit unexpected outcome-related activity, and that
constitutive inhibition of LTSIs increases motor vigor. I therefore hypothesize that DMS FSIs exhibit pre-choice
activity to refine action selection and inhibit competing actions, especially as contingencies change. Conversely,
I hypothesize that DMS LTSI activity is higher in the setting of unexpected rewards, and thus helps constrain
vigor and facilitate integration of evidence when contingencies change. To test these hypotheses, I have
developed a head-fixed two-alternative forced choice behavioral paradigm in mice that assays the effect of
varying relative reward values, reward probabilities, and net reward environment on value-based goal-directed
choice and motor vigor. With this task, I aim to elucidate FSI and LTSI activity patterns during value-based
behavior using fiber photometry and 1-photon miniscope recordings, and causally manipulate their
activity using optogenetics. These findings will contribute to a growing evidence base on the role of striatal
microcircuitry in striatal function and goal-directed behavior, with potential translational relevance suggested by
evidence implicating striatal interneurons in a range of neuropsychiatric disease presentations.

## Key facts

- **NIH application ID:** 10900356
- **Project number:** 1F30MH136699-01
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** Evan Alexander Iliakis
- **Activity code:** F30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $53,974
- **Award type:** 1
- **Project period:** 2024-04-01 → 2028-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10900356

## Citation

> US National Institutes of Health, RePORTER application 10900356, Investigating the Role of GABAergic Interneurons in the Dorsomedial Striatum in Goal-Directed Behavior (1F30MH136699-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10900356. Licensed CC0.

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