# Differential Role of Striatal Direct and Indirect Pathway Output in the Acquisition and Expression of Instrumental Action Selection.

> **NIH NIH F31** · BOSTON UNIVERSITY MEDICAL CAMPUS · 2022 · $46,752

## Abstract

PROJECT SUMMARY / ABSTRACT
The striatum is the main input region of the basal ganglia, receiving and integrating massive amounts of sensory,
motor and cognitive information in order to output, through activation of the direct and indirect pathways,
appropriate actions in response to particular external stimuli and contexts. Imbalances in the activity of the
striatum have been implicated in movement disorders like Parkinson’s disease and disorders of action selection
and learning like addiction and obsessive compulsive disorder. This range of diseases are characterized by
distinct behavioral deficits ranging from immediate action selection to learning-related adaptive responses.
However, it is still unknown how simultaneous output of the two main pathways of the striatum support immediate
action selection and how these dynamics evolve across learning to support adaptive decision making and action
selection. The purpose of this proposal is to determine how activity in direct and indirect pathways
evolves on timescales ranging from 100s of ms to days to support learning and performance of
appropriate, instrumental actions.
Literature evidence suggests that the anterior and posterior regions of the dorsomedial striatum (aDMS and
pDMS) are a locus for the performance and acquisition, respectively, of goal-directed actions. We have designed
three different aims in which we will address how simultaneous activation of the direct and indirect pathways in
the aDMS and pDMS leads to proper performance and acquisition of instrumental behaviors. The first aim will
test how simultaneous dynamics of the direct and indirect pathways in the aDMS support context-dependent
immediate action selection by performing high-resolution 2-photon recordings of the calcium dynamics on both
pathways while mice perform a context-dependent instrumental task. We will inject D1-cre and Adora2a-cre mice
with two AAV-viral vectors containing the calcium indicator GCaMP7f, a proxy for neural activity, and the static
cre-dependent label td-Tomato to acquire cell type specificity.
The second aim will test how the dynamics of the direct and indirect pathways evolve during instrumental learning
to allow for the proper acquisition of instrumental behaviors. To answer this question, we will employ the same
imaging approach mentioned above with longitudinal recording to access the same population of pDMS cells
across days, mice will be imaged as they learn new contingencies. Lastly, our third aim will test the individual
contributions of each pathway to the acquisition of contralateral versus ipsilateral instrumental action selection
by optically inhibiting each pathway during key task events across days of training. This will be done by
selectively expressing cre-dependent inhibitory opsins in the pDMS of D1-cre and Adora2a-cre mice. Overall,
results from the proposed studies will provide fundamental understanding about how these circuits normally
function, which is a key step towards und...

## Key facts

- **NIH application ID:** 10492442
- **Project number:** 5F31MH126570-02
- **Recipient organization:** BOSTON UNIVERSITY MEDICAL CAMPUS
- **Principal Investigator:** Gabriela Alejandra Rodriguez
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $46,752
- **Award type:** 5
- **Project period:** 2021-09-20 → 2023-09-19

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10492442

## Citation

> US National Institutes of Health, RePORTER application 10492442, Differential Role of Striatal Direct and Indirect Pathway Output in the Acquisition and Expression of Instrumental Action Selection. (5F31MH126570-02). Retrieved via AI Analytics 2026-06-11 from https://api.ai-analytics.org/grant/nih/10492442. Licensed CC0.

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