# Beyond dopamine: dual neuromodulator regulation of motor variability and learning

> **NIH NIH F32** · DUKE UNIVERSITY · 2024 · $79,284

## Abstract

Project Summary
Learning and performing complex skills such as speech or music requires precise control of motor variability.
While elevated motor variability can spur the learning of new behaviors, excessive variability can impair
performance of learned skills. How the brain controls motor variability during learning and in expert
performance remains unclear. Intriguingly, the basal ganglia (BG) is an important source of motor variability in
both health and disease, and is a key site where dopamine (DA) reinforces more successful behaviors. Indeed,
the BG’s ability to regulate motor variability is especially critical for complex sequential skills such as speech,
where variability can arise at both the level of elementary motor “syllables” and the sequential “syntax” in which
these syllables are organized. How DA signaling in the BG influences motor variability during the learning of
complex sequential skills akin to speech or music is poorly understood. Moreover, rather than acting alone, an
emerging view is that DA signaling is strongly modulated by other signaling molecules, such as adenosine
(Ado), which may track the metabolic costs associated with extensive motor practice. Here I will characterize
how Ado and DA release in the BG are related to each other, to motor variability, and to the learning of
vocal motor sequences. In direct service of BRAIN initiative goals, I will combine cutting-edge computational
and optical tools along with an innovative molecular-genetic approach to dissect both neuromodulator and cell-
type specific contributions to motor variability and learning. My Specific Aims are: 1) To image Ado and DA in
the sBG during juvenile vocal learning. 2) To establish the necessity of sBG Ado to regulate variability and test
for a direct link between Ado and DA release. 3) To genetically tag “indirect” and “direct” spiny neuron types
and assess how Ado modulates their activity to influence song variability. Individually, each aim will move
beyond a single-neuromodulator model of BG skill learning, and collectively they will help reveal fundamental
mechanisms that control motor variability across learning and performance. I will conduct this research under
the supervision of Drs. Richard Mooney, Josh Huang, and John Pearson, an interdisciplinary team of
accomplished mentors that provides me with complementary expertise in behavioral, systems neuroscience,
computational, and cutting-edge genetic techniques. In addition to my deep interest in understanding natural
forms of behavioral learning, I bring my own expertise in analyzing behavior in concert with optical methods.
This proposal will allow me to both deepen and broaden my expertise, and will provide significant training in
novel behavioral, computational, genetic, and imaging techniques. This integrative approach to systems
neuroscience and natural behavior will enhance my capabilities as an independent researcher while
addressing BRAIN Initiative goals.

## Key facts

- **NIH application ID:** 10800679
- **Project number:** 5F32MH132152-02
- **Recipient organization:** DUKE UNIVERSITY
- **Principal Investigator:** Drew Clinton Schreiner
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $79,284
- **Award type:** 5
- **Project period:** 2023-07-01 → 2026-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10800679

## Citation

> US National Institutes of Health, RePORTER application 10800679, Beyond dopamine: dual neuromodulator regulation of motor variability and learning (5F32MH132152-02). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/10800679. Licensed CC0.

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