# Mechanisms for internally and externally guided sensorimotor learning

> **NIH NIH R01** · DUKE UNIVERSITY · 2020 · $428,372

## Abstract

Neurons in the ventral tegmental area (VTA) play a key role in motor learning, and neurological diseases
that affect VTA neurons or their targets in the basal ganglia (BG) severely disrupt behavior. Notably, much
of our understanding of how the VTA functions in motor learning has relied on paradigms that employ
external reward or punishment and involve relatively slow and simple behaviors, such as lever pressing or
licking. In contrast, many of our most complex and valued behaviors, such as speech and musical
expression, can be learned without external reinforcement, suggesting that their learning is internally
reinforced. Further, internally reinforced behaviors such as speech or musicianship require highly complex
and rapid motor sequences and are more readily acquired during juvenile sensitive periods. How the VTA
interacts with the BG to mediate complex forms of internally and externally reinforced auditory-motor
learning remains unknown. Here we propose to identify how the VTA and BG interact to mediate different
forms of auditory-motor learning using a novel combination of intersectional genetic methods to selectively
ablate VTA neurons, microdialysis, calcium imaging and optogenetic manipulation of VTA terminals and BG
neurons combined with rapid and temporally precise behavioral manipulations. These approaches will be
used to test the hypothesis that the VTA functions as a “critic” that evaluates auditory feedback and
instructively modifies BG premotor activity, which in turn drives internally and externally reinforced auditory-
motor learning. Resolving how VTA-BG circuits mediate these forms of learning are critical issues for
understanding motor plasticity in health and disease. In fact, speech pathologies typify various diseases
that affect VTA-BG circuitry, while mutations that disrupt dopamine-mediated signaling in the BG also impair
vocal learning. Therefore, the proposed research can shed light on the neural circuit mechanisms that
enable complex internally and externally reinforced behavioral learning while also revealing how dysfunction
in these circuits interferes with the learning and execution of communicative behaviors.

## Key facts

- **NIH application ID:** 9959211
- **Project number:** 5R01NS099288-05
- **Recipient organization:** DUKE UNIVERSITY
- **Principal Investigator:** Richard D Mooney
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $428,372
- **Award type:** 5
- **Project period:** 2016-09-30 → 2021-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9959211

## Citation

> US National Institutes of Health, RePORTER application 9959211, Mechanisms for internally and externally guided sensorimotor learning (5R01NS099288-05). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/9959211. Licensed CC0.

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