# Neuroengineering a Robust Vocal Learning Phenotype in Mice as a Model for Treating Communication Disorders

> **NIH NIH R01** · ROCKEFELLER UNIVERSITY · 2021 · $1,061,246

## Abstract

Abstract
The goal of this Transformative R01 project is to develop genetic strategies for neuroengineering a robust
vocal learning phenotype in mice, which may yield the first mammalian model for treating human vocal
communication disorders. Up to 10% of humans have some sort of communication dysfunction in their lifetimes
(Speech and Language Impairments, NICHCY, 2011), yet there is no genetically tractable system for
enhancing or repairing brain circuits involved in speech. We recently discovered that mice, which are highly
tractable, show evidence of a rudimentary vocal learning phenotype. Specifically, mice have some features
once thought unique to humans and other vocal learning species, including the ability modify ultrasonic
vocalizations (USVs) based on context; a forebrain vocal circuit that is active during vocalizing, is required for
frequency modulation and organization of syllables, and that directly connects to brainstem motor neurons that
control the larynx; and syllable sequencing deficits when given a FoxP2 mutation known to cause phoneme
sequencing dyspraxia in humans. However, compared to humans and songbirds, these phenotypes are much
more limited in mice. These and other findings led us to hypothesize that similar to natural variation in ability
among vocal learners, presumed vocal non-learners may exhibit vocal learning-like phenotypes along a
continuum of complexity across species. In this context, given the presence of the basic neuroarchitecture in
mice considered obligate for vocal learning in categorical species, we postulate that the mouse vocal system
and associated behaviors may be liable to enhancement, thereby providing a foundation for the development
of novel and effective strategies for ameliorating disorders of human vocal communication. To accomplish this,
we will exploit recent findings from our laboratory where we discovered convergent specialized gene
expression of ~50 genes in vocal brain regions of several vocal learning species, including humans and
songbirds, many of which are involved in brain pathway development. We hypothesize that evolutionary
changes in the regulation of trait-specialized genes are responsible for the emergence of more advanced vocal
plasticity and other complex behavioral traits. Our objective is to recapitulate the unique expression patterns
of these genes in mice to enhance the vocal learning phenotype at the level of connectivity, in vivo
electrophysiology, and behavior. We will do so using viral strategies, introduction of human neural stem cells,
and the generation of transgenic animals. If successful, our studies are expected to impact the field by: 1)
Establishing how vocal-learning specialized genes shape the neurocircuitry and physiology for this complex
behavior; 2) Developing a novel, genetically tractable mammalian model system for unveiling the
neurobiological details of human language and treatments for its dysfunction; and 3) Serving as a platform for
neuroengineeri...

## Key facts

- **NIH application ID:** 10241317
- **Project number:** 5R01DC018691-03
- **Recipient organization:** ROCKEFELLER UNIVERSITY
- **Principal Investigator:** Erich D Jarvis
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $1,061,246
- **Award type:** 5
- **Project period:** 2019-09-01 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10241317

## Citation

> US National Institutes of Health, RePORTER application 10241317, Neuroengineering a Robust Vocal Learning Phenotype in Mice as a Model for Treating Communication Disorders (5R01DC018691-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10241317. Licensed CC0.

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