# Neural control of rhythmic orofacial movements

> **NIH NIH DP1** · DUKE UNIVERSITY · 2024 · $1,127,000

## Abstract

Abstract
Major efforts to understand how brain circuits activity gives rise to perception, mental experience, and behavior
have broadly advanced our understanding of most of the central nervous system. In contrast, the brainstem
circuit that connects the brain to patterned muscle outputs is arguably the least understood. The brainstem also
generates rhythms on its own. Networks of premotor neurons (central pattern generators) control and
autonomously coordinate rhythmic movements such as breathing, chewing, drinking, swallowing, and
vocalization. Understanding this neural coordination is fundamentally important for a host of survival-critical
conditions. For example, disorganization of breathing and swallowing leads to choking, which is a leading cause
of death among children and elderly, and a common manifestation of neurodegeneration. Current understanding
of brainstem central pattern generators, such as the breathing oscillator, are derived from neurophysiological
recordings, but these data are extremely limited. Central pattern generators for drinking and swallowing have
not been definitely identified and there is no suitable model system for study neural coordination of multiple
rhythmic movements. A challenge has been applying emerging technologies for large-scale neurophysiology
and mechanistic circuit dissection to the brainstem in behaving animals. I propose a transformative research
program to map and dissect brainstem central pattern generators that coordinate orofacial rhythms. First, using
approaches recently established in my lab for large-scale high-density electrophysiology mapping of multi-
regional neural circuits, we will map the premotor networks for licking, breathing, and swallowing in brainstem of
behaving mice. Using circuit tracing tools, we will further delineate the organization of these premotor circuits in
terms of their molecular cell types and connectivity. Using this roadmap, we will probe interactions between these
premotor circuits using simultaneous recordings of their activities in conjunction with controlled perturbation of
individual circuits. Finally, we will dissect how brainstem intrinsic rhythms interact with descending volitional
control (analogous to how we are able to adjust our breath when we vocalize) by simultaneously recording the
higher motor centers with the downstream brainstem circuits in mice performing volitional drinking. The outcome
will shed light on why life-threatening symptoms occur in many forms neurological malfunctions that all trace
their roots to the brainstem, paving the way for development of therapeutic interventions.

## Key facts

- **NIH application ID:** 10923310
- **Project number:** 1DP1NS142432-01
- **Recipient organization:** DUKE UNIVERSITY
- **Principal Investigator:** Nuo Li
- **Activity code:** DP1 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $1,127,000
- **Award type:** 1
- **Project period:** 2024-09-19 → 2029-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10923310

## Citation

> US National Institutes of Health, RePORTER application 10923310, Neural control of rhythmic orofacial movements (1DP1NS142432-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10923310. Licensed CC0.

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