# Descending Control of Orofacial Behavior

> **NIH NIH U19** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2021 · $549,327

## Abstract

Project 3. Abstract
Descending control of orofacial behavior (Kleinfeld lead; Mukamel, Svoboda, Wang)
 This Research Project will define the connectivity and neural mechanisms of descending control by motor
cortex of orofacial behavior. Orofacial movements can be rhythmic and coordinated with each other. However,
individual movements can also be specifically controlled to achieve behavioral goals, such as consuming a
reward at a particular location and time. We will use a behavioral assay in which mice have to make a
directional tongue movement at a particular time to receive a reward. This further serves as an example of set-
point control. The brainstem level controls for licking are driven by the motor neurons in the hypoglossal
nucleus whose activity in turn is modulated by premotor neurons in the intermediate nucleus of the reticular
formation. Our studies will explore the anatomical connectivity, i.e. “Components” and signal flow, i.e., ”Wiring
Diagrams” that converge on this region of the reticular formation. We will further refine the description of
hypoglossal premotor subregions, nominally referred to here as “hIRt”, that are relevant to licking.
 Our preliminary data indicates that motor cortex can direct the timing of licking bouts and direction of licking,
but not the timing of individual licks. We will trace these command signals from the motor cortex through the
superior colliculus and into the hIRt. We will measure neural signals in another descending pathway from the
basal ganglia that converges on the superior colliculus and the hIRt. We will measure how these descending
inputs are synaptically coupled to defined neuron types in the hIRt. Together this project will provide a
mechanistic account of how descending signals from multiple sources are integrated at the level of premotor
neurons in the brainstem, complementing our studies on projections that control the set-point of whisking
(Project 2).
 An additional focus will set the stage for the next generation dissection of the neural circuits in the
brainstem. This requires molecular profiling of specific cell classes to provide transcriptomes that will facilitate
future fine-grained analyses, including genetic labeling, manipulation, and transsynaptic tracing. Specific
populations of premotor neurons will be isolated by transsynaptic labeling and mRNA will be isolated using
Translating Ribosome Affinity Purification (TRAP), a technology that isolates mRNAs associated with
translating ribosomes and is especially favorable in the densely myelinated brainstem. This is followed by deep
sequencing and yields a new method, TRAP:Seq.

## Key facts

- **NIH application ID:** 10199076
- **Project number:** 5U19NS107466-04
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **Principal Investigator:** David Kleinfeld
- **Activity code:** U19 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $549,327
- **Award type:** 5
- **Project period:** 2018-09-15 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10199076

## Citation

> US National Institutes of Health, RePORTER application 10199076, Descending Control of Orofacial Behavior (5U19NS107466-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10199076. Licensed CC0.

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