# Confluence of high- and low-level signaling for the control of orofacial rhythmic motor actions

> **NIH NIH U19** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2024 · $589,041

## Abstract

Project 1. Abstract
Confluence of high- and low-level signaling for the control of orofacial rhythmic motor actions
 Orofacial actions are nominally comprised of two components: a rhythm that can be entrained by the
breathing oscillator, i.e., the preBötzinger complex (pBötC), and a broadband component that directs the actuator
to the region-of-interest. Project 1 addresses both low-level, via pBötC, and high-level means to coordinate the
rhythmic components of actions into a behavior. We hypothesize that the precise timing of each constituent
action is continually adjusted through the merge of pBötC and reflex input within the brainstem and a sensory-
derived, high-level feedback signal(s). This Project focuses primarily on whisking and the synergy of whisking
and head turning. It serves, in part, as a blueprint for proposed studies on the low- and high-level coordination
of licking and chewing in all other Projects.
 Our first goal is to construct theoretical models of coupled oscillator circuits that provide insight into the
signals needed to control the phase of multiple low-level oscillators through a single high-level coordinator. The
models are abstractions of biological reality. Yet they are tractable and provide guidance on plausible scenarios
for the fine control of timing in orofacial motor actions whose movements are coordinated to form behaviors.
 At the low-level, we consider the nature of the inputs from the breathing oscillator pBötC in mice. Are the
initial phases of each motor action, relative to breathing, set by phase-specific projections from the pBötC? Or
are they set by the synapses and promotor circuits that transform the pBötC inputs? We use deep imaging of
pBötC projection neurons that are functionally labeled by their molecular phenotype and their downstream
target(s). These data will constrain the capability of low-level signals to provide the initial phase relations among
different motor actions.
 At the high-level, we consider signals that originate in the deep motor layers of the superior colliculus (SCm)
that provide inputs to vibrissa motoneurons and, from our preliminary data, further provide input to whisking
oscillator cells. We will examine how signals from the SCm shift the timing of whisking relative to pBötC signals
using deep imaging and functional perturbations in mice. We will also test the role of the SCm to coordinate and
finely control concurrent motor actions in freely behaving rats that perform an orientation-search-consumption
task. The reliability of the combined motor actions, analyzed with respect to the variability of optical and
extracellular recordings from SCm neurons, directly tests our hypothesis and supports or falsifies specific
models. The results will reveal the interplay among autonomous low-level and conditional high-level signaling.

## Key facts

- **NIH application ID:** 10930307
- **Project number:** 1U19NS137920-01
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **Principal Investigator:** David Kleinfeld
- **Activity code:** U19 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $589,041
- **Award type:** 1
- **Project period:** 2024-08-15 → 2029-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10930307

## Citation

> US National Institutes of Health, RePORTER application 10930307, Confluence of high- and low-level signaling for the control of orofacial rhythmic motor actions (1U19NS137920-01). Retrieved via AI Analytics 2026-06-12 from https://api.ai-analytics.org/grant/nih/10930307. Licensed CC0.

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