Overall - Abstract High- and low-level computations for coordination of orofacial motor actions Neuronal circuits in the brainstem integrate control of life-sustaining motor actions, such as breathing and feeding, with exploratory motor actions, such as sniffing, licking, nose and head turning, and, for rodents, whisking. All of these contain a rhythmic component that is entrained by the breathing cycle. What are the underlying circuits that produce these motor actions and how are they coordinated into flexible behaviors? Our hypothesis is that high-level rhythmic signals use feedback to modulate the phase of low-level oscillator activity on a cycle-wise basis. High-level broadband signals also regulate set-point and posture of effectors. Together, low- and high-level signals lead to coordinated and precise rhythmic behaviors to achieve sensory goals. We address our hypothesis using two theoretical concepts and a plethora of experimental procedures. One theoretical concept is control theory. This concept emphasizes internal models, that is, computations that yield signals to drive a physical plant, such as the vibrissae or the tongue, that respect the innervation of the musculature. Control theory also emphasizes the role of feedback signals to correct the timing of rhythmic actions. The second theoretical concept is coupled oscillators circuits, one for each rhythmic action with an overall "coordinator". These guide schemes for the continual adjustment rhythmic action phases to form a precise behavior. Theoretical guidance was pivotal toward the discovery of the oscillator for whisking, identify a mechanism brain used to create a hierarchy of oscillators, and identifying modularity in the control of movement. We seek to discover a second fundamental oscillator in the brainstem, one that controls chewing and licking. In parallel, we will complete a biomechanical model of the tongue that includes changes in shape and turgidity based on motor innervation of the muscles and the control of blood flow by local parasympathetic neurons. Together with whisking and joint vibrissa and head movement, these are a trifecta of targets for high-level control. A novel concept in our proposal is the fine control of rhythmic motion by high-level feedback to refine the relative timing of different rhythm motor actions. Thus head position, tongue position, possibly whisker position are optimized in the context of a behavior. We address this possibility through three interdependent approaches: anatomical tracing of molecularly identified high-level cell types to molecularly identified low-level targets in the medulla; recording and perturbing signals in superior colliculus that influence head orientation and whisking; and recording and perturbing cortical signals that influence licking. The collective expertise of our Team bridges state-of-the-art anatomical, behavioral, computational, molecular, and physiological technologies. We have historically adhered to the highest standards in experimentation, analysis, and theory. Critically, we are joined by top trainees in a diverse workforce committed to progress on motor control, and we are dedicated to educating our trainees in a culture of curiosity and scholastic excellence.

Narrative High- and low-level computations for coordination of orofacial motor actions Neuronal circuits in the brainstem control life-sustaining functions, including breathing and other rhythmic orofacial motor actions that underlie both exploration and consumption, and that must be performed without interruption from the moment of birth. Our hypothesis is that high-level rhythmic signals modulate the phase of low-level rhythmic activity on a cycle-wise basis, and high-level broadband signals regulate both set-point and posture to form coordinated and precise rhythmic behaviors. Guided by our hypothesis, we use and advance the tools of modern neuroscience to add informative labels to individual neurons in the brainstem, place these cells within circuits, connect circuits with motor actions, and coordinate different actions into behaviors.