Neuroanatomical and molecular architecture of high- and low-level circuits controlling orofacial movements

Project 4 Summary Motor circuits in the vertebrate brain are arranged hierarchically. Low-level circuits in the brainstem and spinal cord – such as the oscillators and pattern generators that control breathing and locomotion – can autonomously generate basic motor patterns. High-level motor circuits allow animals to learn and adapt movements, detect and correct errors, predict the cost and benefits of actions, and assemble movements into complex sequences to attain behavioral goals over long time scales. High-level circuits do not generally control movements directly, rather, they engage and coordinate the basic motor actions produced by low-level circuits during complex behavior. Low-level circuits in turn integrate an array of inputs from many high-level areas to synthesize the motor commands that drive motoneurons and muscles. In this Project, we focus on a molecular and anatomical dissection of the structure of high- and low-level circuits that are responsible for controlling orofacial movements, and the structure of the circuits connecting high- and low-levels of the motor system hierarchy. Orofacial movements are amongst the most precisely controlled movements within the mammalian repertoire for movements and support behaviors most critical for survival – the consumption of food and water, respiration, and communication. Using a suite of tools for viral genetic circuit tracing, whole-brain imaging, single-neuron reconstruction, and molecular labeling, we will first determine the architecture of low-level circuitry in the mouse medulla responsible for orofacial movement at the level of single-cell axonal morphologies. Second, we will determine the brain- wide distribution of cells that are synaptically connected to low-level orofacial motor circuits and responsible for their control. Third, we will determine the structure of descending pathways from higher-order orofacial motor regions that connect to low-level medullar circuits. Finally, we will determine which elements of low-level motor circuits are under direct high-level control at the level of molecularly defined cell types. All told, this investigation will provide a blueprint of a critical motor system in the mammalian brain across levels of the motor system hierarchy.