UC San Diego

Neural circuits are the fundamental substrate for brain computations and, ultimately, behavior. The sensorimotor processing that mediates sensory-driven behaviors relies on inputs from the environment, transduced by specialized receptors, and transformations of these inputs into motor outputs, constrained by circuit architecture. The trigeminal-facial brainstem system, which exercises the lowest level of control over vibrissa behavior, provides an ideal framework for understanding the neural circuitry underlying sensorimotor processing. While the anatomy of trigeminal inputs and facial outputs has been studied for over a century, the organization of circuits instantiating such processing remains obscure. Here, I explore this organization with three related studies on mouse trigeminal and facial brainstem circuitry. First, I delineate a complete disynaptic circuit from mechanosensory trigeminal inputs to facial motor outputs using single and dual labeling with traditional tracers, engineered viruses, and transgenic animals. I show that a morphologically distinct set of interneurons receives monosynaptic inputs from peripheral trigeminal afferents, and projects monosynaptically to the division of facial nucleus controlling vibrissa movement. These interneurons are primarily glutamatergic, suggesting that this circuit may mediate the fast, positive feedback employed in vibrissa-based active sensation. Second, I examine the large scale genetic organization of inputs and nuclei within the trigeminal brainstem. Using targeted microinjections to the face, I generate a micrometer- resolution inventory of central trigeminal afferent projections. I develop a method to register this inventory with a genome-wide gene expression database of the mouse brain. With these co-registered datasets, I use statistical learning approaches to explore both the relationship between connectivity and regionalization and the role of sparse sets of genes in determining trigeminal organization. Finally, I evaluate the specialized receptors that encode vibrissa sensory information. I develop a preparation for two photon imaging of sensory endings, then characterize the reliable mechanical deformations of different receptor types that result from vibrissa deflections. Altogether, this work provides novel insights into the architecture of low level sensorimotor processing, from peripheral sensory transduction, through individual circuits, to overarching organization