Project Summary The diverse range of sensory neurons that innervate the skin underlie our ability to perceive a remarkable range of tactile stimuli and provide us with the capacity to manipulate objects, detect threats, and navigate our environment. Despite the fundamental importance of our sense of touch, little is known about how recipient neurons in the dorsal column nuclei (DCN) of the brainstem integrate primary sensory information, and how processed information is then transmitted to the brain. Anatomical tracing studies have revealed multiple, non- overlapping downstream targets of the DCN, the most prominent being the thalamus and inferior colliculus. As the node between sensory information from the periphery and central somatosensory pathways, I hypothesize that the DCN functions as a site of differential sensory integration to selectively tune output pathways to features in the environment. My proposed experiments will address this hypothesis by characterizing the tuning properties of DCN projection neurons that target the inferior colliculus and the thalamus, and by investigating how responses are constructed by inputs from peripheral sensory neurons and inhibitory interneurons. This work will overcome barriers in the field by combining novel brainstem recording methods with tools to manipulate the activity of primary sensory neurons. In doing so, my proposal will yield insights into how the DCN processes tactile information, and may also illuminate more general mechanisms by which the brain organizes sensory information. Additionally, a fundamental understanding of early somatosensory processing will inform efforts to develop neural prosthetics, as well as guide efforts to treat clinical cases where somatosensation is altered, such as mechanical allodynia after peripheral nerve injury or hypersensitivity to light touch exhibited by individuals with autism.