Synaptic mechanisms of somatosensory circuit assembly

Abstract Chronic pain is debilitating disease that affects more Americans than cancer, heart disease, and diabetes combined. Despite this significant public health problem, effective treatments are scarce and commonly prescribed opioids possess significant abuse liabilities. One possible reason for this poor translational success is that we still lack a detailed understanding of how these circuits are connected to process sensory information and their plasticity mechanisms. In our preliminary experiments we have identified important roles for trans-synaptic adhesion molecules in regulating somatosensory synapse function in the spinal cord. Here we will determine the trans- synaptic molecules that influence somatosensory synapse formation, understand how presynaptic adhesion molecules in somatosensory neurons instruct the formation and function of native synapses in the spinal cord, and establish their role in coordinating nociceptive circuit assembly to regulate pain behaviors. This proposal will use a combination of in vitro synapse induction assays, conditional gene knockout and rescue approaches, peripheral viral circuit tracing, optogenetic slice recordings, and somatosensory phenotyping to understand how trans- synaptic adhesion molecules regulate somatosensory circuit assembly and function.