NEUROFASCIA · Neuronal control of fascia

The fascia is the largest tissue in the body, yet most of us never heard of it. This connective tissue delineates the skin, surrounds muscles, and closely envelops all organs. Clinically, it is mainly considered a mechanical barrier separating organs and muscles. But why should a simple barrier be populated with immune cells and receive extensive innervation by sensory and sympathetic neurons? Here we propose that the fascia generates a sensory platform that detects damage to the tissues it envelops and communicates this information to the brain which in turn, initiates corrective programs and modulates immune activity. Our preliminary results support this hypothesis indicating that chronic depression in mice and direct optogenetic activation of sympathetic fascia innervations induce immune changes in the fascia. We propose three major aims:A)Characterization: Identify the anatomical and genetic characteristics of fascia innervation and fascia resident immune cellsB)Function: Determine how fascia inflammation is represented in the brain and how it affects pain responsesC)Modulation: Demonstrate how neural control of the fascia affects this tissue and its immune state My multidisciplinary background uniquely positions me to study this novel aspect of brain-body communication. We will use viral tracing and spatial transcriptomics to characterize the fascia’s innervation; optogenetics to locally control neurons in the fascia; chemogenetics to manipulate brain activity; and high-dimensional immune characterization to establish the immunological outcomes in the fascia. NEUROFASCIA has the potential to transform our understanding of brain-immune communication and open new therapeutic avenues for disease such as myofascial pain syndrome, endometriosis, and fibromyalgia, which are accompanied by low-grade inflammation and altered fascia innervation.