Role of non-coding RNAs in the development of the somatosensory systems

The dorsal horn (DH) of the spinal cord, as part of the central nervous system, is a complex network of neurons whose purpose is to respond and process afferent sensory information conveyed to it from the peripheral nervous system. The DH is a layered (laminated) structure, much like the cerebral cortex, with each lamina receiving different sensory inputs. Neurons in each lamina are also highly heterogenous, some are interneurons conveying information to the brain, others are interneurons relaying information from site to site within the DH.
The way in which the spinal cord matures is central to our experience of pain and our interactions with the environment for the rest of our lives. Pain processing in early life is different to how we experience it as adults, and in large part that is because significant changes in the anatomy and physiology of the DH are still to take place. Crucially sensory neurons undergo significant rearrangement of termination zones in the DH with some neurons extending axons into new DH layers and others retracting or undergoing apoptosis. Painful experiences in early life change the trajectory of these processes and fundamentally alter how we experience pain for the rest of our lives, leaving us with sensory abnormalities and susceptibility to neurological disease.
We wish to understand the processes which control the normal maturation of these circuits and how damage can alter them. We have a strong interest and track-record in the role of miRNA in controlling neuronal behaviour and development and this project will apply our skills and expertise to this problem. Our aim is to identify miRNAs which are central to neurodevelopment and whose function in altered by damage, which in turn feeds onto alterations in neuronal function. These pathways can then be exploited to protect the individual from deleterious consequences of pain in early life.