Peripheral gate in somatosensory system (360G-Wellcome-212302_Z_18_Z)

Peripheral nerves are responsible for haptic, somatic and visceral sensations including that of pain. Healthy nerves conduct action potentials from their peripheral endings to the dorsal spinal cord, where synaptic transmission first takes place. It is assumed that the peripheral somatosensory signals are first integrated in the spinal cord and subsequently analysed in the brain. Our recent findings has challenged this view and suggested that peripheral somatosensory ganglia (such as dorsal root ganglia, DRG) are capable to regulate pain transmission utilising GABAergic somatic cross-talk mechanisms. I hypothesize that somatosensory ganglia represent a new type of a ‘gate’ within the somatosensory system. My overarching goal is to develop a comprehensive mechanistic understanding of the peripheral somatosensory gating. I will use in vivo electrophysiology, mouse transgenics, chemo- and optogenetics, behavioural models and other cutting-edge approaches to address the following specific aims. (1) Secure direct in vivo evidence for peripheral somatosensory integration at the DRG. (2) Moving beyond GABA: identify other major ganglionic communication mechanisms. (3) Elucidate physiological context of signal integration in the DRG. (4) Identify subcellular structures involved in somatic integration. These studies will change current understanding of somatosensory processing and will provide new ideas for pain treatment at the periphery.