Mechanotransduction is the conversion of mechanical force into a cellular response. Many physiological processes involve mechanotransduction such as touch, pain, hearing and balance. Touch receptors are sensory neurons with their cell somas in the dorsal root and trigeminal ganglia and their axons innervating somatic tissues, like the skin. Sensory information is sent to the central nervous system but transduction is far removed from the soma. Due to this anatomy, direct study of mechanotransduction in situ has not yet been possible. Here we will clarify the physiological basis of the mechanotransduction by using a novel experimental approach to overcome these technical limitations. We will set-up an electrophysiological preparation in which the site of transduction is close enough to the ganglion cell body to measure intracellularly single-cell responses to mechanical stimulation. We will dissect out mouse DRG neurons and transplant them into the skin of a host mouse. After innervation of the host skin, skin innervated by transplanted sensory neurons will be prepared and mechanotransduction currents in the transplanted neurons will be recorded using the patch-clamp technique. We will be able, therefore, to stimulate mechanoreceptors with their endings embedded in the skin as occurs in vivo, while recorded from the cell soma. For the first time, we will measure the electrophysiological properties of mechanosensitive ion channels upon physiological stimulation as well as the firing properties of the same mechanoreceptors in current clamp mode. Moreover, using genetically-labeled DRG neurons, we will be able to examine mechanotransduction in different classes of mechanoreceptors or nociceptors. Moreover, given that pain is often evoked by light touch under neuropathic conditions our results will also clarify the physiological mechanisms of transduction of painful sensation, raising the possibility of testing novel methods and drugs to treat sensory disorders.
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