Our perception of the external world comes from our senses. The sense of touch or somatic sensation consists of the perception of multiple discrete stimuli including temperature, pain, proprioception and discriminative touch. Specialized neurons within the dorsal root ganglia (DRG) and trigeminal ganglia (TG) sense these diverse stimuli via nerve endings that project to the skin, muscles and the organs of the body, and this information is then transmitted to the brain via the spinal cord. Electrophysiological characterization has shown that these neurons receive and relay information from these diverse stimuli at least in part through subclasses of DRG neurons that convey different perceptual modalities. Only in the last decade have the genes involved in the direct gating of sensory modalities begun to be identified. Many of these genes belong to the Transient Receptor Potential (TRP) family of non-selective cation channels. TRPV1 a detector of noxious stimuli (heat, capsaicin, low/high pH), TRPA1 another sensor of noxious stimuli (burning cold and noxious chemical agonists such as mustard oil and formaldehyde) and TRPM8 a sensor of innocuous cool temperature are primarily expressed in subsets of DRG and TG neurons and function as sensory receptors in vivo.
While there have been recent advancements, very little is known about how somatosensory neurons become specialized during development and how their neuronal circuitry facilitates their ability to transmit specific environmental cues in the adult. We are interested in understanding the mechanism by which sensory information is coded by the peripheral nervous system, and how specific subclass specificity and neuronal circuit assembly occurs during development. In addition, we are working to identify novel sensory receptors for modalities such as mechanosensation, temperature and nociception. These are fundamental neurobiology themes that are relevant to the study of the many forms of chronic pain, which are debilitating to millions of individuals. In addition, discovering how the simple circuits of the peripheral nervous system assemble and code information output will not only help us understand how we perceive the world around us but may also provide valuable insight into how these processes occur in the more complex circuits of the brain.
My lab is taking advantage of the recent identification of molecular markers (TRP channels) that define specific sensory modalities to help further our understanding of sensory perception. To this end, we are using novel tools and techniques that we have developed in combination with mouse genetics, molecular biology, biochemistry and live cell imaging to achieve our goals.
Publications [from PubMed]
- An ancient neurotrophin receptor code; a single Runx/Cbfβ complex determines somatosensory neuron fate specification in zebrafish.Gau P, Curtright A, Condon L, Raible DW, Dhaka APLoS genetics. 2017 Jul; 13 7: e1006884
- The Pore Loop Domain of TRPV1 Is Required for Its Activation by the Volatile Anesthetics Chloroform and Isoflurane.Kimball C, Luo J, Yin S, Hu H, Dhaka AMolecular pharmacology. 2015 Jul; 88 1: 131-8
- Laing RJ, Dhaka AThe Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry. 2016 Apr; 22 2: 171-87
- Curtright A, Rosser M, Goh S, Keown B, Wagner E, Sharifi J, Raible DW, Dhaka APloS one. 2015 ; 10 1: e0116766
- Gau P, Poon J, Ufret-Vincenty C, Snelson CD, Gordon SE, Raible DW, Dhaka AThe Journal of neuroscience : the official journal of the Society for Neuroscience. 2013 Mar; 33 12: 5249-60