Genetic Dissection of Direct and Indirect Touch Pathways

Harvard Medical School, Boston MA

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Abstract

? DESCRIPTION (provided by applicant): Sensations such as touch, pain, and itch are encoded across a remarkable diversity of dorsal root ganglia neurons that innervate the skin, yet little is known about how spinal and brainstem recipient neurons integrate these signals. Barriers to a better understanding of peripheral integration include an inability to selectively and efficiently visualize of manipulate specific populations of sensory neurons, and a lack of methods to measure the activity of spinal and brainstem neurons in vivo. The broad goal of this research proposal is to use novel mouse genetic tools in combination with multiphoton functional imaging to gain insight into the functional molecular-genetic approach to selectively label each of the three major subpopulations of low-threshold mechanoreceptive neurons that comprise the direct touch pathway in mice, as well as the spinal neurons that indirectly convey touch information from the spinal cord to the brainstem. To efficiently assess the contributions of these pathways to touch encoding with high spatiotemporal resolution, we will use these genetic tools to silence individual components of the direct pathway and the indirect pathway while imaging populations of second-order neurons in the dorsal column nuclei. Together, this work integration of direct and indirect peripheral touch pathways. First, we will take a will develop novel tools for studying peripheral sensory integration and define cellular and circuit mechanisms that shape touch encoding. Because touch sensation is often disrupted or altered in injury and disease, future work will inform efforts to develop sensory prosthetics and treat the allodynia and hyperalgesia observed in chronic pain states.