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Each day we experience myriad somatosensory stimuli: hugs from loved ones, warm showers, a mosquito bite, and sore muscles after a workout. These tactile, thermal, itch, and nociceptive signals are detected by peripheral sensory neuron terminals distributed throughout our body, propagated into the spinal cord, and then transmitted to the brain through ascending spinal pathways. Primary sensory neurons that detect a wide range of somatosensory stimuli have been identified and characterized. In contrast, very little is known about how peripheral signals are integrated and processed within the spinal cord and conveyed to the brain to generate somatosensory perception and behavioral responses. We tackled this question by developing new mouse genetic tools to define projection neuron (PN) subsets of the anterolateral pathway, a major ascending spinal cord pathway, and combining these new tools with advanced anatomical, physiological, and behavioral approaches. We found that Gpr83+ PNs, a newly identified subset of spinal cord output neurons, and Tacr1+ PNs are largely non-overlapping populations that innervate distinct sets of subnuclei within the lateral parabrachial nucleus (PBNL) of the pons in a zonally segregated manner. In addition, Gpr83+ PNs are highly sensitive to cutaneous mechanical stimuli, receive strong synaptic inputs from primary mechanosensory neurons, and convey tactile information bilaterally to the PBNL in a non-topographically organized manner. Remarkably, Gpr83+ mechanosensory limb of the anterolateral pathway controls behaviors associated with different hedonic values (appetitive or aversive) in a scalable manner. Our study reveals a dedicated spinal cord output pathway that conveys affective touch signals to the brain as well as parallel ascending circuit modules that cooperate to convey tactile, thermal and noxious cutaneous signals from the spinal cord to the brain. Furthermore, our study provides an insight into the new therapeutic opportunities for developing treatments for neurological disorders associated with pain and affective touch. This work was supported by the Alice and Joseph E. Brooks Funds (S.C.), the Blavatnik Biomedical Accelerator Fund (S.C., D.G), NIH grants NS097344 and AT011447 (D.G.), AR063772 (S.R.), NS096705 (H.K.), the Bertarelli Foundation (D.G.), The Hock E. Tan and Lisa Yang Center for Autism Research at Harvard University (D.G.) and the Edward R. and Anne G. Lefler Center for Neurodegenerative Disorders (D.G). D.G. is an investigator of the Howard Hughes Medical Institute.
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