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Loss of Inhibitory Interneurons in the Dorsal Spinal Cord and Elevated Itch in Bhlhb5 Mutant Mice

2010; Cell Press; Volume: 65; Issue: 6 Linguagem: Inglês

10.1016/j.neuron.2010.02.025

1097-4199

Sarah E. Ross, Alan R. Mardinly, Alejandra E. McCord, Jonathan Zurawski, Sonia Cohen, Cynthia C. Jung, Linda Hu, Stephanie Mok, Anar Shah, Erin M. Savner, Christos Tolias, Román A. Corfas, Suzhen Chen, Perrine Inquimbert, Yi Xu, Roderick R. McInnes, Frank L. Rice, Gabriel Corfas, Qiufu Ma, Clifford J. Woolf, Michael E. Greenberg,

Pharmacological Effects of Natural Compounds

Summary Itch is the least well understood of all the somatic senses, and the neural circuits that underlie this sensation are poorly defined. Here we show that the atonal-related transcription factor Bhlhb5 is transiently expressed in the dorsal horn of the developing spinal cord and appears to play a role in the formation and regulation of pruritic (itch) circuits. Mice lacking Bhlhb5 develop self-inflicted skin lesions and show significantly enhanced scratching responses to pruritic agents. Through genetic fate-mapping and conditional ablation, we provide evidence that the pruritic phenotype in Bhlhb5 mutants is due to selective loss of a subset of inhibitory interneurons in the dorsal horn. Our findings suggest that Bhlhb5 is required for the survival of a specific population of inhibitory interneurons that regulate pruritis, and provide evidence that the loss of inhibitory synaptic input results in abnormal itch.