[PDF][PDF] Loss of inhibitory interneurons in the dorsal spinal cord and elevated itch in Bhlhb5 mutant mice

SE Ross, AR Mardinly, AE McCord, J Zurawski… - Neuron, 2010 - cell.com
SE Ross, AR Mardinly, AE McCord, J Zurawski, S Cohen, C Jung, L Hu, SI Mok, A Shah…
Neuron, 2010cell.com
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 …
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.
cell.com