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

Overview

Journal Neuron

Publisher Cell Press

Specialty Neurology

Date 2010 Mar 30

PMID 20346763

Citations 214

Authors

Sarah E Ross

Alan R Mardinly

Alejandra E McCord

Jonathan Zurawski

Sonia Cohen

Cynthia Jung

Linda Hu

Stephanie I Mok

Anar Shah

Erin M Savner

Christos Tolias

Roman Corfas

Suzhen Chen

Perrine Inquimbert

Yi Xu

Roderick R McInnes

Frank L Rice

Gabriel Corfas

Qiufu Ma

Clifford J Woolf

Michael E Greenberg

Affiliations

Soon will be listed here.

Abstract

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 pruritus, and provide evidence that the loss of inhibitory synaptic input results in abnormal itch.

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