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

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

doi:10.1016/j.neuron.2010.02.025

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

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. WoolfMichael E. Greenberg

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361 Scopus citations

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

Original language	English
Pages (from-to)	886-898
Number of pages	13
Journal	Neuron
Volume	65
Issue number	6
DOIs	https://doi.org/10.1016/j.neuron.2010.02.025
State	Published - Mar 2010
Externally published	Yes

Keywords

Devbio
Molneuro

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10.1016/j.neuron.2010.02.025

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Ross, S. E., Mardinly, A. R., McCord, A. E., Zurawski, J., Cohen, S., Jung, C., Hu, L., Mok, S. I., Shah, A., Savner, E. M., Tolias, C., Corfas, R., Chen, S., Inquimbert, P., Xu, Y., McInnes, R. R., Rice, F. L., Corfas, G., Ma, Q., ... Greenberg, M. E. (2010). Loss of Inhibitory Interneurons in the Dorsal Spinal Cord and Elevated Itch in Bhlhb5 Mutant Mice. Neuron, 65(6), 886-898. https://doi.org/10.1016/j.neuron.2010.02.025

@article{30c629ae0ca44bc8a861c6703135bf0f,

title = "Loss of Inhibitory Interneurons in the Dorsal Spinal Cord and Elevated Itch in Bhlhb5 Mutant Mice",

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

keywords = "Devbio, Molneuro",

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

note = "Funding Information: We thank E.C. Griffith for critical readings of the manuscript; D. Harmin for help with statistical analysis; M. Gee and P. Zhang for assistance with mouse colony management; the MRDDRC Gene Manipulation Core (M. Thompson, Y. Zhou, and H. Ye); the MRDDRC Imaging Core (L. Bu); and the MRDDRC Histology Core (M. Liana). This work was supported by a Jane Coffin Childs Fellowship and a Dystonia Medical Research Foundation Fellowship to S.E.R., NIH grant R01-NS-028829 to M.E.G., and the Developmental Disabilities Mental Retardation Research Center grant NIH-P30-HD-18655 for core support. ",

year = "2010",

month = mar,

doi = "10.1016/j.neuron.2010.02.025",

language = "English",

volume = "65",

pages = "886--898",

journal = "Neuron",

issn = "0896-6273",

publisher = "Cell Press",

number = "6",

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Ross, SE, Mardinly, AR, McCord, AE, Zurawski, J, Cohen, S, Jung, C, Hu, L, Mok, SI, Shah, A, Savner, EM, Tolias, C, Corfas, R, Chen, S, Inquimbert, P, Xu, Y, McInnes, RR, Rice, FL, Corfas, G, Ma, Q, Woolf, CJ & Greenberg, ME 2010, 'Loss of Inhibitory Interneurons in the Dorsal Spinal Cord and Elevated Itch in Bhlhb5 Mutant Mice', Neuron, vol. 65, no. 6, pp. 886-898. https://doi.org/10.1016/j.neuron.2010.02.025

TY - JOUR

T1 - Loss of Inhibitory Interneurons in the Dorsal Spinal Cord and Elevated Itch in Bhlhb5 Mutant Mice

AU - Ross, Sarah E.

AU - Mardinly, Alan R.

AU - McCord, Alejandra E.

AU - Zurawski, Jonathan

AU - Cohen, Sonia

AU - Jung, Cynthia

AU - Hu, Linda

AU - Mok, Stephanie I.

AU - Shah, Anar

AU - Savner, Erin M.

AU - Tolias, Christos

AU - Corfas, Roman

AU - Chen, Suzhen

AU - Inquimbert, Perrine

AU - Xu, Yi

AU - McInnes, Roderick R.

AU - Rice, Frank L.

AU - Corfas, Gabriel

AU - Ma, Qiufu

AU - Woolf, Clifford J.

AU - Greenberg, Michael E.

N1 - Funding Information: We thank E.C. Griffith for critical readings of the manuscript; D. Harmin for help with statistical analysis; M. Gee and P. Zhang for assistance with mouse colony management; the MRDDRC Gene Manipulation Core (M. Thompson, Y. Zhou, and H. Ye); the MRDDRC Imaging Core (L. Bu); and the MRDDRC Histology Core (M. Liana). This work was supported by a Jane Coffin Childs Fellowship and a Dystonia Medical Research Foundation Fellowship to S.E.R., NIH grant R01-NS-028829 to M.E.G., and the Developmental Disabilities Mental Retardation Research Center grant NIH-P30-HD-18655 for core support.

PY - 2010/3

Y1 - 2010/3

N2 - 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.

AB - 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.

KW - Devbio

KW - Molneuro

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U2 - 10.1016/j.neuron.2010.02.025

DO - 10.1016/j.neuron.2010.02.025

M3 - Article

C2 - 20346763

AN - SCOPUS:77950218258

SN - 0896-6273

VL - 65

SP - 886

EP - 898

JO - Neuron

JF - Neuron

IS - 6

ER -

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

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