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

被引：335

作者：

Ross, Sarah E. ^{[1
]}

Mardinly, Alan R. ^{[1
]}

McCord, Alejandra E. ^{[1
]}

Zurawski, Jonathan ^{[1
]}

Cohen, Sonia ^{[1
,4
]}

Jung, Cynthia ^{[2
,3
]}

Hu, Linda ^{[1
]}

Mok, Stephanie I. ^{[1
]}

Shah, Anar ^{[1
]}

Savner, Erin M. ^{[1
]}

Tolias, Christos ^{[1
]}

Corfas, Roman ^{[1
]}

Chen, Suzhen

Inquimbert, Perrine ^{[4
]}

Xu, Yi ^{[5
]}

McInnes, Roderick R. ^{[2
,3
,6
,7
,8
]}

Rice, Frank L. ^{[9
,10
]}

Corfas, Gabriel ^{[4
]}

Ma, Qiufu ^{[1
,5
]}

Woolf, Clifford J. ^{[1
,4
]}

Greenberg, Michael E. ^{[1
]}

机构：

[1] Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02115 USA

[2] Hosp Sick Children, Res Inst, Program Dev Biol, Toronto, ON M5G 1L7, Canada

[3] Hosp Sick Children, Res Inst, Genet Program, Toronto, ON M5G 1L7, Canada

[4] Childrens Hosp, Dept Neurol, FM Kirby Neurobiol Ctr, Boston, MA 02115 USA

[5] Dana Farber Canc Inst, Boston, MA 02115 USA

[6] Univ Toronto, Dept Mol Genet, Toronto, ON M5S 1A1, Canada

[7] Univ Toronto, Dept Pediat, Toronto, ON M5S 1A1, Canada

[8] Univ Toronto, Inst Med Sci, Toronto, ON M5S 1A1, Canada

[9] Albany Med Coll, Ctr Neuropharmacol Neurosci, Albany, NY 12208 USA

[10] Integrated Tissue Dynam LL, Rensselaer, NY 12144 USA

来源：

NEURON | 2010年 / 65卷 / 06期

关键词：

CENTRAL SENSITIZATION; GABAERGIC INHIBITION; SCRATCHING BEHAVIOR; FORMALIN TEST; PAIN; NEURONS; RESPONSES; HORN; SPECIFICATION; EXPRESSION;

D O I：

10.1016/j.neuron.2010.02.025

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

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.

引用

页码：886 / 898

页数：13

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