Itch is an unpleasant sensation that urges people and animals to scratch.Neuroimaging studies on itch have yielded extensive correlations with diverse cortical and subcortical regions,including the insular lobe.Howeve...Itch is an unpleasant sensation that urges people and animals to scratch.Neuroimaging studies on itch have yielded extensive correlations with diverse cortical and subcortical regions,including the insular lobe.However,the role and functional specificity of the insular cortex(IC)and its subdivisions in itch mediation remains unclear.Here,we demonstrated by immunohistochemistry and fiber photometry tests,that neurons in both the anterior insular cortex(AIC)and the posterior insular cortex(PIC)are activated during acute itch processes.Pharmacogenetic experiments revealed that nonselective inhibition of global AIC neurons,or selective inhibition of the activity of glutaminergic neurons in the AIC,reduced the scratching behaviors induced by intradermal injection of 5-hydroxytryptamine(5-HT),but not those induced by compound 48/80.However,both nonselective inhibition of global PIC neurons and selective inhibition of glutaminergic neurons in the PIC failed to affect the itching-scratching behaviors induced by either 5-HT or compound 48/80.In addition,pharmacogenetic inhibition of AIC glutaminergic neurons effectively blocked itch-associated conditioned place aversion behavior,and inhibition of AIC glutaminergic neurons projecting to the prelimbic cortex significantly suppressed 5-HT-evoked scratching.These findings provide preliminary evidence that the AIC is involved,at least partially via aversive emotion mediation,in the regulation of 5-HT-,but not compound 48/80-induced itch.展开更多
基金supported by the National Natural Science Foundation of China(82271542)the Natural Science Foundation of Chongqing(cstc2020jcyj-msxm X0391 and cstc2019jcyj-msxm X0269)the Chongqing Medical Scientific Research Project(Joint project of Chongqing Health Commission and Science and Technology Bureau)(2023ZDXM001).
文摘Itch is an unpleasant sensation that urges people and animals to scratch.Neuroimaging studies on itch have yielded extensive correlations with diverse cortical and subcortical regions,including the insular lobe.However,the role and functional specificity of the insular cortex(IC)and its subdivisions in itch mediation remains unclear.Here,we demonstrated by immunohistochemistry and fiber photometry tests,that neurons in both the anterior insular cortex(AIC)and the posterior insular cortex(PIC)are activated during acute itch processes.Pharmacogenetic experiments revealed that nonselective inhibition of global AIC neurons,or selective inhibition of the activity of glutaminergic neurons in the AIC,reduced the scratching behaviors induced by intradermal injection of 5-hydroxytryptamine(5-HT),but not those induced by compound 48/80.However,both nonselective inhibition of global PIC neurons and selective inhibition of glutaminergic neurons in the PIC failed to affect the itching-scratching behaviors induced by either 5-HT or compound 48/80.In addition,pharmacogenetic inhibition of AIC glutaminergic neurons effectively blocked itch-associated conditioned place aversion behavior,and inhibition of AIC glutaminergic neurons projecting to the prelimbic cortex significantly suppressed 5-HT-evoked scratching.These findings provide preliminary evidence that the AIC is involved,at least partially via aversive emotion mediation,in the regulation of 5-HT-,but not compound 48/80-induced itch.