A team of scientists led by Dr. Hu Ji from ShanghaiTech’s SLST and Shanghai Jiao Tong University School of Medicine’s Dr. Xu Tian-le has discovered a new mechanism of itch processing.
Itching is an interesting experience consisting of two seemingly opposing components: pruritogen-induced aversion and scratching-induced hedonic feelings. In this study, the joint research team reported on the midbrain circuit mechanisms underlying the unstoppable itch-scratch cycles. They first described differential activation patterns and functions of GABAergic (GABA) and dopaminergic (DA) neurons in the ventral tegmental area (VTA) in the complex itch experience. Then, they applied fiber photometry to demonstrate that VTA GABA and DA neurons were activated with different temporal patterns during itching. The activation of DA neurons lags behind that of GABA neurons for several seconds and is dependent on actual scratching of the itchy site.
Next, optogenetic manipulations and behavioral tests show that VTA GABA neurons rapidly modulate itch-motivated scratching behaviors as well as itch-associated emotional aversion, consistent with their roles in encoding aversive component of itch and initiating scratching. However, VTA DA neurons were shown to mainly promote and sustain recurrent scratching episodes through encoding reward caused by scratching-induced relief of itch, thus indicating cell-type-specific differential involvement of VTA neurons in different aspects of itch processing. Finally, the authors revealed a similar dichotomy regarding engagement of VTA GABA and DA neurons in chronic itch. This study will advance understanding of circuit mechanisms of the unstoppable itch-scratch cycles and shed important insights into chronic itch therapy.
Figure Hypothetic model of the role of different VTA neuronal types in the itch-scratch cycle.