Tac1-Expressing Neurons in the Periaqueductal Gray Facilitate the Itch-Scratching Cycle via Descending Regulation

• Published in: Neuron (Cambridge, Mass.) Vol. 101; no. 1; pp. 45 - 59.e9
• Main Authors: Gao, Zheng-Run, Chen, Wen-Zhen, Liu, Ming-Zhe, Chen, Xiao-Jun, Wan, Li, Zhang, Xin-Yan, Yuan, Lei, Lin, Jun-Kai, Wang, Meng, Zhou, Li, Xu, Xiao-Hong, Sun, Yan-Gang
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 02-01-2019; Elsevier Limited
• Subjects: Animals; Behavior; Data analysis; Experiments; extracellular recording; Gastrin; Gastrin-releasing peptide; Gene Expression; Glutamatergic transmission; Grooming; GRPR; itch; Male; Mice; Mice, Inbred C57BL; Mice, Transgenic; Neurokinin A - biosynthesis; Neurokinin A - genetics; Neurons; Neurons - chemistry; Neurons - metabolism; optogenetics; Pain; periaqueductal gray; Periaqueductal Gray - chemistry; Periaqueductal Gray - metabolism; Periaqueductal gray area; Pruritus - metabolism; Pruritus - pathology; Pyramidal Tracts - chemistry; Pyramidal Tracts - metabolism; Random Allocation; Receptors, Neurokinin-1 - biosynthesis; Receptors, Neurokinin-1 - genetics; rostral ventromedial medulla; Scratching behavior; Signal processing; Skin; Software; somatostatin; Spinal cord; Statistical analysis; Tac1; Tachykinin; Tachykinin receptors; Tachykinins - biosynthesis; Tachykinins - genetics; extracellular recording; itch; somatostatin; optogenetics; grooming; rostral ventromedial medulla; spinal cord; Tac1; GRPR; periaqueductal gray
• ISSN: 0896-6273; 1097-4199
• DOI: 10.1016/j.neuron.2018.11.010

Uncontrollable itch-scratching cycles lead to serious skin damage in patients with chronic itch. However, the neural mechanism promoting the itch-scratching cycle remains elusive. Here, we report that tachykinin 1 (Tac1)-expressing glutamatergic neurons in the lateral and ventrolateral periaqueductal gray (l/vlPAG) facilitate the itch-scratching cycle. We found that l/vlPAG neurons exhibited scratching-behavior-related neural activity and that itch-evoked scratching behavior was impaired after suppressing the activity of l/vlPAG neurons. Furthermore, we showed that the activity of Tac1-expressing glutamatergic neurons in the l/vlPAG was elevated during itch-induced scratching behavior and that ablating or suppressing the activity of these neurons decreased itch-induced scratching behavior. Importantly, activation of Tac1-expressing neurons induced robust spontaneous scratching and grooming behaviors. The scratching behavior evoked by Tac1-expressing neuron activation was suppressed by ablation of spinal neurons expressing gastrin-releasing peptide receptor (GRPR), the key relay neurons for itch. These results suggest that Tac1-expressing neurons in the l/vlPAG promote itch-scratching cycles.
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•Neurons in l/vlPAG exhibit scratching behavior related to neural activities•Ablation of Tac1+ but not SST+ neurons decreases itch-induced scratching behavior•Activation of Tac1+ neurons induces spontaneous scratching and grooming behaviors•l/vlPAG Tac1+ neurons modulate spinal itch processing via a RVM-dependent pathway
Gao et al. demonstrate that Tac1-expressing neurons in the l/vlPAG modulate spinal itch processing via a descending pathway. These neurons represent a critical component in the neural circuit that drives the itch-scratching cycle.