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Neuron. 2019 Jan 2;101(1):45-59.e9. doi: 10.1016/j.neuron.2018.11.010. Epub 2018 Dec 13.

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

Author information

1
Institute of Neuroscience, State Key Laboratory of Neuroscience, CAS Center for Excellence in Brain Science & Intelligence Technology, Chinese Academy of Sciences, 320 Yue-Yang Road, Shanghai 200031, China; University of Chinese Academy of Sciences, 19A Yu-quan Road, Beijing 100049, China.
2
Department of Pain Management, State Key Specialty in Pain Medicine, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, China.
3
Institute of Neuroscience, State Key Laboratory of Neuroscience, CAS Center for Excellence in Brain Science & Intelligence Technology, Chinese Academy of Sciences, 320 Yue-Yang Road, Shanghai 200031, China.
4
Institute of Neuroscience, State Key Laboratory of Neuroscience, CAS Center for Excellence in Brain Science & Intelligence Technology, Chinese Academy of Sciences, 320 Yue-Yang Road, Shanghai 200031, China. Electronic address: yangang.sun@ion.ac.cn.

Abstract

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.

KEYWORDS:

GRPR; Tac1; extracellular recording; grooming; itch; optogenetics; periaqueductal gray; rostral ventromedial medulla; somatostatin; spinal cord

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