Conclusion
Our study clarifies the plasticity of Y1Rs on Tac2 neurons during chronic itch and further elucidates the mechanism by which NPY-Y1R system is responsible for modulating mechanical itch. We highlight Y1Rs as a promising therapeutic target for mechanical hyperknesis during chronic itch.
Methods
We combined transgenic mice, chemogenetic manipulation, immunofluorescence, rabies virus circuit tracing, and electrophysiology to investigate the plasticity of Y1Rs on Tac2 neurons during chronic itch.
Results
We found that Tac2 neurons receive direct input from Npy neurons and that inhibition of Npy neurons induces activation of Tac2 neurons. Moreover, the expression of Y1Rs on Tac2 neurons is reduced, and the regulatory effect is also reduced during chronic itch.