November 28, 2020

The neurokinin-1 receptor is expressed with gastrin-releasing peptide receptor in spinal interneurons and modulates itch

The neurokinin-1 receptor (NK1R, encoded by Tacr1) is expressed in spinal dorsal horn neurons and has been suggested to mediate itch. However, previous studies relied heavily on neurotoxic ablation of NK1R spinal neurons, which limited further dissection of their function in spinal itch circuitry. Thus, we leveraged a newly developed Tacr1CreER mouse line to characterize the role of NK1R spinal neurons in itch. We show that pharmacological activation of spinal NK1R and chemogenetic activation of Tacr1CreER spinal neurons increases itch behavior, whereas pharmacological inhibition of spinal NK1R suppresses itch behavior. We use fluorescence in situ hybridization to characterize the endogenous expression of Tacr1 throughout the superficial and deeper dorsal horn, as well as the lateral spinal nucleus. Retrograde labeling studies from the parabrachial nucleus show that less than 20% of superficial Tacr1CreER dorsal horn neurons are spinal projection neurons, and thus the majority of Tacr1CreER are local interneurons. We then use a combination of in situ hybridization and ex vivo two-photon Ca2+ imaging of the spinal cord to establish that NK1R and the gastrin-releasing peptide receptor (GRPR) are coexpressed within a subpopulation of excitatory superficial dorsal horn neurons. These findings are the first to describe a role for NK1R interneurons in itch and extend our understanding of the complexities of spinal itch circuitry.

 bioRxiv Subject Collection: Neuroscience

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